The success of one experimental medicine doesn't always mean the same for its trailing rivals. But a better-than-expected result for Pfizer and BioNTech's coronavirus vaccine should boost confidence that other shots behind it are on the right track.
All of the leading coronavirus vaccine developers have made the same bet, targeting a spiky protein on the surface of SARS-CoV-2 that's seen as critical to the virus' ability to latch onto and invade healthy cells.
Past experience with SARS and MERS, along with testing in animals and early clinical studies, had made researchers pretty sure their bet was sound. They have much more surety now, after Pfizer and BioNTech announced an early look at their principal clinical study found their vaccine was more than 90% effective in preventing COVID-19 — powerful evidence that the spike protein is the right target and, plausibly, that other vaccines can work, too
Now, "you're jumping with a net," said Paul Offit, director of the vaccine education center at the Children's Hospital of Philadelphia, said of other vaccines in development.
How well they work will be revealed over the coming weeks and months as vaccine studies from Moderna, AstraZeneca and Johnson & Johnson begin to deliver results. Those results will tell whether Pfizer and BioNTech's early success is an outlier, or if other approaches can also meet the high bar they have set.
Progress of leading coronavirus vaccines
|Developer||Vaccine type||Size of key trial||Status|
|Pfizer, BioNTech||mRNA||44,000 volunteers||Succeeded; FDA application expected soon|
|Moderna||mRNA||30,000 volunteers||Fully enrolled; results expected this month|
|AstraZeneca, Univ. of Oxford||Viral vector||40,000 volunteers||Enrolling; results expected by year end|
|Johnson & Johnson||Viral vector||60,000 volunteers||Enrolling; results expected around year end|
SOURCE: Companies, clinicaltrials.gov
A number of factors will likely come into play, such as how each shot trains the immune system to recognize the spike protein, and what type of response they generate.
Clues from earlier trials are positive for all four of those candidates. The studies compared immune responses in participants who were vaccinated to people who have recovered from COVID-19. In most cases, inoculation led to a result equal or better than what was observed in blood samples of those who had fought off COVID-19.
Pfizer and BioNTech's vaccine, for example, spurred antibody levels in the blood that were nearly three to four times greater than what was seen in samples from recovered patients aged 18 to 55, and up to two times greater than those aged 65 to 85.
Moderna will likely be the next vaccine developer to deliver late-stage trial results, which it expects to have by late November. Like Pfizer and BioNTech, the Cambridge, Massachusetts-based biotech uses messenger RNA, or mRNA, to train the body's immune system against SARS-CoV-2.
The outcome of Moderna's study is expected to be positive, too, particularly after the success of Pfizer and BioNTech's candidate. That will be good news for public health officials looking to roll out mass immunization campaigns, because initial supplies of both will be limited.
But stimulating an antibody response alone may not be sufficient for the vaccines that follow, cautioned Patrick Jackson, an assistant professor of infectious diseases and international health at the University of Virginia.
The modest benefit associated with synthetic antibody drugs like Eli Lilly's newly authorized bamlanivimab, he added, could mean vaccines need to stimulate other parts of the immune system like virus-fighting T cells to successfully prevent disease.
"I think it remains to be seen what the correlate of immunity is going to turn out to be," said Jackson. "It may be more complicated than the antibody [levels]."
Pfizer and BioNTech haven't yet released detailed results, such as antibody and T cell data, from their Phase 3 study.
Jake Becraft, a synthetic biologist who founded the mRNA-focused company Strand Therapeutics, said the encouraging performance of engineered antibodies in COVID-19 patients with high levels of virus — where they may be most effective — isn't necessarily predictive of how vaccine-stimulated natural antibodies neutralize SARS-CoV-2. But comparing the early-stage data from different mRNA vaccines can provide some indication to how well they might prevent disease, he said.
"BioNTech's has at every stage looked better," according to Becraft, who doesn't have ties to either mRNA vaccine developer. "Whereas Moderna just had antibody [activation], BioNTech had T cell priming, which means the T cells in the immune system were activated against the protein, as well as producing antibodies."
In an earlier study, Moderna's candidate led to production of another type of T cell that's thought to be less involved in clearing out viruses.
T cell involvement could end up being important in protection, but only full results from the Phase 3 trials will be able to answer that question conclusively.
Another point of differentiation may be tied to the underlying technology used. mRNA, along with viral vector and DNA-based vaccines, turn on cellular functions that produce the spike protein or a piece of it, and therefore could offer more durable protection than vaccines that simply inject portions of the protein, according to Becraft.
Yet mRNA and viral vector vaccines are less proven than protein-based shots, and aren't given with an immune-boosting adjuvant, potentially limiting their potency.
Nonetheless, the strong effectiveness reported by Pfizer and BioNTech has spurred a belief most of the leading vaccines should work.
"I think [the result] is sending a signal to the ongoing trials that spike really is a target that will transcend different platforms," said Larry Corey, a virologist and co-leader of a National Institutes of Health coronavirus vaccine trials network.