In a study conducted at the Mayo Clinic, USA, scientists have investigated the long-term efficacy of the mRNA-based coronavirus disease 2019 (COVID-19) vaccine BNT162b2 (Pfizer/BioNTech) against symptomatic disease.
The findings reveal that although breakthrough infections occur in fully vaccinated individuals, the vaccine remains effective against symptomatic COVID-19 several months after full vaccination. The study is currently available on the medRxiv* preprint server.
In the USA, three COVID-19 vaccines including BNT162b2 (Pfizer-BioNTech), mRNA1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson/Janssen) have received emergency use approval (EUA) by the US Food and Drug Administration (FDA) by February 2021. According to the Centers for Disease Control and Prevention (CDC) report, more than 445 million vaccine doses have been administered to over 205 million people by September 2021 in the USA. Given its high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic COVID-19, the mRNA vaccine BNT162b2 has recently received full approval by the FDA. However, with an increasing prevalence of the delta variant, several vaccine-breakthrough cases have been reported across the country.
Vaccine-breakthrough cases can result from various factors, including waning vaccine efficacy, removal of restriction on non-pharmacological control measures (mask-wearing, physical distancing, and movement restriction), or the emergence of vaccine-resistant viral variants. To break the chain of transmission, it is thus important to evaluate the durability of COVID-19 vaccines and implement appropriate strategies.
In the current study, the scientists have examined the durability of protection offered by BNT162b2 against laboratory-confirmed symptomatic SARS-CoV-2 infection.
The study was conducted on fully vaccinated people who were tested at the Mayo Clinic for suspected symptomatic SARS-CoV-2 infection. As per the general protocol, two doses of the BNT162b2 vaccine are administered at an interval of 18 – 28 days. People who were vaccinated between February and August 2021, were included in the analysis.
The scientists conducted a test-negative case-control analysis to assess the durability of vaccine efficacy. Specifically, they used conditional logistic regression models to assess the probability of symptomatic COVID-19 and non-COVID-19 hospitalization (negative control) after full vaccination at specific time points: 30, 60, 90, 120, and 150 days after full vaccination.
The analysis was conducted on 11,606 people who were fully vaccinated with BNT162b2 and subsequently underwent PCR-based SARS-CoV-2 testing at the Mayo Clinic. Of these people, 670 tested positive for SARS-CoV-2. The final analysis included 652 people who had a positive test result after full vaccination (cases) and 5946 people who had a negative test result after full vaccination (controls).
The findings revealed that the risk of symptomatic SARS-CoV-2 infection increases with time elapsed since the last vaccination. In fully vaccinated people, no significant correlation was observed between the risk of infection and age, sex, race, and ethnicity. However, a reduction in the risk of non-COVID-19 hospitalization was observed with time since the last vaccination. This observation suggests that the confounding factors may influence the regression logistic model to provide an underestimated information about waning vaccine efficacy.
Risk of SARS-CoV-2 infection after first-dose vaccination
The analysis involved 15,180 people who underwent COVID-19 testing after receiving the first dose of the BNT162b2 vaccine. A total of 1061 people were identified as positive cases. The findings revealed that the risk of infection was lower after 150 days of first-dose vaccination compared to that after 4 days of first-dose vaccination.
Furthermore, the scientists conducted a separate set of analyses by considering the time of vaccination and the incidence of COVID-19 in a given region at the time of testing. These analyses involved 974 people with a positive result and 11,371 people with a negative test result who were vaccinated with the first dose on or after January 1, 2021, and were potentially at risk of infection at the time of full vaccination. In this analysis, no correlation was observed between the risk of non-COVID-19 hospitalization and the time since the last vaccination. Importantly, the findings revealed that the risk of infection increases by 7-fold and 10-fold after 120 and 150 days of full vaccination, respectively, compared to that at the time of full vaccination. This indicates a waning vaccine immunity with time.
The study indicates that the BNT162b2-induced immunity against symptomatic COVID-19 gradually declines with time. Based on the findings, the scientists emphasize on administering a third booster dose, developing new vaccines against emerging variants, and implementing non-pharmacological control measures.