Booster Vaccinations in Israel Increased Protection against COVID-19

Israel was the first country to make a third booster dose of an mRNA vaccine against COVID-19 available for the elderly, before expanding to those 12 years or older, and a new large population study of the initial offering confirms that it reduced infection rate compared with a 2-dose vaccination regimen.

In the study report, lead author Yinon Bar-On, MSc, Weizmann Institute of Science, Rehovot, Israel, and colleagues recount that Israel had addressed an increase in cases attributed to the Delta variant by approving the third dose for high-risk populations on July 12, and then for those 60 years of age or older on July 30.

Although the action was based on evidence that the booster of the Pfizer-BioNTech BNT162b2 vaccine increases antibody neutralization levels by an approximate factor of 10 compared with levels after the 2nd dose, Bar-On and colleagues point out that it remained to be determined whether that would correspond to increased protection.

“It is thought that increased neutralization titer could lead to increased protection against infection and severe illness,” Bar-On and colleagues indicated. ”However, in terms of real-world effectiveness, the size of such an effect remains unclear.”

For that real-world data, the investigators accessed records from the Israeli Ministry of Health database for over 1 million persons who were 60 years of age or older and had received the 2-dose vaccination (1,137,804 participants met inclusion criteria).They then compared infection rates during the study period from July 30 through August 2021 between those who did or did not receive a third dose. The booster had been administered at least 5 months after a 2-dose vaccination. The rate of infections was calculated from confirmed cases which occurred at least 12 days after the respective vaccinations, in the period of expected immunologic efficacy.

The non-booster group included approximately 5.2 million person-days of risk, with 4439 confirmed infections and 294 cases of severe illness.The booster group included 10.6 million person-days of risk with 934 confirmed infections and 29 cases of severe illness.

The investigators reported the confirmed infection rate was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% Confidence Interval [CI] 10.4-12.3). The absolute between-group difference in rate of confirmed infection was 86.6 infections per 100,000 person-days.

The relative rate of severe illness was further lowered in the booster group relative to the nonbooster, by a factor of 19.5 (12.9-29.5)The absolute between-group difference in the rate of severe illness was 7.5 cases per 100,000 person-days.

“Our findings give clear indications of the effectiveness of a booster dose even against the currently dominant delta variant,” Bar-On and colleagues concluded.“Further studies will help determine the long-term effectiveness of the booster dose against current and emerging variants.”

In an accompanying editorial, The New England Journal of Medicine Editor-in-Chief, Eric Rubin, MD, PhD, and Deputy Editor, Lindsey Baden, MD, discussed the Israel study within an interview conducted by Stephen Morrissey, PhD. Although they note that these data can be difficult to apply to practice, with communities that may engage vaccines and health behaviors differently, the large size of the studied population and analyses conducted to reduce bias support the reliability of the findings.

“The fundamental finding of a differential attack rate of COVID infection in those who received a boost looks pretty real," Baden commented.

Rubin agreed that the benefit was apparent, and particularly notable given that the studied population included immunocompromised individuals along with the elderly who were the in the first group to receive the third booster dose. That demographic, however, could also limit generalizing the findings, he cautioned.

"What that would mean for the rest of the population is not so clear," Rubin said. "It may be that there isn't that much of an effect for everybody else, and there's no way of telling from these population level data if that is true."

"So I think there are more important data to come," he added.

With the expansion of booster vaccinations to the wider population in Israel, and the current discussions about which populations in the US should have that access, Rubin offered a final caution."It's also important to remember that these are the data upon which people are acting right now.They're making important public health decisions, and I think that everyone should know that the data aren't perfect."

Although these data are not from randomized controlled trials which supported the initial vaccinations, Rubin recognized that these are the available data. "We're going to have to be using incomplete data or imperfect data to inform what we do," he acknowledged.