Boosting of bivalent Omicron BA.1-adapted BNT162b2 in adults older than 55 years
Introduction
Vaccination remains a critical mitigation tool in the ongoing coronavirus disease 2019 (Covid-19) pandemic. The 30 μg dose of the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech vaccine) encoding the protein spike Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is licensed as a two-dose primary series for persons 12 years of age and older; a phase 2-3 trial conducted early in the pandemic showed 95-100% efficacy with this primary series.
BNT162b2 has provided broad protection in previously dominant SARS-CoV-2 variants of concern, which had relatively low potential to escape vaccine-induced immunity. In contrast, efficacy against mild disease caused by the more antigenically distinct B.1.1.529 (omicron) variant has been markedly reduced. Although the immune escape could be mitigated by a third or fourth dose of vaccine, efficacy against the omicron BA.1 subvariant, including efficacy in preventing severe disease, declined more rapidly than observed for earlier variants of concern.
Because it was desirable to design a sequence-adapted vaccine that would match the circulating variant of interest, an approach supported by regulatory agencies, this trial sought to assess the reinforcement strategies with different dose levels and BNT162b2 vaccines adapted to omicron BA.1. During the course of the assay and due to the high transmissibility of omicron BA.1, other mutations of omicron BA.1 led to the emergence and subsequent dominance of the omicron BA.4 and BA.5 subvariants and the newly identified omicron BA subvariant that they are comparatively even more antigenically distinct from previous SARS-CoV-2 variants of concern than the BA.1 subvariant. 16-18 Therefore, we also evaluated the ability of the BNT162b2 vaccines monovalent and bivalent omicron BA.1 adapted to neutralize BA.4 and BA.5, which encode the same spike sequence, 17 and BA.2.75.
Background
The emergence of immune escape variants of severe acute respiratory syndrome coronavirus 2 justifies the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019.
Methods
In an ongoing Phase 3 trial, adults 55 years and older who had previously received three doses of 30 μg of the BNT162b2 vaccine to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of B.1.1.529 monovalent (omicron) BNT162b2 adapted to BA.1 (monovalent BA.1), or 30 μg (15 μg of BNT162b2+15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2+30 μg of monovalent BA.1); of BNT162b2 adapted to BA.1 (BA.1 bivalent).
Los primary goals were to determine the superiority (relative to 50% of the neutralization titer [NT 50] against BA.1) and non-inferiority (with respect to seroresponse) of BA.1-adapted vaccines to BNT162b2 (30 µg).
And secondary objective was to determine the non-inferiority of bivalent BA.1 to BNT162b2 (30 µg) with respect to neutralizing activity against the ancestral strain. Exploratory analyzes evaluated immune responses against the omicron BA.4, BA.5, and BA.2.75 subvariants.
Results
A total of 1846 participants they were randomized. One month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutralizing activity against BA.1 greater than that of BNT162b2 (30 μg), with geometric mean ratios of NT 50 (GMR) of 1.56 (confidence interval [IC] 95% CI, 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively .
