Viral vector vaccine
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A viral vector vaccine is a
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.
that uses a
viral vector Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecu ...
to deliver genetic material ( DNA), which can be transcribed by the recipient's host cells as
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...
coding for a desired
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
(or:
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
) to elicit an immune response. , six viral vector vaccines have been authorized for use in humans in at least one country: four
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 ...
s and two
Ebola vaccine Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had be ...
s.


Technology

Viral vector vaccines use a modified version of one virus as a
vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...
to deliver to a cell a
nucleic acid Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main ...
coding for an
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
for another infectious agent. Viral vector vaccines do not cause infection with either the virus used as the vector, or the source of the antigen. The genetic material it delivers does not integrate into a person's
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
. Viral vector vaccines enable antigen expression within cells and induce a robust
cytotoxic T cell A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular p ...
response, unlike
subunit vaccine A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. A "subunit" vaccine doesn't contain the whole pathogen, unlike live attenuated or inactivated ...
s which only confer
humoral immunity Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it i ...
. Most viral vectors are designed to be incapable of replication because the necessary genes are removed.


Viral vectors


Adenovirus

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 ...
vectors have the advantage of high transduction efficiency,
transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change t ...
expression, and broad viral tropism, and can infect both dividing and non-dividing cells. A disadvantage is that many people have pre-existing immunity to adenoviruses due to previous exposure. Currently,overcoming the effects of adenovirus- specific neutralizing antibodies is being greatly explored by vaccinologists. Such studies include numerous strategies, such as designing alternative Adenovirus serotypes, diversifying routes of immunization and using prime-boost procedures. Human adenovirus
serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the ep ...
5 is often used because it can be easily produced in high
titer Titer (American English) or titre (British English) is a way of expressing concentration. Titer testing employs serial dilution to obtain approximate quantitative information from an analytical procedure that inherently only evaluates as positiv ...
s. As of April 2021, four
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 ...
vector vaccines for
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 ...
have been authorized in at least one country: * The Oxford–AstraZeneca vaccine uses the modified chimpanzee adenovirus
ChAdOx1 ChAdOx1 is an adenoviral vector for vaccines that was developed by the Jenner Institute, University of Oxford. The vector is a chimpanzee adenovirus modified to avoid its replication. Adenoviruses are effective vectors for inducing and boosting ...
*
Sputnik V Sputnik V (russian: Спутник V, the brand name from RDIF) or Gam-COVID-Vac (russian: Гам-КОВИД-Вак, the name under which it is legally registered and produced) is an adenovirus viral vector vaccine for COVID-19 developed by ...
uses human adenovirus serotype 26 for the first shot and serotype 5 for the second. * The Janssen vaccine uses serotype 26. *
Convidecia AD5-nCOV, trade-named Convidecia, is a single-dose viral vector vaccine for COVID-19 developed by CanSino Biologics. It conducted its Phase III trials in Argentina, Chile, Mexico, Pakistan, Russia, and Saudi Arabia with 40,000 participants. I ...
uses serotype 5. Zabdeno, the first dose of the Zabdeno/Mvabea Ebola vaccine, is derived from human adenovirus serotype 26 expressing the
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
of the
Ebola virus ''Zaire ebolavirus'', more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and ot ...
Mayinga variant. Both doses are non-replicating vectors and carry the genetic code of several Ebola virus proteins.


Vesicular stomatitis virus

Vesicular stomatitis virus was introduced as a vaccine vector in the late 1990s.
rVSV-ZEBOV vaccine Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus. When used ...
,known as Ervebo was approved as a prophylactic vaccine for medical use by the FDA IN 2019. The
rVSV-ZEBOV vaccine Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus. When used ...
is an
Ebola vaccine Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had be ...
. It is a recombinant, replication-competent vaccine consisting of
vesicular stomatitis virus ''Indiana vesiculovirus'', formerly ''Vesicular stomatitis Indiana virus'' (VSIV or VSV) is a virus in the family ''Rhabdoviridae''; the well-known ''Rabies lyssavirus'' belongs to the same family. VSIV can infect insects, cattle, horses and pigs ...
(VSV) genetically engineered so that the gene for the natural VSV envelope
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
is replaced with that from the
Kikwit Kikwit is the largest city of Kwilu Province, lying on the Kwilu River in the southwestern part of the Democratic Republic of the Congo. Kikwit is also known in the region under the nickname "The Mother". The population is approximately 458,000 ( ...
1995 Zaire strain
Ebola virus ''Zaire ebolavirus'', more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and ot ...
. It has a unique capability of offering immediate protection following its vaccination and can offer over 90% protection if given post-haste.


Pox virus

Mvabea, the second dose of the Zabdeno/Mvabea Ebola vaccine, is a
modified vaccinia Ankara Modified vaccinia Ankara (MVA) is an attenuated (weakened) strain of the vaccinia virus. It is being used as a vaccine (called MVA-BN, brand names: Imvanex in the EU, Imvamune in Canada, and Jynneos in the US) against smallpox and monkeypox, havi ...
vector, a type of
poxvirus ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated wit ...
. Both doses are non-replicating vectors and carry the genetic code of several Ebola virus proteins. Other viruses that have been investigated as vaccine vectors include
adeno-associated virus Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus ''Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in di ...
,
retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...
(including
lentivirus ''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lent ...
),
cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
,
Sendai virus ''Murine respirovirus'', formerly ''Sendai virus'' (SeV) and previously also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is an Viral envelope, enveloped,150-200 nm in diameter, a negative sense, sing ...
, and avulavirus, as well as
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'', ...
and
measles virus ''Measles morbillivirus'' (MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus ''Morbillivirus'' within the family ''Paramyxoviridae''. It is the cause of measles. Human ...
.


History

Since the development of vaccinia virus as a vaccine vector in 1984, the incorporation of many viruses in vaccination strategies has been studied. Human clinical trials were conducted for viral vector vaccines against several infectious diseases including
Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, whe ...
, influenza viruses,
respiratory syncytial virus Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. ...
,
HIV 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 immune ...
, and
malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
, before the vaccines targeting
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...
, which causes
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 ...
. Two
Ebola vaccine Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had be ...
s using viral vector technology were used in Ebola outbreaks in West Africa (2013–2016) and in the Democratic Republic of the Congo (2018–2020). The
rVSV-ZEBOV vaccine Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus. When used ...
was approved for medical use in the European Union in November 2019, Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. and in the United States in December 2019. Zabdeno/Mvabea was approved for medical use in the European Union in July 2020.


Routes of Administration

The commonly used route for vaccine administration is through
intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...
. The introduction of alternate routes for immunization of viral vector vaccines can induce
mucosal immunology Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled a ...
at site of administration thereby limiting respiratory or gastrointestinal infections. Also studies are being made on how these diverse routes can be used to overcome the effects of specific neutralizing antibodies limiting the use of these vaccines. These routes include
intranasal Nasal administration, popularly known as snorting, is a route of administration in which drugs are insufflated through the nose. It can be a form of either topical administration or systemic administration, as the drugs thus locally delivered ...
, oral,
intradermal Intradermal injection, often abbreviated ID, is a shallow or superficial injection of a substance into the dermis, which is located between the epidermis and the hypodermis. For certain substances, administration via an ID route can result in a ...
and aerosol vaccination


References


Further reading

* {{Portal bar, Medicine , Viruses Virotherapy