Three Large Studies Show Waning Immunity Against SARS-Cov-2 a Few Months After Second Dose of BNT162b2 Vaccine

December 9, 2021

By Denise Baez

Three separate studies published in The New England Journal of Medicine show that immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) significantly diminishes between 2 to 6 months after the second dose of the BNT162b2 mRNA vaccine.

In the first study, Laith J. Abu-Raddad, MD, Weill Cornell Medicine-Qatar, Qatar Doha, Qatar, and colleagues used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of coronavirus disease 2019 (COVID-19) in Qatar from January 1, 2021 to September 5, 2021.

Between December 21, 2020, and September 5, 2021, a total of 947,035 persons received at least 1 dose of BNT162b2, and 907,763 completed the 2-dose regimen. During this period, 564,196 persons received at least 1 dose of the mRNA-1273 COVID-19 vaccine, and 494,859 completed the 2-dose regimen.

As of September 5, 2021, a total of 8,203 SARS-CoV-2 BNT162b2 breakthrough infections had been recorded among participants who received 1 dose of the vaccine, and 10,543 infections among those who received 2 doses. The percentage of all daily diagnosed SARS-CoV-2 infections that were vaccine (BNT162b2 or mRNA-1273) breakthrough infections increased gradually over time and reached 36.4% on September 5, 2021. Most (77.2%) vaccine breakthrough infections were recorded for the BNT162b2 vaccine.

Only 35% of case participants received a diagnosis of SARS-CoV-2 infection on the basis of symptoms. The remaining cases received a diagnosis due to testing for other reasons, such as contact tracing, random testing campaigns, individual requests, and routine healthcare testing.

Effectiveness against any severe, critical, or fatal case of COVID-19 increased rapidly to 66.1% by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months.

“Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose, increased to 36.8% in the third week after the first dose, and reached its peak at 77.5% in the first month after the second dose,” the authors wrote. “Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose…[however], protection against hospitalisation and death persisted at a robust level for 6 months after the second dose.”

In the second study, Yair Goldberg, Technion-Israel Institute of Technology, Haifa, Israel, and colleagues used data on confirmed SARS-CoV-2 infection and severe COVID-19 disease from an Israeli national database for all Israeli residents who had been fully vaccinated with the BNT162b2 vaccine before June 2021. A Poisson regression model was used to compare rates of confirmed SARS-CoV-2 infection and severe COVID-19 among people vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors. 

The main analysis included data from 4,791,398 fully vaccinated adults. Among these, 13,426 had a confirmed SARS-CoV-2 infection and 403 had severe COVID-19 between July 11, 2021, and July 31, 2021, when the Delta variant was prevalent.

Among people aged ≥60 years, the rate of infection in the study 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 [RR], 1.6; 95% confidence interval [CI], 1.3-2.0). Among persons aged 40 to 59 years, the RR 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, 1.4-2.1). Among persons aged 16 to 39 years, the RR 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, 1.3-2.0). The RR 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, 1.1-2.9) among those aged ≥60 years, and 2.2 (95% CI, 0.6-7.7) among those 40 to 59 years.

“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,” the authors concluded.

In the third study, Gili Regev-Yochay, MD, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel, and colleagues conducted a 6-month longitudinal prospective study involving vaccinated healthcare workers who were tested monthly for the presence of anti-spike IgG and neutralising antibodies. The study included 4,868 participants, with 3,808 being included in the linear mixed-model analyses.

The level of IgG antibodies decreased at a consistent rate, whereas the neutralising antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralising antibody titers (Spearman’s rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralising antibody levels depended on the time since receipt of the second vaccine dose.

“In this prospective longitudinal study, we found a significant waning of humoral responses within 6 months after receipt of the second dose of BNT162b2 vaccine in a large cohort of 4,868 participants,” the authors wrote. “We observed a continuous decrease in anti-S IgG titres at a relatively stable rate within 6 months. The decrease in neutralising antibody titres was brisk initially, in the period of up to 70 to 80 days, but slowed thereafter. Antibody titres were associated with age, sex, and coexisting conditions.”

“Published work about many vaccines, such as those against measles, mumps, and rubella, has shown a small decrease each year of 5% to 10% in the neutralising antibody levels,” the authors added. “We found that a significant and rapid decrease in humoral response to the BNT162b2 vaccine was observed within months after vaccination. Strategies to prolong host immunity need to be evaluated in order to protect the population against SARS-CoV-2 and its variants.”

References: https://www.nejm.org/doi/full/10.1056/NEJMoa2114114; https://www.nejm.org/doi/full/10.1056/NEJMoa2114228; and https://www.nejm.org/doi/full/10.1056/NEJMoa2114583

SOURCE: The New England Journal of Medicine