Does COVID-19 vaccine effectiveness wane over time?

A large study conducted in Israel has suggested that the effectiveness of the BNT162b2 vaccine against COVID-19 decreases over time.

The study population comprised 4,791,398 Israeli residents aged <16 years who had been fully vaccinated against COVID-19 with the BNT162b2 vaccine before June 1, 2021 and who were not infected before the July 11–31, 2021 study period, as per the Israeli Ministry of Health national database. Participants were considered completely vaccinated ≥7 days after receipt of second dose with second dose administered 3 weeks post-first dose. To identify waning of vaccine effectiveness, the researchers examined the rates of PCR-confirmed SARS-CoV-2 infection and subsequent COVID-19 disease severity occurring during the study period according to vaccination period and age when the individuals were eligible for vaccination. A total of 13,426 individuals tested positive for SARS-CoV-2, with 403 developing severe disease.

In individuals aged ≥60 years, SARS-CoV-2 infection rates during the study period were higher among those who completed full vaccination during the second half of January 2021 (when this age group was first eligible) compared with those who completed vaccination in March (rate ratio [RR], 1.6, 95 percent confidence interval [CI], 1.3–2.0), April (RR, 2.2, 95 percent CI, 1.6–3.1), or May 2021 (RR, 2.2, 95 percent CI, 1.3–3.6). [N Engl J Med 2021;doi:10.1056/NEJMoa2114228]

Similar results were observed among individuals aged 40–59 years, with those fully vaccinated in February 2021 (when they were first eligible) having a higher infection rate than those fully vaccinated in April (RR, 1.7, 95 percent CI, 1.4–2.1) or May (RR, 2.1, 95 percent CI, 1.4–3.0). Likewise, higher infection rates were noted among individuals aged 16–39 years who were fully vaccinated upon eligibility in March 2021 compared with May 2021 (RR, 1.6, 95 percent CI, 1.3–2.0).

The waning effectiveness appeared to affect likelihood of severe COVID-19 disease*, with higher rates noted among those who completed vaccination upon eligibility vs in March 2021 (RR, 1.8, 95 percent CI, 1.1–2.9 [age ≥60 years] and RR, 2.2, 95 percent CI, 0.6–7.7 [age 40–59 years]).

The success of a mass vaccination programme against COVID-19 is curtailed by breakthrough infections, particularly due to the emergence of new variants of the virus and waning vaccine effectiveness, said the researchers.

“The appearance and rapid predominance of the delta variant in June 2021 resulted in a dramatic increase in the number of new SARS-CoV-2 infections among fully vaccinated persons, which aroused concern regarding decreased efficacy of the vaccine over time,” they continued.

One potential reason for this waning effectiveness could be “a correlated time-dependent reduction in neutralization titres” which results of serologic studies have demonstrated. [Nat Med 2021;27:1205-1211]

In addition to these findings, comparison of vaccinated and unvaccinated individuals based on data from the Israeli Central Bureau of Statistics showed that individuals who were vaccinated were protected even after 6 months compared with unvaccinated individuals, though vaccine effectiveness was lower than it was close to vaccination date.

“Understanding the extent of waning immunity is critical for policy making, especially regarding vaccination strategies,” the researchers said.

The results led to the approval of the third or booster dose of the vaccine to individuals in Israel who had been vaccinated ≥5 months prior. “The findings also suggest the need to follow the effects of waning immunity closely and to inform policymakers worldwide who are facing decisions regarding the administration of booster vaccinations,” they concluded.