News from Covid-19, a candidate for the Modern Inc vaccine, which induces the creation of antibodies against SARS CoV-2 in all trial participants: research into the effects of the Phase 1 clinical trial published in the New England Journal of Medicine shows that the vaccine is also relatively: it provoked a degree of euphoria. Reports in The Guardian have also cited encouraging (albeit unconfirmed) effects of phase one clinical trials of the Oxford University vaccine candidate. In fact, the overall direction of progress in candidate vaccines has been encouraging so far. Still, the global network would do well to liven up their expectations.
It is vital to remain in the brain the sensible words of Merck CEO Kenneth Frazier about the exaggeration (even involuntary) around a successful vaccine, especially one that would be in the short term, being a “very bad service” to the public. Frazier, in an interview with a Harvard Business School professor, said there are many clinical and logistical hurdlees over which a vaccine candidate will have to succeed to succeed. He deserves to know this, having been at the helm of a company that has developed many successful vaccines, adding one of the few approved anti-Ebola. Of course, urgency in this case is inevitable, and with the infrastructure supporting the studies and progression that has evolved in recent years, some facets of the trials are likely to no longer require the time they had before. However, it is also mandatory to perceive that vaccine applicants 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.
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