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Credit: Eva Marie Uzcategui / Bloomberg via Getty
Works! Scientists have received with cautious optimism a press release declaring positive interim results from a coronavirus vaccine trial, the first to report the final round of ‘phase III’ human testing.
Pharmaceutical Pfizer’s announcement on Nov.9 offers the first compelling evidence that a vaccine can prevent COVID-19, and bodes well for other COVID-19 vaccines in development. But the information released at this early stage does not answer key questions that will determine whether the Pfizer vaccine, and others like it, can prevent the most severe cases or quell the coronavirus pandemic.
“We need to see the data at the end, but that still doesn’t dampen my enthusiasm. This is fantastic, ”says Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai in New York City, who is also one of more than 40,000 participants in the trial. “I hope I’m not in the placebo group.”
The vaccine, which is being jointly developed by BioNtech in Mainz, Germany, consists of molecular instructions, in the form of messenger RNA (mRNA), for human cells to produce the coronavirus spike protein, the key target of the immune system for coronavirus. . The two-dose vaccine showed promise in animal studies and early-stage clinical trials. But the only way to know if the vaccine is working is to give it to large numbers of people and then follow it for weeks or months to see if they become infected and show symptoms of the disease. These results are compared with those of a group of participants who received a placebo.
In the press release, Pfizer and BioNtech said they had identified 94 cases of COVID-19 among 43,538 trial participants. The companies did not indicate how many of those cases were in the placebo group or among those who received the vaccine. But they said the division of cases between the groups suggested the vaccine was more than 90% effective in preventing the disease, when it was measured at least a week after trial participants had received a second dose of vaccine, three weeks later. from the first. The trial will continue until a total of 164 COVID-19 cases are detected, so initial estimates of the effectiveness of the vaccines could change.
Although the vaccine may not be as effective once the trial is complete and all the data has been analyzed, its effectiveness is likely to remain well above 50%, says Eric Topol, a cardiologist and director of the Translational Institute of Scripps Research in La Jolla, California. This is the threshold that the US Food and Drug Administration says it would require for a coronavirus vaccine to be approved for emergency use. “I think this is an extraordinary achievement, even without much detail, because there was no guarantee of the efficacy of the vaccine before getting the first reading of a trial,” says Topol.
Questions remain
What’s missing, Topol and other scientists say, are details about the nature of the infections the vaccine can protect against, whether they are mostly mild cases of COVID-19 or they also include a significant number of moderate and severe cases. “I want to know the spectrum of diseases the vaccine prevents,” says Paul Offit, a vaccine scientist at the University of Pennsylvania who sits on an advisory committee to the US Food and Drug Administration that will evaluate the vaccine next month. “He would like to see at least a handful of cases of severe disease in the placebo group,” he adds, because it would suggest that the vaccine has the potential to prevent such cases.
It is also unclear whether the vaccine can prevent people who show no symptoms of COVID-19 or who show only very mild symptoms from spreading the coronavirus. A vaccine that blocks transmission could hasten the end of the pandemic. But it will be difficult to determine whether the Pfizer vaccine, or others in late-stage trials, can achieve this, Krammer says, because it would involve routine testing of trial participants. “You can’t do that with 45,000 people,” he says.
Another missing detail is how well the vaccine works in different groups of trial participants. “We still don’t know if it works in the population that needs it most, which is the elderly,” says Krammer. Due to the small number of cases that will accumulate before completion, the Pfizer trial is unlikely to conclusively determine the efficacy of the vaccine in subgroups such as those 65 and older or African-Americans, Offit says. But he adds that if the trial included enough participants from those groups, it is possible to generalize the likely effectiveness of vaccines in these groups from their overall efficacy. In the press release, Pfizer and bioNtech reported that 42% of the participants had a “racial and ethnic background.”
Lasting immunity?
A key unanswered question is how long the vaccines will last. Based on when the trial began and previously published data on immune responses in early-stage trials, many trial participants likely still have high levels of protective antibodies in their blood, says Rafi Ahmed, an immunologist at the Emory University in Atlanta, Georgia. “For me, the main question is what happens six months later, or even three months later,” he says.
There will be an opportunity to answer that question if the trial continues for several more months, says Ahmed. The answers could also come from analyzing the immune responses of people who participated in the early-stage trials of the Pfizer vaccine, some of whom may have received the vaccine up to 6 months ago. And while little is known about the long-term effectiveness of the vaccine, this is unlikely to delay its use, says Ahmed. “I don’t think we should say, ‘Well, I’ll just take a vaccine that protects me for five years.’ I mean, that could be crazy. “
The results are a boost for other COVID-19 vaccine developers. That includes a vaccine developed by Moderna, a biotech company from Cambridge, Massachusetts, and the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, that is also made up of mRNA, Krammer says. “I hope Moderna shares go up today.”
Shane Crotty, a vaccine immunologist at the La Jolla Institute for Immunology in California, believes Moderna isn’t the only developer who should celebrate Pfizer’s preliminary results. Several other candidate vaccines elicited immune responses similar to those elicited by Pfizer’s vaccines in early-stage trials, so they should work well too.
One thing about the Pfizer vaccine is certain: Regulators will soon determine if it is ready for implementation. The company said it would seek an emergency use authorization from the FDA around the third week of November, by which time participants will have been followed for an average of 2 months, an FDA safety requirement for COVID vaccines. -19.
And while researchers want to see the data behind the Pfizer vaccine trial, they are prepared to accept the accompanying warnings. “Right now we need a vaccine that works,” Krammer says, even if it works for only a few months or doesn’t stop transmission. “That’s what we need to get back to half normal.”
