Influenza vaccination
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Influenza vaccines, also known as flu shots, are
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
s that protect against infection by
influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...
viruses. New versions of the vaccines are developed twice a year, as the
influenza virus ''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ' ...
rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. The United States
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
(CDC) estimates that vaccination against influenza reduces sickness, medical visits, hospitalizations, and deaths. Immunized workers who do catch the flu return to work half a day sooner on average. Vaccine effectiveness in those over 65 years old remains uncertain due to a lack of high-quality research. Vaccinating children may protect those around them. Vaccines are an effective means to control outbreaks of many diseases. However, vaccines for respiratory viral infections such as flu are still suboptimal and do not offer broad-spectrum protection. Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(WHO) and the CDC recommend yearly vaccination for nearly all people over the age of six months, especially those at high risk. The European Centre for Disease Prevention and Control (ECDC) also recommends yearly vaccination of high risk groups. These groups include
pregnant Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
women, the elderly, children between six months and five years of age, and those with certain health problems. The vaccines are generally safe, including for people who have severe
egg allergies Egg allergy is an immune hypersensitivity to proteins found in chicken eggs, and possibly goose, duck, or turkey eggs. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anaph ...
.
Fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
occurs in five to ten percent of children vaccinated, and temporary muscle pains or feelings of tiredness may occur. In certain years, the vaccine was linked to an increase in
Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain oft ...
among older people at a rate of about one case per million doses. Influenza vaccines are not recommended in those who have had a severe allergy to previous versions of the vaccine itself. The vaccine comes in '' inactive'' and '' weakened'' viral forms. The live, weakened vaccine is generally not recommended in pregnant women, children less than two years old, adults older than 50, or people with a weakened immune system. Depending on the type they can be injected into a muscle, sprayed into the nose, or injected into the middle layer of the skin (intradermal). The intradermal vaccine was not available during the 2018–2019 and 2019–2020 influenza seasons.


History

Vaccines are used in both humans and nonhumans. Human vaccine is meant unless specifically identified as a veterinary, poultry or livestock vaccine.


Origins and development

In the worldwide
Spanish flu The 1918–1920 influenza pandemic, commonly known by the misnomer Spanish flu or as the Great Influenza epidemic, was an exceptionally deadly global influenza pandemic caused by the H1N1 influenza A virus. The earliest documented case wa ...
pandemic of 1918, "Pharmacists tried everything they knew, everything they had ever heard of, from the ancient art of
bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
patients, to administering oxygen, to developing new vaccines and serums (chiefly against what we now call '' Hemophilus influenzae''a name derived from the fact that it was originally considered the etiological agentand several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success." In 1931, viral growth in embryonated hens' eggs was reported by Ernest William Goodpasture and colleagues at
Vanderbilt University Vanderbilt University (informally Vandy or VU) is a private research university in Nashville, Tennessee. Founded in 1873, it was named in honor of shipping and rail magnate Cornelius Vanderbilt, who provided the school its initial $1-million ...
. The work was extended to growth of influenza virus by several workers, including Thomas Francis,
Jonas Salk Jonas Edward Salk (; born Jonas Salk; October 28, 1914June 23, 1995) was an American virologist and medical researcher who developed one of the first successful polio vaccines. He was born in New York City and attended the City College of New ...
, Wilson Smith and Macfarlane Burnet, leading to the first experimental influenza vaccines. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used in the Second World War. Hen's eggs continued to be used to produce virus used in influenza vaccines, but manufacturers made improvements in the purity of the virus by developing improved processes to remove egg proteins and to reduce systemic reactivity of the vaccine. In 2012, the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) approved influenza vaccines made by growing virus in
cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This tec ...
s and influenza vaccines made from
recombinant protein Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
s have been approved, with plant-based influenza vaccines being tested in clinical trials.


Acceptance

The egg-based technology for producing influenza vaccine was created in the 1950s. In the US swine flu scare of 1976, President
Gerald Ford Gerald Rudolph Ford Jr. ( ; born Leslie Lynch King Jr.; July 14, 1913December 26, 2006) was an American politician who served as the 38th president of the United States from 1974 to 1977. He was the only president never to have been elected ...
was confronted with a potential swine flu pandemic. The
vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulat ...
program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base, a number of soldiers fell severely ill, but only one died. The program was canceled after about 24% of the population had received vaccinations. An excess in deaths of 25 over normal annual levels as well as 400 excess hospitalizations, both from
Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain oft ...
, were estimated to have occurred from the vaccination program itself, demonstrating that the vaccine itself is not free of risks. The result can be cited to support lingering doubts about vaccination as well as to counter ungrounded claims about the safety of vaccination. In the end, however, even the maligned 1976 vaccine may have saved lives. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976. The 2009 H1N1 “swine flu” outbreak resulted in the rapid approval of pandemic influenza vaccines.
Pandemrix Pandemrix is an influenza vaccine for influenza pandemics, such as the 2009 flu pandemic. The vaccine was developed by GlaxoSmithKline (GSK) and patented in September 2006. The vaccine was one of the H1N1 vaccines approved for use by the Europe ...
was quickly modified to target the circulating strain and by late 2010, 70 million people had received a dose. Eight years later,
the BMJ ''The BMJ'' is a weekly peer-reviewed medical trade journal, published by the trade union the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world's oldest general medical journals. Origi ...
gained access to vaccine pharmacovigilance reports compiled by GSK (GlaxoSmithKline) during the pandemic which the BMJ reported indicated death was 5.39 fold more likely with Pandemrix ''vs'' the other pandemic vaccines..


Quadrivalent vaccines for seasonal flu

A quadrivalent flu vaccine administered by nasal mist was approved by the FDA in March 2012. Fluarix Quadrivalent was approved by the FDA in December 2012. In 2014, the Canadian
National Advisory Committee on Immunization The National Advisory Committee on Immunization (NACI; french: Comité consultatif national de l'immunisation; french: CCNI, label=none) is an advisory body that provides the Government of Canada with medical and scientific advice relating to h ...
(NACI) published a review of quadrivalent influenza vaccines. Starting with the 2018–2019 influenza season most of the regular-dose egg-based flu shots and all the recombinant and cell-grown flu vaccines in the United States are quadrivalent. In the 2019–2020 influenza season all regular-dose flu shots and all recombinant influenza vaccine in the United States are quadrivalent. In November 2019, the FDA approved Fluzone High-Dose Quadrivalent for use in the United States starting with the 2020–2021 influenza season. In February 2020, the FDA approved Fluad Quadrivalent for use in the United States. In July 2020, the FDA approved both Fluad and Fluad Quadrivalent for use in the United States for the 2020–2021 influenza season.


