Biophysicist Raghavan Varadarajan, a professor at the Indian Institute of Science and co-founder of Mynvax, a startup that is working on a SARS-CoV-2 vaccine candidate, spoke to V Shoba on the clinical trial results of the Oxford/AstraZeneca vaccine.
Is it too early to cheer for the Oxford vaccine candidate? What are the caveats to success?
One will have to await the results of Phase 3 trials to know about efficacy. The caveats are:
a) While neutralising antibodies have been induced, as expected from the early animal data, their titers are quite low. A lot of different neutralisation assays are presented in the Lancet paper. However, the format that can be directly compared with other published data is for the VN Marburg assay. Those titers are quite low (see Figure 4A, 4B) and Table S5 in the Appendix) and much lower than those generated by other vaccines for which Phase 1 data are available, for example from Moderna or BioNTech as well as pre-clinical data from several other vaccine candidates including a subunit based vaccine from Novavax.
b) There is little information about the duration of the responses.
mRNA vaccines have never received regulatory approval. Viral vector vaccines have only been approved for use in humans against Ebola. Is the world finally ready to use these experimental vaccines to counter the coronavirus? Are we at a turning point in vaccine development?
This will depend on efficacy in Phase 3 trials, manufacturability, cold-chain requirements etc. Oxford uses a viral vector to express the spike protein whereas Moderna uses an mRNA formulation.
What stage of development is the Mynvax vaccine at?
Pre-clinical studies have yielded promising small animal immunogenicity data.
What risks do fast-track vaccine development and trials carry?
The tools to monitor vaccine efficacy and safety are in place. As long as they are properly applied and monitored, most safety issues can be adequately probed unless there are unexpected issues that crop up many months after immunisation. This is quite unlikely. One of the main issues with vaccine efficacy is duration of protection. This aspect cannot really be fast-tracked and will likely need extensive post-marketing follow up.
Realistically, how long do you think India must wait for a vaccine to hit the market?
I would imagine sometime in the second quarter of 2021 would be reasonable.
Do you think vaccine candidates should undergo human challenge tests?
As far as I know, a human challenge model has not been established. If a safe human challenge model were found, certainly this would be advantageous and could probably be used to compare different vaccine candidates, but it would not be a substitute for a Phase 3 trial. Phase 3 is absolutely necessary. At this point, we don’t know the serum correlates of protection.
What implications do the mutations in the genome of the coronavirus have on vaccine development? The flu vaccine is modified every year to keep up with the latest strains in circulation.
At the present time, viral mutations do not seem to be a significant issue to worry about for a vaccine. Mutation rate is slower than for influenza and in any case in a naïve population, there is probably lower immune selection pressure for mutations to arise.
Has the novel coronavirus been found to develop resistance to any antivirals so far?
The current small molecules used in the clinic are not really specific antivirals, so I don’t believe mutations are a worry at the moment.