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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.”

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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.”

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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.”

  • Part of the problem with distributing the current vaccines to other less developed countries is the special ultra-cold storage/shipping and critical handling temperatures required by both the Pfizer and Moderna vaccines. With the Johnson and Johnson vaccine now just approved, which only needs normal refrigeration, and several others like it almost through their testing phase, wider distribution becomes much more logistically feasible.

  • Once again I am very grateful to Stat for an article which actually explained something. The mainstream media has been referring to vaccines designed specifically for the variants as “boosters” and it was driving me crazy because that is not what I think of as a “booster” a “booster” is just another shot of the same vaccine.
    Way back in Intro to Microbiology they told us antibodies were highly specific- that makes me question the idea of just giving more -but what makes me yet more skeptical – we were also told a lot of different types of antibodies are generated by an actual infection – antibodies to almost any part of the pathogen which is exposed- and yet, the variants are making a LOT of people who were sick less than a year ago, sick again, now, in Manaus and South Africa. Are the vaccines going to generate more affective immune response than actual infection and recovery ? That seems awful unlikely.

  • If the US subsidized, and had the research and development of the vaccine done by American scientists in the US itself, it does not seem selfish to take care of American citizens first and then share the vaccine with other countries.

    • In the case of Pfizer, they were not part of Operation Warp Speed and took no federal money. Moreover, their partner who helped develop the vaccine is BioNTech, a German company. It’s not that simple.

    • The problem with national vaccination is very simple: If you vaccinate first only in US, then you will give time to the virus to mutate further in other parts of the world, lets say in the less-developed countries. If or when a new mutation appears to avoid the vaccine efficiacy in a less developed country, then your usa vaccinated people will have an issue with the new mutation. No matter where you live in the world, we humans are all together in this, so vaccination can go as fast as possible everywhere in the same time.

    • Guestty – I am not against helping the rest of the world by the gift of vaccines – but from a purely selfish standpoint, the thing to do is get the vaccine to everyone here, while shutting the door on international travel – have a two week quarantine enforced by cops, armed cops guarding the hotel rooms travelers would be compelled to stay in.
      This of course does not solve the problem of variants arising in the 95% of the world – perhaps, 99.9% – (I do not think we can rule out variants arising among wild animals, bats, weasels, primates, etc, and we have less than 5% of those creatures)

      But if you shut the door, tight, which Trump and CDC failed to do before the “variants of concern” arrived here- but if you shut it now, and give all the vaccines we can get to US residents – and make new vaccines for what we have here now – that is by far the best way to protect those in the US, not trying to vaccinate 19 times the number of people in the US to stop further mutation.

  • Over seven billion people live on this planet. It’s unrealistic to assume or believe that any Covid vaccine can be equitably distributed to everyone. A one-stop vaccine like Johnson & Johnson’s is the best solution to this problem. I received my second Moderna shot last month. This disease will be with us for the foreseeable future. I expect more booster shots to come.

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