Protection by a Fourth Dose of BNT162b2 against Omicron in Israel

Abstract

Background On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19). Methods Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day. Results The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks. Conclusions Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

“…Our results for immunogenicity are also consistent with the little observational evidence on vaccine effectiveness available from Israel, which indicates increased protection against symptomatic infection and severe illness from a fourth-dose booster. 6 , 7 In our study, half-dose mRNA-1273 appeared to have higher immunogenicity than full-dose BNT162b2, which was also seen in the Israeli study, 6 although the two groups in the Israeli study were not randomised. This result might be due to a heterologous schedule effect or the vaccine dose.…”

“…Observational data from Israel have shown a boosting effect on immunogenicity 6 and moderate protection against symptomatic infection from a fourth dose of mRNA COVID-19 vaccines administered approximately 4 months after a third dose. 7 , 8 The clinical need, timing, and dose of the fourth COVID-19 vaccine remain uncertain, 9 as does the gain in vaccine effectiveness compared with a third dose. Given the urgent need for data to inform policy on additional booster doses, the COV-BOOST trial 1 of third-dose booster vaccines for COVID-19 was extended to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19 administered approximately 7 months following a third dose of BNT162b2 (Pfizer-BioNTech).…”

Factors associated with the risk perception of COVID-19 infection and severe illness: A cross-sectional study in Japan

“…In addition, the effectiveness of the COVID-19 vaccine against COVID-19 infection and onset has been shown to decline over several months ( Tartof et al, 2021 ), and a third dose of vaccination is being offered in some countries ( Centers for Disease Control and Prevention (CDC), 2021 , Ministry of Health , National Health Service (NHS) ). As of April 2022, some countries also have begun offering fourth doses of vaccination ( Bar-On et al, 2022 ). Several studies have warned that if various activity restrictions are lifted before vaccination rates are high enough, the number of cases will rise again ( Centers for Disease Control and Prevention (CDC) , Public Health England , World Health Organization, 2020a , World Health Organization, 2020b , World Health Organization, 2020c ).…”

A fourth dose of Omicron RBD vaccine enhances broad neutralization against SARS‐CoV‐2 variants including BA.1 and BA.2 in vaccinated mice

“…The rates of confirmed SARS‐CoV‐2 infection and severe COVID‐19 were both lower than those after only three doses during the Omicron‐dominated period. 19 However, a recent study raised the concern of this homologous booster immunization with the original WT virus sequence. Wang et al stated that the peak level of RBD‐nAbs elicited by a fourth dose of homologous SARS‐CoV‐2 inactivated vaccine was inferior to that induced by the former three doses and proposed that the next‐generation vaccine carrying epitopes of variants would be a future direction for the booster vaccination.…”