Covid vaccine progress so far is encouraging, but there are still too many uncertainties that need too be resolved.
News of Moderna Inc’s Covid-19 vaccine candidate inducing creation of SARS CoV-2 neutralising antibodies in all trial participants—analysis of Phase 1 clinical trial findings published in the New England Journal of Medicine shows that the vaccine is also relatively safe—has sparked some degree of euphoria. Reports in The Guardian have also talked about encouraging results (though unconfirmed so far) from the phase one clinical trials of the Oxford University’s vaccine candidate. Indeed, the general direction of progress on vaccine candidates has been encouraging so far. Even so, the global community would do well to temper its expectations.
It is important to keep in mind Merck CEO Kenneth Frazier’s sage words on hype (even if unintentional) around a successful vaccine, especially one touted to become available in the near term, being a “great disservice” to the public. Frazier, in an interview with a Harvard Business School professor, stated that there are many scientific and logistical obstacles that a vaccine candidate must overcome to prove successful. He should know, having been at the helm of a company that has developed many successful vaccines, including one of the few approved against Ebola. To be sure, the urgency in the present instance is ineluctable, and with infrastructure supporting R&D having evolved rapidly over the past few years, it is likely that certain aspects of trials now don’t demand the amount of time they did earlier. However, there is also a need to understand that vaccine candidates may face many limitations.
Studies from China, Germany and the UK show that the antibodies Covid-19 patients develop against SARS CoV-2 could be short-lived; indeed, an ongoing ICMR study reports that nearly 25% of the samples of plasma from recovered patients didn’t have any antibodies. Apart from the implications for plasma donations for convalescent plasma therapy, this also could be an indication that developing long-term immunity, whether because of infection or vaccine-induced, could be difficult, even with T-lymphocytes (one part of immune system memory) in play.
If vaccine trials and other research eventually show this, a one-shot-and-done vaccine would be unlikely, too. And, with rapid mutations—66,000 genomic sequences have been reported so far—vaccine development, boosters included, will be a complicated affair. There are other potential limitations also, which need to be studied over a longer time-frame than what all the ‘fast-track vaccine’ talk has focussed on. For instance, even though adenovirus vector vaccines (involving weakened viral vectors that act as a carrier for pathogen genes encoding for the latter’s proteins, which then induce the body to create corresponding antibodies) are believed to have certain advantages over other vaccines—including DNA vaccines on which these are based—experts are watching if it will also mean if such vaccines are less effective.
Neutralising antibodies against human adenoviruses are common—more so in African nations than in Asian or European ones—and there is a need to see how effective vaccines like CanSino Biologics’s candidate and Johnson & Johnson’s candidate fare eventually. Indeed, as some immunologists have opined, even the site of the administration of such vaccines could determine whether antibodies against the vector are activated and render the vaccine ineffective.
Vaccine talk perhaps needs to bring in a balance between optimism and caution. There are too many uncertainties right now to be talking of launch in a matter of months—or, for that matter, even a near-term deadline. There is also a need to fuel research on other pharmacological interventions—such as antiviral molecules, monoclonal antibodies (new research findings that establish the genetic backbone of antibodies that target the virus’s spike protein, the IGHV3-53 gene), new and existing immunomodulatory compounds. The world will do well to echo Anthony Fauci’s “cautious optimism” on vaccines in the meanwhile.