Bring on the boosters: Studies show Pfizer, Moderna COVID-19 vaccines are less potent against aggressive variant

In early January, researchers from the University of Texas and Pfizer published a preprint study suggesting that Pfizer’s COVID-19 vaccine could protect against a mutation discovered in the U.K. and South Africa. Two weeks later, though, news emerged that Pfizer and its partner BioNTech were working on booster shots to protect against new variants.

Now there’s more evidence that Pfizer’s vaccine—as well as the other authorized mRNA vaccine from Moderna—will need to be updated to fend off aggressive new variants of COVID-19. The data are raising concerns among some analysts of "breakthrough" cases of COVID-19, even in vaccinated people, and the potential for more lockdowns this summer.

In a letter published in The New England Journal of Medicine Wednesday, Pfizer and the University of Texas said a lab study showed the vaccine was about two-thirds less potent against the South African variant of COVID-19 than it was against the original virus.

Moderna also published a letter about its vaccine in NEJM, explaining that its scientists tested its COVID vaccine against several variants, including those found in the U.K., South Africa and Denmark. They found a sixfold decrease in neutralizing antibodies when they tested the vaccine against “the full panel of mutations,” they reported.

Decreased potency doesn't necessarily mean the vaccines are less protective; lab tests don't fully reflect how the shots perform in the real world. One missing piece of information is T-cell activity, which might persist despite mutations, the analysts said. Just how protective they are against the variants remains unknown at this point.

Both companies used serum samples taken from participants in their original vaccine trials to perform the studies. That presented some limitations, they said in their letters, making it impossible to say for certain just how effective the vaccines will be if the new variants take over and start spreading widely. Still, the studies were enough to raise concerns among Wall Street analysts.  

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Analysts at SVB Leerink took a look at the NEJM data from Pfizer and made a sobering prediction: They “expect significant numbers of breakthrough cases of COVID to emerge in vaccinated individuals exposed to the B1.351 variant,” the emerging strain identified in South Africa.

Pfizer has committed to update its vaccine and is engaged in conversations with regulators to determine the next steps, the analysts noted. “We believe that this new version will definitely be required and presume that Pfizer is not declaring as much simply to avoid undermining confidence and uptake for their first-generation product,” SVB Leerink analysts wrote in a note to investors today.

Analysts have voiced concerns about Pfizer’s and Moderna’s responses to the evolution of the coronavirus ever since the new variants started emerging and showing signs of being more infectious than the original pathogen. After Pfizer initially suggested its vaccine offered only slightly weaker protection against the South African variant, for example, Evercore ISI analyst Umer Raffat dashed off a note to investors warning that the company’s analysis didn’t actually include all of the mutations found in that variant.

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Vaccine makers are using lab tests that may not fully reflect how the vaccines will protect against emerging variants in the real world, SVB Leerink analysts wrote. Typically they test antibodies from people who have been vaccinated against engineered “pseudoviruses,” which may paint an incomplete picture of the immune protection the vaccines provide.

SVB Leerink said in today’s note that one missing piece of the puzzle is the protection from the immune system’s T cells, which isn’t reflected in antibody-focused testing. It’s possible, the analysts said, that “the specific reactive T cells for the virus are largely preserved even in the presence of these mutations, thus offering some reassurance that immunity will be more persistent.”

In a note to investors Wednesday, SVB Leerink riffed on the recent news that the COVID vaccine from AstraZeneca and Oxford University, which has not yet been cleared for use in the U.S., also appears to be less potent against the South Africa variant. They predicted that by summer, the new variants will have taken over, and that neither vaccination nor prior infection would offer much protection for anyone. That could bring more lockdowns this summer, they figure.

“As a result, we expect many cities, regions and countries to have to resort to another round of lockdowns and mandatory social distancing, at least until ‘second generation’ vaccines are available, covering the novel … variants,” they said.