The first interim analysis of the Phase-3 trial of Pfizer’s COVID-19 vaccine (BNT162b2) calls for cautious optimism. The results of the Phase-1 trial, announced in August, showed that the vaccine induced neutralising antibodies and specific T cell (major components of the adaptive immune system) responses in younger and older adults. Neutralising antibodies in younger adults (18-55 years) were 3.8 times more than those in convalescent plasma and 1.6 times more in older adults (65-85 years) in the Phase-1 trial. Neutralising antibodies and T cell responses were also seen in pre-clinical trials on rhesus macaques.
Safe, so far
Though the first interim results of the Phase-3 trial do not provide details, it is likely that neutralising antibodies and T cells responses would have played a vital role in preventing disease in many vaccinated participants — the vaccine showed more than 90% effectiveness in preventing disease. So far, the vaccine appears to be safe as no serious adverse events were reported in the over 43,000 Phase-3 trial participants.
Ninety-four confirmed cases of COVID-19 in trial participants were evaluated in the analysis, but the break-up of how many were among the vaccinated group has not been spelt out. The over 90% effectiveness reported is basically against symptomatic infection. But the nature of infection — mild, moderate or severe — that the vaccine can protect against is not clear.
The efficacy, which was evaluated seven days after the second dose, indicates that protection is achieved 28 days after administration of the first dose, which is again encouraging; the second dose was given 21 days after the first. The endpoint to evaluate vaccine efficacy is when 164 trial participants get infected, irrespective of whether they received the vaccine or a placebo. The company expects that endpoint to be reached by the end of this month. By then, trial participants would have been followed-up for an average of two months — a Food and Drug Administration (FDA)safety requirement for COVID-19 vaccine approval.
While over 90% vaccine effectiveness is much more than what scientists had expected, the effectiveness might change as more cases get reported. In all likelihood, it might drop marginally, but not below the FDA cut off of at least 50% vaccine effectiveness to prevent disease or decrease disease severity. The vaccine will be seen as being truly effective if it has the potential to prevent severe disease and thereby prevent deaths.
The over 90% vaccine effectiveness is based on symptomatic infection. Since not all trial participants have been tested for the virus, it is unclear if the vaccinated participants have been asymptomatically infected. While the inability of the vaccine to prevent asymptomatic infection might not matter for protecting individuals against severe disease outcomes, it might matter in its ability to cut down on transmission.
The duration of protection
The interim results do not reveal how effective the vaccine is in older adults, who are more likely to progress to severe disease and even die. Also, how long the protection lasts after vaccination is not known. It is therefore essential that the trial continues for several more months even when the vaccine is given emergency use authorisation by the FDA. Meanwhile, one way of knowing the duration of protection is by analysing the immune responses of individuals who participated in the Phase-1 trial, which took place a few months ago.
Pfizer is not the only company to use the mRNA platform for COVID-19 vaccine. The COVID-19 vaccine candidate of Moderna and NIAID, which is at an advanced Phase-3 trial, too uses the same mRNA platform; Novavax, Sanofi and GlaxoSmithKline are other vaccine candidates using the same mRNA platform. It is likely that these vaccines too may show similar outcomes. The encouraging results of Pfizer’s vaccine is good news for vaccines that use other platforms, as well. The Oxford University vaccine being tested by AstraZeneca and other vaccines too produced immune responses similar to Pfizer’s in early stage trials and may show encouraging results in Phase-3 trials.