Cell-based vaccines are developed from mammalian or more rarely avian or insect

cell line An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cell ...

s rather than the more common method which uses the cells in embryonic chicken eggs to develop the antigens. The potential use of

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 te ...

techniques in developing viral vaccines has been widely investigated in the 2000s as a complementary and alternative platform to the current egg-based strategies. Vaccines work to prepare an immune system to fight off disease by generating an immune response to disease-causing agents. This immune response enables the immune system to act more quickly and effectively when exposed to that antigen again, and is the most effective tool to date to prevent the spread of infectious diseases.

Production

To produce viral vaccines, candidate vaccine viruses are grown in

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

ian, avian or insect tissue culture of cells with a finite lifespan. These cells are typically Madin-Darby Canine Kidney cells, but others are also used including monkey cell lines pMK and Vero and human cell lines HEK 293, MRC 5, Per.C6, PMK, and

WI-38 WI-38 is a diploid human cell line composed of fibroblasts derived from lung tissue of a 3-month-gestation female fetus. The fetus came from the elective abortion of a Swedish woman in 1963. She was disinterested in the fate of the fetus and its s ...

. The candidate vaccine virus strain will replicate using the mammalian cells. Next, the virus is extracted from the cells in the liquid culture, purified, then tested or modified for the specific vaccine being produced.

Advantages

The main benefit of cell-based vaccines is the ability to rapidly produce vaccine supplies during an impending

pandemic A pandemic () is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic (epidemiology), endemic disease wi ...

. Cell-based antigen production offer a faster and more stable production of vaccines compared to embryonic chicken eggs, which produce 1-2 vaccine doses per chicken egg. Though host cells replicate well in chicken eggs, vaccine production with mammalian cells would not rely on an adequate supply of chicken eggs to produce each vaccine. In addition, cell-based vaccines may allow for multiple viral vaccines be produced in the same production platforms and facilities in a more sterile environment. In addition, some strains do not grow well on embryonic chicken eggs. Cell lines grown in synthetic media avoid animal serum, which may pose a sterility problem, more specifically, preventing the spread of transmissible spongiform encephalopathies. Another benefit is the avoidance of egg-allergen. Lastly, cell-based vaccines may be more effective given that, with egg-based vaccines, there is a risk that the virus may mutate (antigenic drift) during its long growth phase in the chicken egg, thus causing the immune system to produce a different antibody than originally intended.

Approved examples

Influenza

Flublok

In 2013, FluBlok, which is produced with insect cells, was approved by the United States Food and Drug Administration, for use in the United States. Developed by Protein Sciences Corporation, it is suitable for people with egg allergies.

Flucelvax

In 2012, the US FDA approved Flucelvax as the first mammalian cell-based

Influenza vaccine Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fr ...

in the United States. The vaccine was produced by Novartis through culturing of the Madin-Darby canine kidney cell line. Specifically, Flucelvax targets four Influenza sub-types which includes Influenza A subtype H1N1, Influenza A subtype H3N2, and two Influenza B viruses. The vaccine is approved for people over the age of three years. As of 2013, Flucelvax had shown similar levels of vaccine efficacy and immunogenicity as traditional egg-based vaccines.

Optaflu

Optaflu Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fr ...

, produced by Novartis, was approved by 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 Euro ...

in 2009, for use in countries affiliated with the European Union. Optaflu is nearly identical to Flucelvax; it is also produced in Madin-Darby canine kidney cells and targets the same Influenza subtypes. The main differences are in release specifications for measuring vaccine lots' safety, efficacy, and quality, mostly due to differences between U.S. and European regulatory standards and tests.

Rotavirus

The Food and Drug Administration approved two mammalian

vero cell Vero cells are a lineage of cells used in cell cultures. The 'Vero' lineage was isolated from kidney epithelial cells extracted from an African green monkey (''Chlorocebus'' sp.; formerly called ''Cercopithecus aethiops'', this group of monkeys ha ...

based vaccines for rotavirus, Rotarix by

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...

and RotaTeq by Merck.

Measles

Attenuvax is a vaccine approved in 2007, against measles developed using a primary cell line.

Smallpox

ACAM2000 ACAM2000 is a smallpox vaccine manufactured by Sanofi Pasteur Biologics Co. The vaccine provides protection against smallpox for people determined to be at high risk for smallpox infection. Background Smallpox is considered a biological threa ...

is a smallpox vaccine approved by the Food and Drug Administration in 2007.

Polio

IPOL, developed by Sanofi Pasteur, was approved by the Food and Drug Administration in 1987.

Rabies

Verorab, developed by Sanofi Pasteur, is a mammalian

based rabies vaccine approved by the World Health Organization.

Others

Ixiaro by Valneva SE for Japanese encephalitis.

References

External links

WHO Vaccine preventable diseases and immunization

Cellosaurus list of cell lines that are/can be used for vaccine production
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