Medical uses

The U.S
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
(CDC) recommends the flu vaccine as the best way to protect people against the flu and prevent its spread. The flu vaccine can also reduce the severity of the flu if a person contracts a strain that the vaccine did not contain. It takes about two weeks following vaccination for protective
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
to form. A 2012
meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting m ...
found that flu vaccination was effective 67percent of the time; the populations that benefited the most were
HIV-positive The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immun ...
adults aged 18 to 55 (76percent), healthy adults aged 18 to 46 (approximately 70percent), and healthy children aged six months to 24 months (66percent). The influenza vaccine also appears to protect against
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
with a benefit of 15–45%.


Effectiveness

A vaccine is assessed by its ''efficacy'' – the extent to which it reduces risk of disease under controlled conditions – and its ''effectiveness'' – the observed reduction in risk after the vaccine is put into use. In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of
influenza-like illness Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...
, which is not always caused by influenza. Studies on the effectiveness of flu vaccines in the real world are difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses. However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains, and even a mismatched vaccine can often provide cross-protection. The virus rapidly changes due to antigenic drift, a slight mutation in the virus that causes a new strain to arise. The effectiveness of seasonal flu vaccines varies significantly, with an estimated average efficacy of 50–60% against symptomatic disease, depending on vaccine strain, age, prior immunity, and immune function, so vaccinated people can still contract influenza. The effectiveness of flu vaccines is considered to be suboptimal, particularly among the elderly, but vaccination is still beneficial in reducing the mortality rate and hospitalization rate due to influenza as well as duration of hospitalization. Vaccination of school-age children has shown to provide indirect protection for other age groups. LAIVs are recommended for children based on superior efficacy, especially for children under 6, and greater immunity against non-vaccine strains when compared to inactivated vaccines. From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an
intensive care unit 220px, Intensive care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensi ...
was 82%. Effectiveness against hospitalized influenza illness in the 2019–2020 United States flu season was 41% overall and 54% in people aged 65 years or older. One review found 31% effectiveness against death among adults. Repeated annual influenza vaccination generally offer consistent year-on-year protection against influenza. There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes; this has no relevance to current recommendations for yearly vaccinations but might influence future vaccination policy. , the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination. There is not enough evidence to establish significant differences in the effectiveness of different influenza vaccine types, but there are high-dose or adjuvanted products that induce a stronger immune response in the elderly.


Children

In April 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged that children 6 to 23 months of age be vaccinated annually against influenza. In 2010, ACIP recommended annual influenza vaccination for those 6 months of age and older. Currently the CDC recommends that everyone except
infant An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used t ...
s under the age of six months should receive the seasonal influenza vaccine. Vaccination campaigns usually focus special attention on people who are at high risk of serious complications if they catch the flu, such as pregnant women, children under 59 months, the elderly, and people with
chronic illness A chronic condition is a health condition or disease that is persistent or otherwise long-lasting in its effects or a disease that comes with time. The term ''chronic'' is often applied when the course of the disease lasts for more than three m ...
es or weakened immune systems, as well as those to whom they are exposed, such as health care workers. As the death rate is also high among infants who catch influenza, the CDC and the WHO recommend that household contacts and caregivers of infants be vaccinated to reduce the risk of passing an influenza infection to the infant. In children, the vaccine appears to decrease the risk of influenza and possibly
influenza-like illness Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...
. In children under the age of two data are limited. During the 2017–18 flu season, the CDC director indicated that 85 percent of the children who died "likely will not have been vaccinated". In the United States, , the CDC recommend that children aged six through 35 months may receive either 0.25milliliters or 0.5milliliters per dose of Fluzone Quadrivalent. There is no preference for one or the other dose volume of Fluzone Quadrivalent for that age group. All persons 36 months of age and older should receive 0.5 milliliters per dose of Fluzone Quadrivalent. , Afluria Quadrivalent is licensed for children six months of age and older in the United States. Children six months through 35 months of age should receive 0.25milliliters for each dose of Afluria Quadrivalent. All persons 36 months of age and older should receive 0.5milliliters per dose of Afluria Quadrivalent. , Afluria Tetra is licensed for adults and children five years of age and older in Canada. In 2014, the Canadian
National Advisory Committee on Immunization The National Advisory Committee on Immunization (NACI; french: Comité consultatif national de l'immunisation; french: CCNI, label=none) is an advisory body that provides the Government of Canada with medical and scientific advice relating to h ...
(NACI) published a review of influenza vaccination in healthy 5–18-year-olds, and in 2015, published a review of the use of pediatric Fluad in children 6–72 months of age. In one study, conducted in a tertiary referral center, the rate of influenza vaccination in children was only 31%. Higher rates were found among immuno-suppressed pediatric patients (46%), and in patients with inflammatory bowel disease (50%).


Adults

In unvaccinated adults, 16% get symptoms similar to the flu, while about 10% of vaccinated adults do. Vaccination decreased confirmed cases of influenza from about 2.4% to 1.1%. No effect on hospitalization was found. In working adults, a review by the
Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
found that vaccination resulted in a modest decrease in both influenza symptoms and working days lost, without affecting transmission or influenza-related complications. In healthy working adults, influenza vaccines can provide moderate protection against virologically confirmed influenza, though such protection is greatly reduced or absent in some seasons. In health care workers, a 2006 review found a net benefit. Of the eighteen studies in this review, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of health care worker vaccination correlated with reduced patient deaths. A 2014 review found benefits to patients when health care workers were immunized, as supported by moderate evidence based in part on the observed reduction in all-cause deaths in patients whose health care workers were given immunization compared with comparison patients where the workers were not offered vaccine.


Elderly

Evidence for an effect in adults over 65 is unclear. Systematic reviews examining both randomized controlled and case–control studies found a lack of high-quality evidence. Reviews of case–control studies found effects against laboratory-confirmed influenza,
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
, and death among the community-dwelling elderly. The group most vulnerable to non-pandemic flu, the elderly, benefits least from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age. In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over 65 is more than ten times more likely to die an influenza-associated death than the 50–64 age group. There is a high-dose flu vaccine specifically formulated to provide a stronger immune response. Available evidence indicates that vaccinating the elderly with the high-dose vaccine leads to a stronger immune response against influenza than the regular-dose vaccine. A flu vaccine containing an
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesi ...
was approved by the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the MF59C.1 adjuvant which is an oil-in-water emulsion of squalene oil. It is the first adjuvanted seasonal flu vaccine marketed in the United States. It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant. Per
Advisory Committee on Immunization Practices The Advisory Committee on Immunization Practices (ACIP) is a committee within the United States Centers for Disease Control and Prevention (CDC) that provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. c ...
guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older. Vaccinating health care workers who work with elderly people is recommended in many countries, with the goal of reducing influenza outbreaks in this vulnerable population. While there is no conclusive evidence from
randomized clinical trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
s that vaccinating health care workers helps protect elderly people from influenza, there is tentative evidence of benefit. Fluad Quad was approved for use in Australia in September 2019, Fluad Quadrivalent was approved for use in the United States in February 2020, and Fluad Tetra was approved for use in the European Union in May 2020.


