Booster Counteracts Waning Immunity of Initial Pfizer Doses, Data Show

Marcia Frellick

December 01, 2021

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A third (booster) shot of the Pfizer-BioNTech COVID-19 mRNA vaccine appears to counteract the waning protection of the first two shots, at least in the short term, according to new data published online November 30 in JAMA Internal Medicine.

Tal Patalon, MD, with the Kahn Sagol Maccabi Research and Innovation Center, Maccabi Healthcare Services, in Tel Aviv, Israel, led a case-control study of 306,710 Israeli adults aged 40 years and older.

The researchers found that the estimated odds of becoming infected with SARS-CoV-2 were significantly reduced within a few weeks for those who got the booster compared with those who received only two primary shots.

Comparing those groups, there was an estimated odds ratio of 0.14 (95% CI, 0.13 – 0.15) 28 to 65 days following the booster ― an 86% reduction in the odds of testing positive for SARS-CoV-2 after the booster.

"This reduction comes on top of the reduction in the risk conferred by the first 2 doses," the authors write.

"Biologically, this is what we might expect. The magnitude of the effect is impressive," Stuart Ray, MD, professor in the Division of Infectious Diseases of Johns Hopkins Medicine in Baltimore, Maryland, told Medscape Medical News,

He said the study design ― using positive test results as a surrogate of getting infected ― was a reasonable approach.

The question, he said, is how long those effects can be sustained.

Dr Stuart Ray

"We need to see this work replicated, but it makes sense biologically and it aligns well with our prior work with initial dosing," Ray said. "We saw a dramatic reduction in testing positive in the initial trials."

The timing of the third dose is an area of high interest, he said. He noted that with other vaccines, including those for hepatitis B, human papillomavirus, and shingles, doses are adminsitered at different intervals.

"Vaccinating with that kind of resting period really does tend to generate the best responses," Ray said.

"I don't think this study suggests we'll be getting extra doses every few months," he said.

He said over time, data will inform the most effective intervals, "and, of course, in the context of the Omicron variant, whether this kind of protection extends to something as different as Omicron."

Ray said the study by Patalon and colleagues will likely help motivate those who run healthcare systems to consider ramping up efforts to get employees vaccinated with a third dose.

"If they are public facing, they are less likely to pass on infection to those they care for," he said. "It's the kind of data that have motivated us to vaccinate our workforce in healthcare for other transmissible infections."

Israel's Nationwide Campaign

The results from Israel come in the wake of a nationwide booster campaign initiated in August in the country after evidence of waning immunity of the mRNA vaccine (Pfizer-BioNTech). At the time, the Delta variant was responsible for more than 99% of cases, and numbers were surging. Many cases occurred in vaccinated individuals.

The United States and other countries have begun administering boosters as well, and with use of different kinds of vaccines, data will be critical to determine whether the same effects are seen across booster types.

In this study, the population included 306,710 members of Maccabi Healthcare Services (55% female). The patients received either two or three doses of the Pfizer vaccine. Those who were included in the study did not test positive on PCR for SARS-CoV-2 before the start of the follow-up period.

During the study period, 500,232 PCR tests were performed. Of those who were tested, 227,380 persons received two doses, and 272,852 received three doses. In the two groups, positive test results were seen in 14,989 (6.6%) and 4941 (1.8%), respectively.

"The positive percentage was highest among those who had not received a booster and among those who had received a booster in the previous 7 days, and was lowest among individuals who had received the booster more than 2 weeks prior," the report states.

Effectiveness Increases Over Weeks

The effectiveness of the booster appears to increase over the first few weeks. There was a small reduction in the odds of testing positive in the first week (12%; 95% CI, 8% – 17%), a moderate marginal measure of effectiveness in week 2 (58%; 95% CI, 56% – 61%), and high effectiveness in days 14 through 20 and beyond (85%; 95% CI, 83% – 86%).

Further work is needed to see how long immunity lasts, the authors write.

The retrospective case-control study used two designs: a test-negative design and a matched case-control design. Participants' data were from the national database of Maccabi Healthcare Services, an Israeli healthcare maintenance organization covering 2.5 million members.

Dr William Schaffner

William Schaffner, MD, infectious disease specialist at Vanderbilt University Medical Center in Nashville, Tennessee, told Medscape Medical News the data from Israel are particularly important because researchers there can conduct large studies with one primary vaccine and an integrated healthcare system, which yield consistent data.

"It's very good news, but it's a little limited because it's a short-term study. But we'll take what we can get," he said.

While those in infectious disease are not surprised by the positive results, the hard data strengthen the message for the public, Schaffner said.

Vaccine "Annoyance"

Whether this latest news can cut through COVID fatigue and "COVID annoyance" and encourage more people to get boosters remain to be seen, he said.

"The average person thinks we keep giving them homework assignments," Schaffner said. The message they get is, "Oh good, you got an 85 on your last test, but here's some new information you've got to learn."

Another unknown is the coming of the Omicron variant and whether protection levels from the current vaccines will be maintained.

Reuters reported late last week that BioNTech said it expects more data on Omicron within 2 weeks to help determine whether its vaccine, which was produced with Pfizer, would have to be altered.

As Medscape Medicdal News reported, Pfizer and BioNTech plan to apply for US Food and Drug Administration (FDA) approval this week for a booster COVID-19 vaccine for 16- and 17-year-olds.

Reportedly, the FDA could authorize the extra dose within a week. If approved, it would be the first booster for those younger than age 18.

Moderna told Reuters in a statement that it is working to develop a booster tailored to the new variant, that it has also been testing a higher dose of its existing booster, and that it is studying other formulations to protect against multiple variants.

Co-author Daniel Weinberger, MD, reported receiving consulting fees from Pfizer, Merck, Affinivax, and Matrivax outside the submitted work and is principal investigator on grants from Pfizer and Merck to Yale University for work unrelated to this article. Full author disclosures are available with the original article. Ray and Schaffner report no relevant financial relationships.

JAMA Intern Med. Published online November 30, 2021. Full text

Marcia Frellick is a freelance journalist based in Chicago. Follow her on Twitter at @mfrellick.

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