Viral vector vaccine
A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA), which can be transcribed by the recipient's host cells as mRNA coding for a desired protein (or: antigen) to elicit an immune response. As of April 2021[update], six viral vector vaccines have been authorized for use in humans in at least one country: four COVID-19 vaccines and two Ebola vaccines.
Viral vector vaccines use a modified version of one virus as a vector to deliver to a cell a nucleic acid coding for a antigen 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.
Viral vector vaccines enable antigen expression within cells and induce a robust cytotoxic T cell response, unlike subunit vaccines which only confer humoral immunity. Most viral vectors are designed to be incapable of replication because the necessary genes are removed. In order to be widely accepted and approved for medical use,the development of viral vector require a high biological safety level. Consequently, non or low pathogenic viruses are often selected. In most cases, viruses are genetically engineered to be replication-defective. Despite the fact that replication-deficient viral vectors are generally safer than replication-competent viral vectors, they may require a higher dose or a prime-boost regimen to induce sufficient immunity. Replicating vectors imitates natural infection, which stimulates the release of cytokines and co-stimulatory molecules that produce a strong adjuvant effect. When a replication-deficient viral vector does not elicit the most appropriate responses, the incorporation of an adjuvant may be required to boost the immune response against the encoded antigen. Viral vector-based vaccines require assessment of efficacy and safety, including immunogenicity,genetic stability, ability to evade pre-existing immunity, replication deficiency or attenuation, and genotoxicity Compared to the other vaccine platforms, viral vector vaccines are more stable, requiring less strigent storage and handling conditions. Example is Ad26.COV2.S,an adenoviral based vector vaccine.
The advantages of Viral vector vaccine include high efficiency gene transduction, specific delivery of genes to target cells and ability to induce potent humoral and cellular immune responses. The immunogenicity is further enhanced through intrinsic vector motifs that stimulate the innate immunity pathways,thus, the use of expensive and mostly reactive adjuvants can be omitted.Viral vectors can use the host-cell protein-processing pathways that lead to antigen presentation via major histocompatibility complex class I and consequent cytotoxic T-cell stimulation In addition, viral vectors can be produced in high quantities at relatively low costs, which allows the use of these systems in low-income countries.
The first viral vector created from the SV40 virus by genetic engineering was introduced in 1972. Subsequently, other viruses, including adenoviruses, poxviruses, herpesviruses, vesicular stomatitis virus, cytomegalovirus and lentiviruses, have been designed into vaccine vectors capable of inducing a robust immune responses. Vaccinia virus and adenovirus are the most commonly used viral vectors.
Adenovirus vectors have the advantage of high transduction efficiency, transgene 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.The seroprevalence against Ad5 in the US population is as high as 40%–45%. Most Adenovirus vectors are replication-defective because of the deletion of the E1A and E1B viral gene region. 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 5 is often used because it can be easily produced in high titers.
- The Oxford–AstraZeneca vaccine uses the modified chimpanzee adenovirus ChAdOx1
- Sputnik V uses human adenovirus serotype 26 for the first shot and serotype 5 for the second.
- The Janssen vaccine uses serotype 26.
- Convidecia uses serotype 5.
Zabdeno, the first dose of the Zabdeno/Mvabea Ebola vaccine, is derived from human adenovirus serotype 26 expressing the glycoprotein of the Ebola virus 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, known as Ervebo was approved as a prophylactic vaccine for medical use by the FDA IN 2019. The rVSV-ZEBOV vaccine is an Ebola vaccine. It is a recombinant, replication-competent vaccine consisting of vesicular stomatitis virus (VSV) genetically engineered so that the gene for the natural VSV envelope glycoprotein is replaced with that from the Kikwit 1995 Zaire strain Ebola virus. In most VSV vaccine vectors,attenuation provides safety against its virulence.
Vaccinia virus, which is a member of pox virus family, is a large, complex and enveloped virus. Due to its large size, the viral genome capacity for foreign gene insertion is high. Modified vaccinia Ankara (MVA) is a highly attenuated strain derived from the vaccinia strain Ankara. Mvabea, the second dose of the Zabdeno/Mvabea Ebola vaccine, is a modified vaccinia Ankara vector, a type of poxvirus. 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, retrovirus (including lentivirus), cytomegalovirus, Sendai virus, and avulavirus, as well as influenza virus and measles virus.
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, influenza viruses, respiratory syncytial virus, HIV, and malaria, before the vaccines targeting SARS-CoV-2, which causes COVID-19.
Two Ebola vaccines 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 was approved for medical use in the European Union in November 2019, 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. The introduction of alternate routes for immunization of viral vector vaccines can induce mucosal immunology 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, oral, intradermal and aerosol vaccination
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