Pregnancy

As well as protecting mother and child from the effects of an influenza infection, the immunization of pregnant women tends to increase their chances of experiencing a successful full-term pregnancy. The trivalent inactivated influenza vaccine is protective in pregnant women infected with HIV.


Safety


Side effects

Common side effects of vaccination include local injection-site reactions and
cold Cold is the presence of low temperature, especially in the atmosphere. In common usage, cold is often a subjective perception. A lower bound to temperature is absolute zero, defined as 0.00K on the Kelvin scale, an absolute thermodynamic ...
-like symptoms. Fever, malaise, and myalgia are less common. Flu vaccines are
contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...
for people who have experienced a severe allergic reaction in response to a flu vaccine or to any component of the vaccine. LAIVs are not given to children or adolescents with severe immunodeficiency or to those who are using salicylate treatments because of the risk of developing
Reye syndrome Reye syndrome is a rapidly worsening brain disease. Symptoms of Reye syndrome may include vomiting, personality changes, confusion, seizures, and loss of consciousness. While liver toxicity typically occurs in the syndrome, jaundice usually doe ...
. LAIVs are also not recommended for children under the age of 2, pregnant women, and adults with immunosuppression. Inactivated flu vaccines cannot cause influenza and are regarded as safe during pregnancy. While side effects of the flu vaccine may occur, they are usually minor, including soreness, redness, and swelling around the point of injection, headache, fever, nausea or fatigue. Side effects of a nasal spray vaccine may include runny nose, wheezing, sore throat, cough, or vomiting. In some people, a flu vaccine may cause serious side effects, including an
allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
, but this is rare. Furthermore, the common side effects and risks are mild and temporary when compared to the risks and severe health effects of the annual
influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...
epidemic.


Guillain–Barré syndrome

Although
Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain oft ...
had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain–Barré. Infection with influenza virus itself increases both the risk of death (up to one in ten thousand) and the risk of developing Guillain–Barré syndrome to a far higher level than the highest level of suspected vaccine involvement (approximately ten times higher by 2009 estimates). Although one review gives an incidence of about one case of Guillain–Barré per million vaccinations, a large study in China, covering close to a hundred million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain–Barré syndrome, (0.1 per million doses) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects.


Egg allergy

Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless still recommended as safe for people with
egg allergies Egg allergy is an immune hypersensitivity to proteins found in chicken eggs, and possibly goose, duck, or turkey eggs. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anaph ...
, even if severe, as no increased risk of allergic reaction to the egg-based vaccines has been shown for people with egg allergies. Studies examining the safety of influenza vaccines in people with severe egg allergies found that
anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...
was very rare, occurring in 1.3 cases per million doses given. Monitoring for symptoms from vaccination is recommended in those with more severe symptoms. A study of nearly 800 children with egg allergy, including over 250 with previous anaphylactic reactions, had zero systemic allergic reactions when given the live attenuated flu vaccine. Vaccines produced using other technologies, notably recombinant vaccines and those based on cell culture rather than egg protein, started to become available from 2012 in the US, and later in Europe and Australia.


Other

Several studies have identified an increased incidence of
narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...
among recipients of the pandemic H1N1 influenza
AS03 AS03 (for "Adjuvant System 03") is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline (GSK). It is used, for example, in GSK's A/H1N1 pandemic flu vaccine Pandemrix. It is also in Arepanrix ...
-adjuvanted vaccine; efforts to identify a mechanism for this suggest that narcolepsy is autoimmune, and that the AS03-adjuvanted H1N1 vaccine may mimic hypocretin, serving as a trigger. Some injection-based flu vaccines intended for adults in the United States contain
thiomersal Thiomersal (INN), or thimerosal (USAN, JAN), is an organomercury compound. It is a well-established antiseptic and antifungal agent. The pharmaceutical corporation Eli Lilly and Company gave thiomersal the trade name Merthiolate. It has been u ...
(also known as thimerosal), a mercury-based preservative. Despite some
controversy Controversy is a state of prolonged public dispute or debate, usually concerning a matter of conflicting opinion or point of view. The word was coined from the Latin ''controversia'', as a composite of ''controversus'' – "turned in an opposite d ...
in the media, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
's Global Advisory Committee on Vaccine Safety has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration.


Types

Flu vaccines are available either as: * a trivalent or quadrivalent intramuscular injection (IIV3, IIV4, or RIV4, that is, TIV or QIV), which contains the inactivated form of the virus * a nasal spray of
live attenuated influenza vaccine Live attenuated influenza vaccine (LAIV) is a type of influenza vaccine in the form of a nasal spray that is recommended for the prevention of influenza. It is an attenuated vaccine, unlike most influenza vaccines, which are inactivated vacci ...
(LAIV, Q/LAIV), which contains the live but attenuated (weakened) form of the virus. TIV or QIV induce protection after injection (typically intramuscular, though subcutaneous and intradermal routes can also be protective) based on an
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which coul ...
to the antigens present on the inactivated virus, while cold-adapted LAIV works by establishing infection in the nasal passages.


Recommendations

Various public health organizations, including the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(WHO), recommend that yearly influenza vaccination be routinely offered, particularly to people at risk of complications of influenza and those individuals who live with or care for high-risk individuals, including: * people aged 50 years of age or older * people with chronic lung diseases, including
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
* people with chronic heart diseases * people with chronic liver diseases * people with chronic kidney diseases * people who have had their
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
removed or whose spleen is not working properly * people who are immunocompromised * residents of nursing homes and other long-term care facilities * health care workers (both to prevent sickness and to prevent spread to their patients) * * children and adolescents (aged 6 months through 18 years) who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection * American Indians/Alaska Natives * people who are extremely obese (body mass index ≥40 for adults) The flu vaccine is contraindicated for those under six months of age and those with severe, life-threatening allergies to flu vaccine or any ingredient in the vaccine.


