With input from Dr Monica Vasudev

1468: Viral Vector Vaccines Dont Seem to Alter DNA

1. Adenoviral vector vaccines have been in development for decades. However, only a few of them have been approved for use in humans.
2. Adenoviruses are common cold viruses known to cause illnesses that range from cold-like symptoms to bronchitis, gastroenteritis, and conjunctivitis.
3. Most serotypes of adenovirus cause mild illness, while serotype 7 is linked with more severe illness. Older adults and immunocompromised individuals or those having pre-existing respiratory or cardiac disease may have worse illness.
4. Since adenoviruses are so common, one problem with using them in vaccines is that people may already have antibodies against them, which might overwhelm them before they can do their work.
5. Researchers try to overcome this issue by using adenoviruses that humans are not likely to have encountered before.
6. Five adenovirus vector vaccines for COVID-19 are in use across the globe.
7. Each of them works on the same basic principle, while delivery platforms may differ. The AstraZeneca/Oxford vaccine uses the ChAdOx1 platform, which is based on a modified chimpanzee adenovirus.
8. The Johnson & Johnson vaccine makes use of a proprietary AdVac platform, which constitutes a recombinant human adenovirus (adv26). Its the same platform that the company uses in its Ebola virus vaccine (approved in Europe) and its investigational Zika, RSV, and HIV vaccines.
9. Sputnik V uses recombinant human adenoviruses Ad26 and Ad5 for the first and second doses, respectively.
10. Chinas CanSino vaccine uses recombinant human adenovirus Ad5.
11. In the 1990s, study on adenoviruses for use in gene transfer therapy to treat diseases like cystic fibrosis began.
12. Adenoviruses induced robust T and B cell immune responses, leading to quick viral clearance but this limited their purpose in gene therapy. But as adenoviral vectors induced a strong immune response, it made them key candidates for developing vaccines against infectious diseases.
13. Scientists have therefore been working on adenoviral vector vaccines against several viruses, including Zika, RSV, HIV, influenza, dengue, and MERS. During the Ebola outbreaks in West Africa and the Democratic Republic of the Congo, two adenoviral vector vaccines were developed and deployed. Adenoviruses can also be genetically modified for targeting and eliminating cancer cells.
14. The platform that is being used in the AstraZeneca/Oxford vaccine had been in clinical trials in humans for over a decade for several other diseases.
15. Adenoviruses can be used almost like a plug-and-play system. The platform doesnt need to be changed but we may switch out the gene of interest for a particular disease.
16. Earlier work has provided data on dosage and safety of adenoviral vector vaccines in humans.
17. Safety data from several trials in humans showed that they are safe and incite good immune responses.
18. Adenoviral vector vaccines seem to have similar side effects as other types of vaccines like flu shots, such as pain at the injection site, headache, or mild fever.
19. Adenoviruses deliver DNA that enters the cell nucleus.
20. Unlike retroviruses such as HIV or lentiviruses, wild-type adenoviruses do not have the enzymatic machinery which is required for integration into the host cells DNA. This makes them good vaccine platforms for infectious diseases.
21. Engineered adenoviruses used in vaccines have been further debilitated by deleting chunks of their genome. Therefore, they are not able to replicate, further increasing their safety.
22. The cell lines that are used for adenovirus vaccines are well characterized cell lines. They are nonintegrating, which means that there is no evidence in humans and multiple animal models of vector-borne DNA integrating into a host.

(Medpage Today)

 Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA