Is more simply better? Why Pfizer thinks a booster of its Covid vaccine might work against new variants

Could the solution to emerging variants of the coronavirus that causes Covid-19, some of which seem to make current vaccines less effective, be more of the current vaccines?

While Moderna and Pfizer, along with its partner BioNTech, have announced plans to test vaccines specifically targeted at variants of the SARS-CoV-2 virus, they are also planning to test the idea of simply giving people three doses instead of two of their vaccines that have already been authorized. Experts say it’s at least conceivable it could work. 

“It’s certainly reasonable,” said Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. If variants were “completely resistant … you would have to have a second-generation vaccine including the new variant. But if they’re not completely resistant you can give another booster dose with one of these mRNA vaccines and you could get higher titer.”

Creating a higher titer, or antibody level, is like flooding a battlefield with soldiers in the face of a fierce enemy. Eventually, the greater numbers will triumph. That, at least, is the hope.

“It’s somewhat the theory of more is better,” said Ed Walsh, a professor of medicine at the University of Rochester who is running a new Pfizer trial testing three doses. “In many instances, with antibodies, that’s true.”

In an interview, Mikael Dolsten, Pfizer’s chief scientific officer, said that the company believes that its vaccine is still effective against current variants, but that it wants to explore both adding a booster of the already available vaccine and testing whether adding a booster with a new version of the vaccine, which, like Moderna’s, would be designed specifically to target the B.1.351 variant of the virus, which seems most likely to reduce the effectiveness of the vaccines.

Both would be tested first in volunteers who had received the Pfizer/BioNTech vaccine early last year at the beginning of its testing to monitor both any side effects they experience and their antibody levels. 

Dolsten said that Pfizer had confidence in the approach in part because of emerging data in people who had become infected in the spring of 2020 and who then received a dose of the vaccine. “They actually respond vigorously with very strong immune responses to our vaccine,” Dolsten said. “So that gives us at least the scientific rationale.”

Dolsten also said that Pfizer and BioNTech have submitted to the Food and Drug Administration information about a new vaccine construct that would be targeted at B.1.351, and that discussions around studies of such a construct were in their final stages.

One big question for the studies will be the side effects of the new regimen. The second dose of the mRNA vaccines developed by both Pfizer/BioNTech and Moderna can cause fevers, aches, and other temporary reactions as the immune system responds to the vaccine. Will these effects be similar with a third dose? Or will they be about the same, or even less prevalent?

One advantage to working with mRNA vaccines, Walsh said, is that the boost will likely create new antibodies. With the so-called viral vectors, or modified cold viruses, used by Johsnon & Johnson and AstraZeneca, people might develop immunity to the vector itself. Those worries, though, are theoretical. “Immunity to the vector may or may not be a big deal, but it could be,” Walsh said.

Giving booster shots of vaccines also means that manufacturers need to make more, which seems like a big deal when supplies are short both in the U.S. and globally. But Dolsten said that for the U.S., the rollout of boosters, be they additional doses or new versions of the variant, would come after the delivery of 200 million doses of the vaccine expected after July.

In the future, he said, there might be a need for an annual or semi-annual Covid-19 shot, either of the same vaccine or one targeting a new variant.

“I’m still not convinced that we will need to do this every year, because I think there are significant differences to influenza, but at this stage, I’d be very surprised if you weren’t re-dosing at least every three years,” said Geoffrey Porges, an analyst at the investment bank SVB Leerink, on the sidelines of that firm’s SVB Leerink Global Health Conference earlier this week.

Dolsten said that Pfizer sees a role for booster doses, and for avoiding short-term approaches to stretch supply like delaying the second dose, because it will be less effective 

“I think we shouldn’t just look upon what is good for the next two weeks,” Dolsten said. “ We need to slow down the appearance of mutations. So that’s why it’s so important to vaccinate everyone.” But he argued that society should not be satisfied with vaccines that have “mid-tier” activity in doing so.

But a move to a need for booster shots raises another thorny issue: People in the U.S. who want them might end up receiving three shots of vaccines before those in other countries have received one. The vast majority of the world’s countries — 130 of them — have not received any vaccine.

“There are huge inequities here,” said Offit. “The richer countries are the ones getting vaccinated. It’s unfair.”