World Health Organization

, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(WHO) recommends seasonal influenza vaccination for: ''First priority:'' * Pregnant women ''Second priority (in no particular order):'' * Children aged 6–59 months * Elderly * Individuals with specific chronic medical conditions * Health-care workers


Canada

The National Advisory Committee on Immunization (NACI), the group that advises the
Public Health Agency of Canada The Public Health Agency of Canada (PHAC; french: Agence de la santé publique du Canada, ASPC) is an agency of the Government of Canada that is responsible for public health, emergency preparedness and response, and infectious and chronic dis ...
, recommends that everyone over six months of age be encouraged to receive annual influenza vaccination, and that children between the age of six months and 24 months, and their household contacts, should be considered a high priority for the flu vaccine. Particularly: * People at high risk of influenza-related complications or hospitalization, including people who are morbidly obese, healthy pregnant women, children aged 6–59 months, the elderly, aboriginals, and people with one of an itemized list of chronic health conditions * People capable of transmitting influenza to those at high risk, including household contacts and health care workers * People who provide essential community services * Certain poultry workers Live attenuated influenza vaccine (LAIV) was not available in Canada for the 2019–2020 season.


European Union

The European Centre for Disease Prevention and Control (ECDC) recommends vaccinating the elderly as a priority, with a secondary priority people with chronic medical conditions and health care workers. The influenza vaccination strategy is generally that of protecting vulnerable people, rather than limiting influenza circulation or eliminating human influenza sickness. This is in contrast with the high
herd immunity Herd immunity (also called herd effect, community immunity, population immunity, or mass immunity) is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become im ...
strategies for other infectious diseases such as
polio Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe sy ...
and
measles Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...
. This is also due in part to the financial and logistics burden associated with the need of an annual injection.


United States

In the United States routine influenza vaccination is recommended for all persons aged six months and over. It takes up to two weeks after vaccination for sufficient antibodies to develop in the body. The CDC recommends vaccination before the end of October, although it considers getting a vaccine in December or even later to be still beneficial. According to the CDC, the live attenuated virus (LAIV4) (which comes in the form of the nasal spray in the US) should be avoided by some groups. Within its blanket recommendation for general vaccination in the United States, the CDC, which began recommending the influenza vaccine to health care workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their
caregivers A caregiver or carer is a paid or unpaid member of a person's social network who helps them with activities of daily living. Since they have no specific professional training, they are often described as informal caregivers. Caregivers most commo ...
: :Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications. In 2009, a new high-dose formulation of the standard influenza vaccine was approved. The Fluzone High Dose is specifically for people 65 and older; the difference is that it has four times the antigen dose of the standard Fluzone. The US government requires hospitals to report worker vaccination rates. Some US states and hundreds of US hospitals require health care workers to either get vaccinations or wear masks during flu season. These requirements occasionally engender union lawsuits on narrow
collective bargaining Collective bargaining is a process of negotiation between employers and a group of employees aimed at agreements to regulate working salaries, working conditions, benefits, and other aspects of workers' compensation and rights for workers. The ...
grounds, but proponents note that courts have generally endorsed forced vaccination laws affecting the general population during disease outbreaks. Vaccination against influenza is especially considered important for members of high-risk groups who would be likely to have complications from influenza, for example pregnant women and children and teenagers from six months to 18 years of age who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection; * In raising the upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications * An added benefit expected from the vaccination of children is a reduction in the number of influenza cases among parents and other household members, and of possible spread to the general community. The CDC indicated that
live attenuated influenza vaccine Live attenuated influenza vaccine (LAIV) is a type of influenza vaccine in the form of a nasal spray that is recommended for the prevention of influenza. It is an attenuated vaccine, unlike most influenza vaccines, which are inactivated vacci ...
(LAIV), also called the nasal spray vaccine, was not recommended for the 2016–2017 flu season in the United States. Furthermore, the CDC recommends that health care personnel who care for severely immunocompromised persons receive injections (TIV or QIV) rather than LAIV.


United Kingdom

Dr
Jenny Harries Dame Jennifer Margaret Harries is a British public health physician who has been the chief executive of the UK Health Security Agency and head of NHS Test and Trace since April 2021. She was previously a regional director at Public Health En ...
maintained winter 2021–2022 in the UK will be "uncertain" since flu and
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quick ...
will be circulating together for the first time. She urged eligible people to get
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quick ...
and flu vaccines. She maintains flu vaccination is important every year. People need to know that flu can be fatal as many people do not know this.


Australia

The
Australian Government The Australian Government, also known as the Commonwealth Government, is the national government of Australia, a federal parliamentary constitutional monarchy. Like other Westminster-style systems of government, the Australian Governmen ...
recommends seasonal flu vaccination for everyone over the age of six months. Australia uses
inactivated vaccine An inactivated vaccine (or killed vaccine) is a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed to destroy disease-producing capacity. In contrast, live vaccines use pathogens ...
s. Until 2021, the egg-based vaccine has been the only one available (and continues to be the only free one), but from March 2021 a new cell-based vaccine is available for those who wish to pay for it, and it is expected that this one will become the standard by 2026. The standard flu vaccine is free for the following people: * children aged six months to five years; * people aged 65 years and over; * Aboriginal and Torres Strait Islander people aged six months and over; * pregnant women; and * anyone over six months of age with medical conditions such as severe asthma, lung disease or heart disease, low immunity or diabetes that can lead to complications from influenza.


Uptake


At risk groups

Uptake of flu vaccination, both seasonally and during pandemics, is often low. Systematic reviews of pandemic flu vaccination uptake have identified several personal factors that may influence uptake, including gender (higher uptake in men), ethnicity (higher in people from ethnic minorities) and having a chronic illness. Beliefs in the safety and effectiveness of the vaccine are also important. A number of measures have been found to be useful to increase rates of vaccination in those over sixty including: patient reminders using leaflets and letters, postcard reminders, client outreach programs, vaccine home visits, group vaccinations, free vaccinations, physician payment, physician reminders and encouraging physician competition.


Health care workers

Frontline health care workers are often recommended to get seasonal and any pandemic flu vaccination. For example, in the UK all health care workers involved in patient care are recommended to receive the seasonal flu vaccine, and were also recommended to be vaccinated against the
H1N1/09 The pandemic H1N1/09 virus is a swine origin influenza A virus subtype H1N1 strain that was responsible for the 2009 swine flu pandemic. This strain is often called swine flu by the public media. For other names, see the Nomenclature section ...
(later renamed A(H1N1)pdm09(H1N1)pdm09 is newer nomenclature for the 2009 pandemic H1N1 virus, not a different strain. ) swine flu virus during the 2009 pandemic. However, uptake is often low. During the 2009 pandemic, low uptake by healthcare workers was seen in countries including the UK, Italy, Greece, and Hong Kong. In a 2010 survey of United States health care workers, 63.5% reported that they received the flu vaccine during the 2010–11 season, an increase from 61.9% reported the previous season. US Health professionals with direct patient contact had higher vaccination uptake, such as physicians and dentists (84.2%) and
nurse practitioners A nurse practitioner (NP) is an advanced practice registered nurse and a type of mid-level practitioner. NPs are trained to assess patient needs, order and interpret diagnostic and laboratory tests, diagnose disease, formulate and prescribe ...
(82.6%). The main reason to vaccinate health care workers is to prevent staff from spreading flu to their patients and to reduce staff absence at a time of high service demand, but the reasons health care workers state for their decisions to accept or decline vaccination may more often be to do with perceived personal benefits. In Victoria (Australia) public hospitals, rates of health care worker vaccination in 2005 ranged from 34% for non-clinical staff to 42% for laboratory staff. One of the reasons for rejecting vaccines was concern over adverse reactions; in one study, 31% of resident physicians at a teaching hospital incorrectly believed Australian vaccines could cause influenza.


