S.S. Vasan is the Honorary Professor of Health Sciences at the University of York and Dangerous Pathogens Team Leader for Australia's science agency CSIRO. In this interview, he talks as a Global Indian Overseas Citizen leading the preclinical response to COVID-19 through the world's first multi-vaccine animal efficacy studies, authoritative analyses on how SARS-CoV-2 is mutating, and what these mean for India in the context of pharmaceutical discovery, manufacturing and health policy.
What is the significance of your world's first multi-vaccine animal efficacy research to the current crisis?
Any vaccine or therapy needs to be evaluated for safety and efficacy in animals (known as preclinical trials), and then humans (called Phase 1, 2 and 3 trials). Sometimes it is not ethical or feasible to do human clinical trials so licensure is based on animal data under the FDA's 'Animal Rule'. During this pandemic we have an unprecedented situation whereby vaccines have entered Phase 1 safety studies in healthy volunteers even before preclinical efficacy studies are completed! Before these candidates can advance to Phase 2, Phase 3, which look at efficacy in humans, we need to complete efficacy studies in animals - so we are on a very tight timescale. There are over 115 COVID-19 vaccine candidates under development, 8 funded by the global Coalition for Epidemic Preparedness 'CEPI', three of which are in Phase 1 clinical trials in humans. The first one is from the US government (Moderna), next is Innovio (DNA vaccine, so far none licensed for human use), and the third is Oxford (established viral vector technology).
We are evaluating the Innovio and the Oxford candidates in our ferret model, having shown for the first time in the world that these animals are susceptible. Oxford′s candidate is currently envisaged by the University as an intramuscular injection, but I′m also evaluating whether giving the vaccine through the nose (intranasally) will result in additional protection through mucosal immunity, and therefore potentially, ′Will one dose be sufficient ′. And with both the Innovio and the Oxford vaccine - I′m looking at whether a single dose would be sufficient or whether you would also require a booster dose. These will have to be repeated in humans of course, based on the findings we and others come up with.
What is the kind of time-scale we are realistically looking at in terms of trials for the programme, and why is this challenging?
In today's world, vaccine development efforts are collaborative and seldom any one person′s endeavour. They generally take 10-15 years from discovery, through development and phased evaluation, to licensure. We are all working at breakneck speed, trying to compress this tenfold to 10-15 months, so it is important to achieve this without compromising on quality, rigour, safety, staff health and wellbeing.
What is the role you see India playing in the field of vaccine manufacturing at scale, given its current pharma and vaccine production base How can we also contribute to pharmaceutical research and development?
Huge. India is a world leader which produces 60 per cent of the world's vaccines. The world's largest vaccine maker, Serum Institute of India, has partnered with Oxford to mass produce the vaccine which is being evaluated in my laboratory (in ferrets) and at the US Rocky Mountain Laboratories (in primates). India is making progress in discovery too. The journal Nature Biotechnology recently profiled 22 vaccine companies including Zydus Cadilla which is reportedly working on an electroporated DNA vaccine (similar to Inovio's candidate that I am evaluating) as well as a live attenuated vaccine. Serum Institute of India is also to manufacture another live attenuated vaccine being developed by Codagenix according to that journal. India's spirit of frugal innovation ('jugaad') is its greatest strength. We need an education system that moves away from rote learning towards problem solving in order to harness creativity. This will help the country to punch above its weight not just in manufacturing but also discovery of drugs and vaccines.
Should we be worried the "D614G” spike mutation will make the virus more contagious and make vaccines obsolete, especially within the context of India′s lockdown easing strategy?
More research is required before we can make any firm conclusions from limited data from this interesting study, which is yet to be peer-reviewed. We analysed the first 181 published sequences of the novel coronavirus and published our findings in the peer-reviewed journal Transboundary and Emerging Diseases.
We did not see this mutation in India or Australia when we published our paper; this pre-print article has also looked at the initial 183 sequences and found that the seven D614G strains were from Brazil, Europe, Mexico and Wuhan, and none from India or Australia. However, after publishing our paper, my CSIRO bioinformatics colleagues have been monitoring whether India and Australia will be affected by this mutation, working in partnership with India's CSIR Institute of Genomics and Integrative Biology.This mutation is now present in roughly two thirds of the global strains that have been sequenced but only represents half of the sequences from India as well as Australia. Should we panic Based on what we know at this point, we do not believe that this poses serious concerns about vaccine development similar to seasonal influenza, where we need to tweak the vaccine each year for Northern and Southern Hemispheres. However, as many vaccines for COVID-19 target the spike region so we will keep a close watch on this and other mutations, as lockdowns are gradually lifted. Note SARS-CoV-2 is an RNA virus with a proof-reading mechanism so it will not mutate as fast as the influenza virus. These viruses exist as a cloud of subtly different variants, so the emergence of strains which replicate efficiently and cause associated pathology is not unexpected. However, susceptible people will also become less common over time, so we will observe selection of strains producing less severe disease but having a prolonged, lower level infection. This is a well-known effect called the 'survival of the flattest'. The environment is a major evolutionary driver in these cases. Some other researchers have observed differences in the titres and growth of virus strains in cell culture, and concluded there are implications for human pathology. There is no direct correlation between the two, so caution is necessary. Unless we have deidentified patient data tied with the many thousands of genome sequences being published, we will be hampered in our efforts to make meaningful deductions at population level
What are some of the biggest learnings for countries around the world, including India, from this pandemic?
Dangerous pathogens don't care about national boundaries. Neither blaming each other, nor whitewashing the root causes of repeated public health emergencies, will help humanity in the long run. Now is our moment to unite and defeat this virus. When we do, we mustn't squander a unique opportunity to rethink and act on how we prevent and prepare for the next big outbreak. It is a matter of when, not if.
We need an education system that moves away from rote learning towards problem solving in order to harness creativity.
Are there particular health policy shifts that will be mandatory in a post-Covid-19 scenario?
Human health and wellbeing can't be achieved in isolation; health of animals and the environment are just as important. If we fail to grasp this 'One Health' approach, if we don't change the way we interact with animals and the environment, we will see more pandemics like Covid-19. There is now a greater awareness in India on matters such as hand washing, personal hygiene and sanitation. If we build this on top of excellent foundations such as 'Swacch Bharat Abhiyan' and 'Ayushman Bharat Yojana' we can help reduce the burden of infectious diseases and free up resources to tackle non-communicable diseases that will become increasingly significant as the population starts to age.