Third vaccine dose reduces transmission and severe COVID-19 nationwide in Israel

Following the successful administration of two doses of the Pfizer BNT162b2 vaccine to most eligible adults in Israel, the country saw a remarkable drop in the number of cases of coronavirus disease 2019 (COVID-19) and hospitalizations. However, this changed as the country opened up, leading to a surge in new cases driven largely by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant.

Study: BNT162b2 vaccine booster dose protection: A nationwide study from Israel. Image Credit: PalSand/ Shutterstock

A third dose of the vaccine was approved, especially for the elderly who had been the first to receive the vaccinations initially and were therefore at the highest risk of having waning antibody levels. A new preprint on the medRxiv* server investigates the success of this strategy on a nationwide scale in reducing viral spread and the number of severe COVID-19 cases, even in the presence of a delta-driven increase in total infections.

A preprint version of the study is available on the medRxiv* server while the article undergoes peer review.


The vaccination campaign in Israel was efficient, with half of its population being completely vaccinated at the end of March 2021. This was accompanied by a reduction in COVID-19 cases from 900 per million to less than two from January to June 2021.

However, the delta variant of the virus brought back the cases with its higher transmissibility, partial resistance to neutralization by the antibodies elicited by earlier strains of the virus, and waning antibody levels over time. The resulting decline in vaccine efficacy has been responsible for the unforeseen crisis again looming in Israel.

However, identifying waning antibody levels as a risk factor for a delta surge also suggested a way out. Early studies showed that a booster dose of the BNT162b2 vaccine increased the neutralizing antibody levels ten-fold compared to the levels achieved after the second dose.

Therefore, the Israeli government quickly rolled out a vaccine booster dose, prioritizing high-risk populations but covering the whole community of the elderly (people over 60 years) afterward.

The program was approved on July 12, 2021, for the high-risk groups and other older adults on the 30th of the month.

What did the study show?

The current study was a real-world efficacy study to show the effect of this type of boost in vaccine-elicited antibody levels. The researchers compared people aged 60 and above, those who had received two doses of the vaccine, vs. those who had received the booster at least 12 days before the study.

The study design provided time for antibody levels to build up following the booster. The researchers also expected changes in the behavior of those who had received the booster dose, such as staying away from high-risk situations until antibody levels rose and not testing for COVID-19 around the time of the booster.

COVID-19 infections can be confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) testing only a few days after exposure. These reasonable delays made it expedient to delay the investigation into the protection afforded by the booster dose until 12 days, at least, had passed.

The study subjects belonged to the booster and non-booster cohorts, with the second merging into the first as they first got their boosters and then crossed 12 days. The no-booster cohort included about four million person-days. There were 3,473 confirmed cases of COVID-19, with 330 cases of severe COVID-19. The booster cohort included 3.4 million person-days, with just over 300 infections and 32 cases of severe disease.

The differences between the two cohorts included more men, at 50% vs. 43%, more older people, at 60% vs. 47%, more Jewish people at 93% vs. 82%, and more who had been vaccinated in January, at ~80% vs. 40%.

The results showed an 11-fold reduction in confirmed infections following the administration of a booster dose. It also suggested a 15.5-fold reduction in the risk of severe disease.

The protection starts 12 days after vaccination, with a 10-12-fold reduction in risk. This begins early, probably because of the changes in behavior that prevent exposure. As these changes taper off over time, the size of the protective effect also shows a decline until day seven, when it begins to increase again.

What are the implications?

The study suggests a large effect of the booster BNT162b2 vaccine in protecting against confirmed infection and severe illness in the elderly and high-risk population.

The vaccine’s efficacy against the delta strain is restored to its original level of 95% as reported against the alpha variant of the virus. The observed fact that the tendency to go in for PCR testing is low a few days before and after the vaccination date provides a source of low detection of cases. This is corrected over time once the vaccine has been taken.

The study aimed to provide data to assess the value of a third booster-dose vaccine policy for the elderly and those at high risk for severe COVID-19. Therefore, the findings are of value for those countries that are pondering strategies to mitigate the impact of the delta variant.

*Important notice


medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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