Manufacturing

Research continues into the idea of a "universal" influenza vaccine that would not require tailoring to a particular strain, but would be effective against a broad variety of influenza viruses. No vaccine candidates had been announced by November 2007, but , there are several universal vaccines candidates, in pre-clinical development and in clinical trials. In a 2007 report, the global capacity of approximately 826 million seasonal influenza vaccine doses (inactivated and live) was double the production of 413 million doses. In an aggressive scenario of producing
pandemic influenza An influenza pandemic is an epidemic of an influenza virus that spreads across a large region (either multiple continents or worldwide) and infects a large proportion of the population. There have been six major influenza epidemics in the las ...
vaccines by 2013, only 2.8 billion courses could be produced in a six-month time frame. If all high- and upper-middle-income countries sought vaccines for their entire populations in a pandemic, nearly two billion courses would be required. If China pursued this goal as well, more than three billion courses would be required to serve these populations. Vaccine research and development is ongoing to identify novel vaccine approaches that could produce much greater quantities of vaccine at a price that is affordable to the global population.


Egg-based

Most flu vaccines are grown by vaccine manufacturers in fertilized
chicken The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adu ...
eggs. In the Northern hemisphere, the manufacturing process begins following the announcement (typically in February) of the WHO recommended strains for the winter flu season. Three strains (representing an H1N1, an H3N2, and a B strain) of flu are selected and chicken eggs are inoculated separately. These monovalent harvests are then combined to make the trivalent vaccine. , both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union also approved Optaflu, a vaccine produced by
Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-lo ...
using vats of animal cells. This technique is expected to be more scalable and avoid problems with eggs, such as allergic reactions and incompatibility with strains that affect avians like chickens. Influenza vaccines are produced in
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
-free eggs that are eleven or twelve days old. The top of the egg is disinfected by wiping it with alcohol and then the egg is candled to identify a non-veinous area in the allantoic cavity where a small hole is poked to serve as a pressure release. A second hole is made at the top of the egg, where the influenza virus is injected in the allantoic cavity, past the chorioallantoic membrane. The two holes are then sealed with melted paraffin and the inoculated eggs are incubated for 48 hours at 37 degrees Celsius. During incubation time, the virus replicates and newly replicated viruses are released into the allantoic fluid After the 48-hour incubation period, the top of the egg is cracked and the ten milliliters of allantoic fluid is removed, from which about fifteen micrograms of the flu vaccine can be obtained. At this point, the viruses have been weakened or killed and the viral antigen is purified and placed inside vials, syringes, or nasal sprayers. Done on a large-scale, this method is used to produce the flu vaccine for the human population.


Other methods of manufacture

Methods of vaccine generation that bypass the need for eggs include the construction of influenza virus-like particles (VLP). VLP resemble viruses, but there is no need for inactivation, as they do not include viral coding elements, but merely present antigens in a similar manner to a virion. Some methods of producing VLP include cultures of '' Spodoptera frugiperda'' Sf9 insect cells and plant-based vaccine production (e.g., production in ''
Nicotiana benthamiana ''Nicotiana benthamiana'', colloquially known as benth or benthi, is a species of ''Nicotiana'' indigenous to Australia. It is a close relative of tobacco. A synonym for this species is ''Nicotiana suaveolens'' var. ''cordifolia'', a descrip ...
''). There is evidence that some VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the hemagglutination-inhibition assay (HIA). A gene-based DNA vaccine, used to prime the immune system after boosting with an inactivated H5N1 vaccine, underwent clinical trials in 2011. On November 20, 2012, Novartis received FDA approval for the first cell-culture vaccine. In 2013, the recombinant influenza vaccine, Flublok, was approved for use in the United States. On September 17, 2020, the
Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regardin ...
(CHMP) of the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Eur ...
(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Supemtek, a quadrivalent influenza vaccine (recombinant, prepared in cell culture). Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is Sanofi Pasteur. Supemtek was approved for medical use in the European Union in November 2020. Australia authorised its first and cell-based vaccine in March 2021, based on an "eternal cell line" of a dog
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
. Because of the way it is produced, it produces better-matched vaccine (to the flu strains).


Vaccine manufacturing countries

According to the WHO, , countries where influenza vaccine is produced include: In addition, Kazakhstan, Serbia and Thailand had facilities in final stages of establishing production.


Cost-effectiveness

The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings. In the elderly (over 65), the majority of published studies have found that vaccination is cost saving, with the cost savings associated with influenza vaccination (e.g. prevented health care visits) outweighing the cost of vaccination. In older adults (aged 50–64 years), several published studies have found that influenza vaccination is likely to be cost-effective, however the results of these studies were often found to be dependent on key assumptions used in the economic evaluations. The uncertainty in influenza cost-effectiveness models can partially be explained by the complexities involved in estimating the disease burden, as well as the seasonal variability in the circulating strains and the match of the vaccine. In healthy working adults (aged 18–49 years), a 2012 review found that vaccination was generally not cost-saving, with the suitability for funding being dependent on the willingness to pay to obtain the associated health benefits. In children, the majority of studies have found that influenza vaccination was cost-effective, however many of the studies included (indirect) productivity gains, which may not be given the same weight in all settings. Several studies have attempted to predict the cost-effectiveness of interventions (including prepandemic vaccination) to help protect against a future pandemic, however estimating the cost-effectiveness has been complicated by uncertainty as to the severity of a potential future pandemic and the efficacy of measures against it.


