Waning Immunity after the BNT162b2 Vaccine in Israel

N Engl J Med. 2021 Dec 9;385(24):e85. doi: 10.1056/NEJMoa2114228. Epub 2021 Oct 27.


Background: In December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear.

Methods: We used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors.

Results: Among persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age.

Conclusions: These findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood
  • BNT162 Vaccine / immunology*
  • COVID-19 / epidemiology*
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • Female
  • Humans
  • Immunization, Secondary
  • Immunogenicity, Vaccine*
  • Israel / epidemiology
  • Male
  • Middle Aged
  • Patient Acuity
  • Poisson Distribution
  • Regression Analysis
  • SARS-CoV-2*
  • Socioeconomic Factors
  • Time Factors
  • Vaccine Efficacy*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • BNT162 Vaccine

Supplementary concepts

  • SARS-CoV-2 variants