Studies from COVID-19 vaccine makers and public health officials have been suggesting for a while that protection provided by the vaccines wanes over time. In a new study published on Sept. 15 to a preprint server—the study is not yet peer-reviewed—researchers at Moderna, which makes one of the two mRNA COVID-19 vaccines (the other is from Pfizer-BioNTech), report that people vaccinated within the last eight months had 36% fewer breakthrough infections than those who were vaccinated a year ago.
That suggests vaccine-induced immunity is likely highest shortly after people get their recommended two doses of the vaccine, and starts to drop afterward. The Moderna vaccine received emergency use authorization (EUA) from the U.S. Food and Drug Administration in Dec. 2020; the FDA is currently reviewing the company’s request for full approval of the shot.
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The latest data are part of an ongoing Phase 3 study of that includes more than 14,000 people who were randomly assigned to receive either two doses of the Moderna vaccine or two doses of placebo from July to October 2020, and more than 11,000 people who were originally assigned to receive placebo doses from December 2020 to March 2021 and, after the EUA was granted, chose to receive two doses of the vaccine. In that latter group, which completed its two-dose regimen about eight months ago, 88 people tested positive for COVID-19, compared to 162 people who had breakthrough cases in the earlier vaccinated group. That means the more recently vaccinated people had a 36% lower incidence of breakthrough infections than those immunized a year ago. (Overall, only 19 of the 250 breakthrough cases were severe.)The results, Moderna says, suggests protection wanes over time, which is why the company submitted data to the FDA to authorize a booster dose to provide better protection against COVID-19.
To make its case for an additional dose, Moderna’s scientists published results from another study on Sept. 15, in the journal Nature Medicine, comparing the efficacy of four different types of booster approaches. In the small study of 79 people, some received a third dose of the same two-dose vaccine they already received, some received a lower dose of this vaccine, some got a dose of a vaccine developed specifically against the Beta variant, and a final group received a combination of the original and Beta variant shots. The data confirmed that about six months after people are fully vaccinated with two doses, levels of antibodies that can neutralize the original version of SARS-CoV-2 dropped by about six- to seven-fold. But boosting with an additional dose of any of the four vaccines the researchers tested increased levels of antibodies about a month later. The combination dose was the most effective, increasing antibody levels by 46-fold, compared to a 16.7-fold increase with a third dose of existing vaccine, an 11.3-fold increase with the Beta-specific booster, and a 9.2-fold increase with the lower dose Beta-specific booster.
More encouraging, the researchers say, is that these antibody levels reached or exceeded—in some cases as high as by 4.4 times—those produced in the first month after two doses of the vaccine—even against variants like Beta, Gamma and Delta. That suggests the immune system retains some memory of SARS-CoV-2 and the booster can amplify and accelerate the immune response to build on the original protection against the virus and even tackle variants that have mutated from the original form.
“We’ve been saying that we are going to have to have a variant booster, and that booster is going to have to be multivalent [and able to recognize different variants],” says Dr. Stephen Hoge, president of Moderna. “Then the clinical trial data came in … and we see a small benefit when we match a variant strain with the booster. But it’s not dramatic, and it’s not overwhelming benefit. In fact the [original] vaccine does really well against Delta.”
The idea is similar to the concept of a rising tide lifting all boats. The Delta variant, fortunately, has not learned to escape the immune system’s defenses; its success spreading among human populations has largely been because of its ability to flood the zone and quickly infect as many cells as possible in any unprotected person. Confronting that onslaught with an equally massive immune response, which, it seems, can be generated by a booster dose of the original vaccine, is sufficient to keep Delta at bay—and keeping any virus that does get through from causing severe disease.
Hoge says he is not worried so much about Delta, as about what might come after Delta. While the Delta variant hasn’t learned to escape the immune system yet, other variants, including Beta and Gamma, have shown signs of such evolution. If, over the course of the next few months, some of the known strains find a way to meld their respective strengths, the resultant variant could become a public health nightmare. Moderna is working on a vaccine that would target Beta, Gamma and Delta, in case such a strain does actually emerge this winter. “The [mRNA] platform allows us to take a chance and get ahead of that possibility and be ready if we need it,” says Hoge. That booster could be ready and tested in a small group of people by the end of the year and available more widely in the first quarter of 2022 if needed, he says.
In the meantime, Moderna has already developed a vaccine designed specifically to protect against the Delta variant, but Hoge says it’s not likely it would be necessary as a booster, since the existing vaccine can generate an adequate enhanced immune response even against Delta.
Researchers at Pfizer-BioNTech, who have also developed an mRNA COVID-19 vaccine, built a Delta-specific vaccine as well, and have begun testing it in the lab. But infectious-disease experts don’t agree on whether a COVID-19 booster is even needed at this point. While both Pfizer and Moderna have submitted data to the FDA as a part of requests to green-light an additional dose of their vaccines, and the White House COVID-19 team backs the idea, experts at the FDA do not seem convinced a booster is necessary. Ahead of a Sept. 17 FDA advisory committee meeting of independent experts who will review the latest data on Pfizer-BioNTech’s booster, the agency recently posted a report expressing the need for strong data to support the need for a booster dose. “Overall, the data indicate currently US-licensed or authorized COVID-19 vaccines still afford protection against severe COVID-19 disease and death in the United States,” the FDA scientists said. “There are many potentially relevant studies, but the FDA has not independently reviewed or verified the underlying data or their conclusions.”