Research

Influenza research includes molecular virology,
molecular evolution Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genet ...
,
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
, host
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which coul ...
s,
genomics Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
, and
epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evi ...
. These help in developing influenza countermeasures such as
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
s, therapies and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. The Influenza Genome Sequencing Project is creating a library of influenza sequences that will help researchers' understanding of what makes one strain more lethal than another, what genetic determinants most affect
immunogenicity Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...
, and how the virus evolves over time. Solutions to limitations in current vaccine methods are being researched. A different approach uses Internet content to estimate the impact of an influenza vaccination campaign. More specifically, researchers have used data from
Twitter Twitter is an online social media and social networking service owned and operated by American company Twitter, Inc., on which users post and interact with 280-character-long messages known as "tweets". Registered users can post, like, and ...
and Microsoft's Bing search engine, and proposed a statistical framework which, after a series of operations, maps this information to estimates of the influenza-like illness reduction percentage in areas where vaccinations have been performed. The method has been used to quantify the impact of two flu vaccination programmes in England (2013/14 and 2014/15), where school-age children were administered a live attenuated influenza vaccine (LAIV). Notably, the impact estimates were in accordance with estimations from
Public Health England Public Health England (PHE) was an executive agency of the Department of Health and Social Care in England which began operating on 1 April 2013 to protect and improve health and wellbeing and reduce health inequalities. Its formation came as ...
based on traditional syndromic surveillance endpoints.


Rapid response to pandemic flu

The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based) technology and recombinant technologies (proteins and virus-like particles). , more than seventy known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the FDA approved four vaccines against the 2009 H1N1 influenza virus (the 2009 pandemic strain), and expected the initial vaccine lots to be available within the following month. In January 2020, the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) approved Audenz as a vaccine for the H5N1 flu virus. Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine.


Universal flu vaccines

A "universal vaccine" that would not have to be designed and made for each flu season in each hemisphere would stabilize the supply, avoid error in predicting the season's variants, and protect against escape of the circulating strains by mutation. Such a vaccine has been the subject of research for decades. One approach is to use broadly neutralizing antibodies that, unlike the annual seasonal vaccines used over the first decades of the 21st century that provoke the body to generate an immune response, instead provide a component of the immune response itself. The first neutralizing antibodies were identified in 1993, via experimentation. It was found that the flu neutralizing antibodies bound to the stalk of the Hemagglutinin protein. Antibodies that could bind to the head of those proteins were identified. The highly conserved M2 proton channel was proposed as a potential target for broadly neutralizing antibodies. The challenges for researchers are to identify single antibodies that could neutralize many
subtypes In programming language theory, subtyping (also subtype polymorphism or inclusion polymorphism) is a form of type polymorphism in which a subtype is a datatype that is related to another datatype (the supertype) by some notion of substitutabili ...
of the virus, so that they could be useful in any season, and that target conserved domains that are resistant to antigenic drift. Another approach is to take the conserved domains identified from these projects, and to deliver groups of these antigens to provoke an immune response; various approaches with different antigens, presented different ways (as fusion proteins, mounted on virus-like particles, on non-pathogenic viruses, as DNA, and others), are under development. Efforts have also been undertaken to develop universal vaccines that specifically activate a
T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
response, based on clinical data showing that people with a strong, early T-cell response have better outcomes when infected with influenza and because T-cells respond to conserved epitopes. The challenge for developers is that these epitopes are on internal protein domains that are only mildly immunogenic. Along with the rest of the vaccine field, people working on universal vaccines have experimented with vaccine adjuvants to improve the ability of their vaccines to create a sufficiently powerful and enduring immune response.


Oral influenza vaccine

As of 2019, an oral flu vaccine was in
clinical research Clinical research is a branch of healthcare science that determines the safety and effectiveness ( efficacy) of medications, devices, diagnostic products and treatment regimens intended for human use. These may be used for prevention, treat ...
. The oral vaccine candidate is based on an
adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from ...
type5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded RNA hairpin molecule as an
adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesi ...
. In 2020, a PhaseII human trial of the pill form of the vaccine showed that it was well tolerated and provided similar immunity to a licensed injectable vaccine.


COVID-19

An influenza vaccine and a
COVID-19 vaccine A COVID19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID19). Prior to the COVID19 pandemic, an e ...
may be given safely at the same time. Preliminary research indicates that influenza vaccination does not prevent
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quick ...
, but may reduce the incidence and severity of COVID-19 infection.


Criticism

Tom Jefferson, who has led
Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
reviews of flu vaccines, has called clinical evidence concerning flu vaccines "rubbish" and has therefore declared them to be ineffective; he has called for placebo-controlled randomized clinical trials, which most in the field hold as
unethical Ethics or moral philosophy is a branch of philosophy that "involves systematizing, defending, and recommending concepts of right and wrong behavior".''Internet Encyclopedia of Philosophy'' The field of ethics, along with aesthetics, concerns ma ...
. His views on the efficacy of flu vaccines are rejected by medical institutions including the CDC and the
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the lat ...
, and by key figures in the field like
Anthony Fauci Anthony Stephen Fauci (; born December 24, 1940) is an American physician-scientist and immunologist serving as the director of the National Institute of Allergy and Infectious Diseases (NIAID) and the chief medical advisor to the preside ...
. Michael Osterholm, who led the Center for Infectious Disease Research and Policy 2012 review on flu vaccines, recommended getting the vaccine but criticized its promotion, saying, "We have overpromoted and overhyped this vaccine... it does not protect as promoted. It's all a sales job: it's all public relations."


Veterinary use

Veterinary influenza vaccination aims to achieve the following four objectives: # Protection from clinical disease # Protection from infection with virulent virus # Protection from virus excretion # Serological differentiation of infected from vaccinated animals (so-called DIVA principle).


Horses

Horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million yea ...
s with horse flu can run a fever, have a dry hacking cough, have a runny nose, and become depressed and reluctant to eat or drink for several days but usually recover in two to three weeks. "Vaccination schedules generally require a primary course of two doses, 3–6 weeks apart, followed by boosters at 6–12 month intervals. It is generally recognized that in many cases such schedules may not maintain protective levels of antibody and more frequent administration is advised in high-risk situations." It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the
International Federation for Equestrian Sports The International Federation for Equestrian Sports (, FEI) is the international governing body of equestrian sports. The FEI headquarters are in Lausanne, Switzerland. An FEI code of conduct protects the welfare of the horses from physical abu ...
(FEI) requires vaccination every six months.


Poultry

Poultry Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, qu ...
vaccines for bird flu are made inexpensively and are not filtered and purified like human vaccines to remove bits of bacteria or other viruses. They usually contain whole virus, not just
hemagglutinin In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
as in most human flu vaccines. Another difference between human and poultry vaccines is that poultry vaccines are adjuvated with mineral oil, which induces a strong immune reaction but can cause inflammation and abscesses. "Chicken vaccinators who have accidentally jabbed themselves have developed painful swollen fingers or even lost thumbs, doctors said. Effectiveness may also be limited. Chicken vaccines are often only vaguely similar to circulating flu strainssome contain an H5N2 strain isolated in Mexico years ago. 'With a chicken, if you use a vaccine that's only 85percent related, you'll get protection,' Dr. Cardona said. 'In humans, you can get a single point mutation, and a vaccine that's 99.99percent related won't protect you.' And they are weaker han human vaccines 'Chickens are smaller and you only need to protect them for six weeks, because that's how long they live till you eat them,' said Dr. John J. Treanor, a vaccine expert at the University of Rochester. Human seasonal flu vaccines contain about 45 micrograms of antigen, while an experimental A(
H5N1 Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type ...
) vaccine contains 180. Chicken vaccines may contain less than one microgram. 'You have to be careful about extrapolating data from poultry to humans,' warned Dr. David E. Swayne, director of the agriculture department's Southeast Poultry Research Laboratory. 'Birds are more closely related to
dinosaur Dinosaurs are a diverse group of reptiles of the clade Dinosauria. They first appeared during the Triassic period, between 243 and 233.23 million years ago (mya), although the exact origin and timing of the evolution of dinosaurs is t ...
s.'" Researchers, led by Nicholas Savill of the University of Edinburgh in Scotland, used mathematical models to simulate the spread of
H5N1 Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type ...
and concluded that "at least 95percent of birds need to be protected to prevent the virus spreading silently. In practice, it is difficult to protect more than 90percent of a flock; protection levels achieved by a vaccine are usually much lower than this." The Food and Agriculture Organization of the United Nations has issued recommendations on the prevention and control of avian influenza in poultry, including the use of vaccination. A filtered and purified Influenza A vaccine for humans is being developed and many countries have recommended it be stockpiled so if an Avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu.


Pigs

Swine influenza Swine influenza is an infection caused by any of several types of swine influenza viruses. Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) refers to any strain of the influenza family of viruses that is endemic in pigs. As ...
vaccines are extensively used in
pig farming Pig farming or pork farming or hog farming is the raising and breeding of domestic pigs as livestock, and is a branch of animal husbandry. Pigs are farmed principally for food (e.g. pork: bacon, ham, gammon) and skins. Pigs are amenable t ...
in Europe and North America. Most swine flu vaccines include an
H1N1 In virology, influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus. Major outbreaks of H1N1 strains in humans include the Spanish flu, the 1977 Russian flu pandemic and the 2009 swine flu pandemic. It is an orthomyxoviru ...
and an
H3N2 Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predomina ...
strain. Swine influenza has been recognized as a major problem since the outbreak in 1976.
Evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection. Customised (autogenous) vaccines made from the specific viruses isolated, are made and used in the more difficult cases. The vaccine manufacturer
Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-lo ...
claims that the H3N2 strain (first identified in 1998) has brought major losses to pig farmers. Abortion storms are a common sign and sows stop eating for a few days and run a high fever. The mortality rate can be as high as fifteen percent.


Dogs

In 2004,
influenza A virus subtype H3N8 H3N8 is a subtype of the species Influenza A virus that is endemic in birds, horses and dogs. It is the main cause of equine influenza and is also known as equine influenza virus. In 2011, it was reported to have been found in seals. Cats have be ...
was discovered to cause canine influenza. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine was found in 2004.


Annual reformulation

Each year, three strains are chosen for selection in that year's flu vaccination by the WHO Global Influenza Surveillance and Response System. The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. Starting with the 2012–2013 Northern Hemisphere influenza season (coincident with the approval of quadrivalent influenza vaccines), the WHO has also recommended a 2nd B-strain for use in quadrivalent vaccines. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(WHO) coordinates the contents of the vaccine each year to contain the most likely strains of the virus to attack the next year. :"The WHO Global Influenza Surveillance Network was established in 1952 enamed "Global Influenza Surveillance and Response System" in 2011 The network comprises four WHO Collaborating Centres (WHO CCs) and 112 institutions in 83 countries, which are recognized by WHO as WHO National Influenza Centres (NICs). These NICs collect specimens in their country, perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO CCs for high level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year." The Global Influenza Surveillance and Response System's selection of viruses for the vaccine manufacturing process is based on its best estimate of which strains will predominate the next year, amounting in the end to well-informed but fallible guesswork. Formal WHO recommendations were first issued in 1973. Beginning in 1999 there have been two recommendations per year: one for the northern hemisphere and the other for the southern hemisphere. Historical annual reformulations of the influenza vaccine are listed in a separate article. WHO seasonal influenza vaccine composition recommendations:


2020–2021 northern hemisphere

The composition of virus vaccines for use in the 2020–2021 Northern Hemisphere influenza season recommended by the World Health Organization on February 28, 2020, is: for egg-based: * an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus * an A/Hong Kong/2671/2019 (H3N2)-like virus * a B/Washington/02/2019 (B/Victoria lineage)-like virus * a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus for cell- or recombinant-based: * an A/Hawaii/70/2019 (H1N1)pdm09-like virus * an A/Hong Kong/45/2019 (H3N2)-like virus * a B/Washington/02/2019 (B/Victoria lineage)-like virus * a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus The WHO recommends that trivalent vaccines use as their influenza B virus a B/Washington/02/2019 (B/Victoria lineage)-like virus. ;United States The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) recommended that the quadrivalent formulation of egg-based influenza vaccines for the US 2020–2021 influenza season contain the following: * an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus; * an A/HongKong/2671/2019 (H3N2)-like virus; * a B/Washington/02/2019-like virus (B/Victoria lineage); * a B/Phuket/3073/2013-like virus (B/Yamagata lineage). The committee recommended that the quadrivalent formulation of cell- or recombinant-based influenza vaccines for the US 2020–2021 influenza season contain the following: * an A/Hawaii/70/2019 (H1N1)pdm09-like virus; * an A/HongKong/45/2019 (H3N2)-like virus; * a B/Washington/02/2019-like virus (B/Victoria lineage); * a B/Phuket/3073/2013-like virus (B/Yamagata lineage) For trivalent influenza vaccines for use in the US for the 2020–2021 influenza season, depending on the manufacturing method of the vaccine, the committee recommended that the A(H1N1)pdm09, A(H3N2) and B/Victoria lineage viruses recommended above for the quadrivalent vaccines be used. ;European Union The composition of virus vaccines for use in the European Union for the 2020–2021 Northern Hemisphere influenza season recommended by the European Medicines Agency on April 1, 2020, was: Egg-based or live attenuated trivalent vaccines should contain: * an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus; * an A/Hong Kong/2671/2019 (H3N2)-like virus; * a B/Washington/02/2019 (B/Victoria lineage)-like virus. Cell-based trivalent vaccines should contain: * an A/Hawaii/70/2019 (H1N1)pdm09-like virus; * an A/Hong Kong/45/2019 (H3N2)-like virus; * a B/Washington/02/2019 (B/Victoria lineage)-like virus. A B/Phuket/3073/2013-like virus is recommended in addition to the strains mentioned above for the quadrivalent vaccines.


2021 southern hemisphere

The composition of vaccines for use in the 2021 Southern Hemisphere influenza season influenza season recommended by the World Health Organization in September 2020: For egg-based (trivalent): * an A/Victoria/2570/2019 (H1N1)pdm09-like virus; * an A/Hong Kong/2671/2019 (H3N2)-like virus; and * a B/Washington/02/2019 (B/Victoria lineage)-like virus. For cell- or recombinant-based (trivalent): * an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; * an A/Hong Kong/45/2019 (H3N2)-like virus; and * a B/Washington/02/2019 (B/Victoria lineage)-like virus. The quadrivalent version should contain, in addition to the above: * a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus. In Australia, the standard vaccine under the National Immunisation Program for 2021 is the quadrivalent one.


2021–2022 northern hemisphere

The composition of virus vaccines for use in the 2021–2022 Northern Hemisphere influenza season is ;European Union The composition of virus vaccines for use in the European Union for the 2021–2022 Northern Hemisphere influenza season recommended by the European Medicines Agency on March 30, 2021, is: Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Egg-based or live attenuated trivalent vaccines should contain: * an A/Victoria/2570/2019 (H1N1)pdm09-like virus; * an A/Cambodia/e0826360/2020 (H3N2)-like virus; * a B/Washington/02/2019 (B/Victoria lineage)-like virus. Cell-based trivalent vaccines should contain: * an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; * an A/Cambodia/e0826360/2020 (H3N2)-like virus; * a B/Washington/02/2019 (B/Victoria lineage)-like virus. A B/Phuket/3073/2013-like virus is recommended in addition to the strains mentioned above for the quadrivalent vaccines. ;United States The FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the quadrivalent formulation of egg-based influenza vaccines for the US 2021-2022 influenza season contain the following: * an A/Victoria/2570/2019 (H1N1) pdm09-like virus; * an A/Cambodia/e0826360/2020 (H3N2)-like virus; * a B/Washington/02/2019- like virus (B/Victoria lineage); * a B/Phuket/3073/2013-like virus (B/Yamagata lineage). The committee recommended that the quadrivalent formulation of cell- or recombinant based influenza vaccines for the US 2021-2022 influenza season contain the following: * an A/Wisconsin/588/2019 (H1N1) pdm09-like virus; * an A/Cambodia/e0826360/2020 (H3N2)-like virus; * a B/Washington/02/2019- like virus (B/Victoria lineage); * a B/Phuket/3073/2013-like virus (B/Yamagata lineage). For trivalent influenza vaccines for use in the US for the 2021-2022 influenza season, depending on the manufacturing method of the vaccine, the committee recommended that the A(H1N1) pdm09, A(H3N2) and B/Washington/02/2019-like virus (B/Victoria lineage) viruses recommended above for the quadrivalent vaccines be used.


2022 southern hemisphere

The composition of vaccines for use in the 2022 Southern Hemisphere influenza season influenza season recommended by the World Health Organization in September 2021: Egg-based vaccines: * A/Victoria/2570/2019 (H1N1)pdm09-like virus; * A/Darwin/9/2021 (H3N2)-like virus; * B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and * B/Phuket/3073/2013 (B/Yamagata lineage)-like virus. Cell- or recombinant-based vaccines: * A/Wisconsin/588/2019 (H1N1)pdm09-like virus; * A/Darwin/6/2021 (H3N2)-like virus; * B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and * B/Phuket/3073/2013 (B/Yamagata lineage)-like virus. It is recommended that trivalent influenza vaccines for use in the 2022 southern hemisphere influenza season contain the following: Egg-based vaccines: * A/Victoria/2570/2019 (H1N1)pdm09-like virus; * A/Darwin/9/2021 (H3N2)-like virus; and * B/Austria/1359417/2021 (B/Victoria lineage)-like virus. Cell- or Recombinant-based vaccines: * A/Wisconsin/588/2019 (H1N1)pdm09-like virus; * A/Darwin/6/2021 (H3N2)-like virus; and * B/Austria/1359417/2021 (B/Victoria lineage)-like virus


2022–2023 northern hemisphere

The composition of virus vaccines for use in the 2022–2023 Northern Hemisphere influenza season is ;European Union The composition of virus vaccines for use in the European Union for the 2022–2023 Northern Hemisphere influenza season recommended by the European Medicines Agency on March 29, 2022, is: Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Quadrivalent egg-based or live attenuated vaccines should contain: * an A/Victoria/2570/2019 (H1N1)pdm09-like virus; * an A/Darwin/9/2021 (H3N2)-like virus; * a B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and * a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus. Quadrivalent cell-culture or recombinant-based vaccines should contain: * an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; * an A/Darwin/6/2021 (H3N2)-like virus; * a B/Austria/1359417/2021 (B/Victoria lineage)-like virus; and * a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus. ;United States The FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the quadrivalent formulation of egg-based influenza vaccines for the U.S. 2022-2023 influenza season contain the following: * an A/Victoria/2570/2019 (H1N1)pdm09-like virus; * an A/Darwin/9/2021 (H3N2)-like virus; * a B/Austria/1359417/2021-like virus (B/Victoria lineage); and * a B/Phuket/3073/2013-like virus (B/Yamagata lineage). The committee recommended that the quadrivalent formulation of cell- or recombinant-based influenza vaccines for the US 2022–2023 influenza season contain the following: * an A/Wisconsin/588/2019 (H1N1)pdm09-like virus; * an A/Darwin/6/2021 (H3N2)-like virus; * a B/Austria/1359417/2021-like virus (B/Victoria lineage); and * a B/Phuket/3073/2013-like virus (B/Yamagata lineage). For trivalent influenza vaccines for use in the US for the 2022–2023 influenza season, depending on the manufacturing method of the vaccine, the committee recommended that the A(H1N1)pdm09, A(H3N2) and B/Austria/1359417/2021-like virus (B/Victoria lineage) viruses recommended above for the quadrivalent vaccines be used.


Notes


See also

* H5N1 vaccine * Seasonal influenza vaccine brands * Universal influenza vaccine


References


Further reading

* * * * * * *


External links


Inactivated Influenza Vaccine Information Statement
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Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
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Live, Intranasal Influenza Vaccine Information Statement
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Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
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Seasonal Influenza (Flu) Vaccination and Preventable Disease
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Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
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Misconceptions about Seasonal Flu and Flu Vaccines
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Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
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