Booster shot of Pfizer COVID-19 vaccine provides additional protection against SARS-CoV-2 infection

A team of scientists from the USA and Israel has recently highlighted the importance of a third booster dose of the Pfizer/BioNTech coronavirus disease 2019 (COVID-19) vaccine in achieving additional protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study is currently available on the medRxiv* preprint server.


A considerable reduction in the effectiveness of existing COVID-19 vaccines has been witnessed by many countries with the emergence of variants of concern (VOCs) of SARS-CoV-2. These VOCs contain multiple mutations in the spike-coding genetic region associated with improved viral fitness in terms of higher transmissibility, infectivity, immunogenicity, and virulence.

The majority of the available vaccines, including mRNA-based vaccines developed by Pfizer/BioNTech and Moderna, follow a two-dose regimen administered intramuscularly at a fixed interval.

The mass vaccination programs in Israel primarily include the BNT162b2 (Pfizer/BioNTech) vaccine that has shown more than 90% efficacy in preventing symptomatic COVID-19. Despite experiencing a drop in infection rate soon after initiation of vaccination, Israel has faced a sharp rise in new infections, including vaccine breakthrough infections during June – July 2021, because of the predominantly circulating delta variant. The emergence of vaccine breakthrough cases could be due to waning vaccine efficacy or immune escape ability of the delta variant.

Given the waning vaccine efficacy, the Israeli government has initiated a third-booster dose vaccination program in August 2021. Initially, individuals aged 30 years or above and high-risk populations have been prioritized for the third booster dose, which is administered at least 5 months after the second dose immunization. Alike Israel, the USA, and UK governments have decided to immunize their residents with a third booster dose.

The study

In the current study, the scientists have examined the efficacy of a third booster dose of the BNT162b2 vaccine in comparison to the original two-dose regimen. In addition, they have collected all vaccine-related information from Maccabi Healthcare Services, which is the second largest health organization in Israel, covering 2.5 million affiliates.   

Specifically, they have assessed the marginal benefit of the third dose using two complementary approaches: a test-negative design and a matched case-control design.

The case negative design includes individuals with a positive test result for SARS-CoV-2 as “cases” and individuals with a negative test result as “controls.” In the matched case-control design, “cases” have been defined as individuals who tested positive for SARS-CoV-2 after the initiation of third dose vaccination programs on August 1, 2021. These individuals did not have a history of laboratory-confirmed SARS-CoV-2 infection and had received at least two doses of the vaccine. In this design, matched controls have been selected from the entire population.

Important observations

Among individuals who had received two vaccine doses and were tested for SARS-CoV-2, about 5.6% exhibited a positive test result. In contrast, only 3.6% of individuals who had received the third booster dose tested positive for SARS-CoV-2.

The frequency of a positive test result was highest among individuals who had not received the third dose or those who had received the third dose within 7 days of testing positive. In contrast, the frequency was lowest among individuals who had received the third dose more than two weeks before testing positive.      

Although no marginal effectiveness of the third dose compared to the two-dose regimen was observed within 7 days of the administration, about 48% and 79% increase in marginal effectiveness were observed 7 – 13 days and 14 – 20 days after administration of the third booster dose, respectively.

Study significance

The study reveals that the third booster dose of the BNT162b2 vaccine provides additional protection against SARS-CoV-2 infection. Furthermore, the level of protection offered by the third dose gradually increases over time, reaching the highest level around 2 weeks after administration.

Since the booster vaccination program has been introduced only recently, the study could not provide the long-term effectiveness of the third vaccine dose. Moreover, the efficacy of the third dose against severe COVID-19 has not been addressed in the study.

Overall, the study highlights the significance of a third vaccine dose in counteracting waning vaccine immunity.  

*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.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.


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