Dec. 1, 2021 -- A third (booster) shot of the Pfizer COVID-19 vaccine appears to reverse the waning protection of the first two shots, at least in the short term, according to a new study.

Tal Patalon, MD, with the Kahn Sagol Maccabi Research and Innovation Center in Israel, led a study of 306,710 Israeli adults 40 years and older. The results were published online Tuesday in JAMA Internal Medicine.

The researchers found that the estimated odds of becoming infected with the coronavirus 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 86% reduction in the odds of testing positive after the booster.

“This reduction comes on top of the reduction in the risk conferred by the first two 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, says,

He said the study design -- looking at positive tests as a surrogate of getting infected – was a reasonable approach.

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

“We need to see this work replicated, but it makes sense biologically and it aligns well with our prior work with initial dosing,” Ray says. “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 says. He notes that other vaccines, including those for Hepatitis B, HPV, and shingles, have doses separated by different intervals.

“Vaccinating with that kind of resting period really does tend to generate the best responses,” Ray says.

“I don’t think this study suggests we’ll be getting extra doses every few months,” he says.

Over time, data will help determine the best intervals “and, of course, in the context of the Omicron variant whether this kind of protection extends to something as different as Omicron,” Ray says.

The study will likely help motivate those who run health care systems to consider ramping up efforts to get employees vaccinated with a third dose, he says.

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, a moderate marginal measure of effectiveness in week 2, and high effectiveness in days 14 through 20 and beyond.

More research is needed to see how long immunity lasts, the authors write.

William Schaffner, MD, infectious disease specialist at Vanderbilt University Medical Center in Nashville, says the data from Israel are particularly important because researchers there can do large studies with one primary vaccine and an integrated health care system, which yields 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 says.

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

Vaccine ‘Annoyance’

Whether this latest news can cut through COVID-19 fatigue and “COVID annoyance” and urge more people to get boosters remains to be seen, he says.

“The average person thinks we keep giving them homework assignments,” Schaffner says. 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 current vaccines will maintain protection levels.

Reuters reported late last week that Pfizer and its partner BioNTech expect more data on Omicron within 2 weeks to help determine whether its vaccine would have to be altered.

Pfizer plans to ask the FDA this week to authorize a booster COVID-19 vaccine for 16- and 17-year-olds.

The FDA could reportedly authorize the extra dose within a week. If approved, it would be the first booster for those under age 18.

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