May 20, 2020

expert reaction to two studies looking at immunity against SARS-CoV-2 and evaluating a series of DNA vaccine candidates in rhesus macaques

Two studies, published in Science, have looked at immunity against SARS-CoV-2 in rhesus macaques conferred by a series of DNA vaccine candidates.

Prof Daniel Altmann, Professor of Immunology, Imperial College London, said:

“Dan Barouch and colleagues at Harvard and elsewhere have published two papers in Science that offer well-substantiated answers to some current questions about COVID-19 immunity and vaccination.

“The first paper by Chandrashekar et al attempts to input some detail into basic questions of the pathogenesis of COVID-19 and whether recovery yields immunity to reinfection. To answer this they generate a virus infection model in macaques, which looks rather faithful to the human situation. They show that the pattern of infection reiterates many features of human infection and that many facets of the immune response are induced. They allow recovery for 5 weeks and then re-challenge with fresh virus, finding that there’s virtually complete resistance to disease and few clinical symptoms. This seems a useful and clear answer. Of course the big caveat is that this tells us about immunity at 5 weeks, whereas the answer we really want to know is about immunity at 1 or 2-years, especially considering that natural infection with Coronaviruses is sometimes thought to induce rather transient immunity.

“In the second paper by Yu et al, they immunise groups of macaques with different versions of a DNA vaccine (encoding different antigens from the virus). Again, they find good levels of immunity induced across several different parameters, including neutralising antibody and cellular responses by specific T cells. When macaques are then challenged with live virus, there is substantial protection with great reductions in the viral loads recovered. Would this be enough to give real-life, functional protection from disease in humans? Probably. We need to bear in mind that we’re hunting here for ‘good enough’ protection, not complete ’sterilising immunity’ which might be hard to achieve. There are many things to like about this detailed study: they had no need to add any adjuvants (which raise concerns for some people), there was no induction of ’Th2 immunity’ – sometimes associated with adverse events in respiratory vaccines, and they use machine learning to identify the all-important ‘correlates of protection’, which here turns out to map to the level of virus-neutralising antibody.

“Most importantly, the study is a reminder to all that there are a great many vaccine approaches being tested in several countries, and they are rather diverse in approach, giving different answers about the size of response, number of boosts needed, protectiveness, safety, durability, not to mention, ease of production and supply. Rather than promoting this as a simple race to the finish line, scientists need to remind our policy-makers that the devil is in the detail, and we might be better served by calmly evaluating the strengths and weaknesses of several candidates, opting for the best, not just the first.”

Prof Lawrence Young, Professor of Molecular Oncology, University of Warwick, said:

“These are very encouraging studies which show that a simple DNA vaccine can induce protective immunity against SARS-CoV-2 in macaques and that a previous infection with the virus can also provide protection suggesting that previously infected individuals will be protected from re-infection.

“SARS-CoV-2 infection in macaques will be different from that in humans including the ability of the virus to infect many different cells and tissues in humans. The immune responses will also be very different.

“Low level virus replication was observed in the vaccinated animals and after re-infection indicating that completely eliminating the infection (so-called sterilising immunity) was not achieved.

“The results are very similar to the previous findings of the ChAdOx1 nCoV-19 vaccine in rhesus macaques. However, a DNA vaccine is much easier to manufacture at scale and this is the first indication that a previous infection is protective.

“The study by Chandrashekar et al suggests that previously infected individuals will be protected from re-infection. We will have to wait for the current clinical trials using convalescent plasma (passive immunization) to be sure that antibodies are protective. From what we know about other coronavirus infections, any protective immunity is likely to be effective for a short time – perhaps only up to 2 years post-infection.”

Prof Gordon Dougan, Jeffrey Cheah Biomedical Centre, University of Cambridge, said:

“These look fairly encouraging data on a first look. Main issues are that DNA vaccines do work okay in animals other than humans so it is still a big ask to get this data to translate to a human vaccine.

“On the rechallenge study, this is also encouraging but I note this was at 35 days so the animals would still be in ‘recovery’ from the first challenge and would need a much longer gap to really test immunity.

“The neutralisation data also encouraging but a long way to become a correlate of immunity. Would need much more rigorous evaluation (not in macaques). Authors will understand this of course.”

‘SARS-CoV-2 infection protects against rechallenge in rhesus macaques’ by Chandrashekar et al and ‘DNA vaccine protection against SARS-CoV-2 in rhesus macaques’ by Yu et al were published in Science on Wednesday 20 May.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests:

Prof Danny Altmann: “None”

Prof Lawrence Young: No conflicts of interest

None others received.