Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years

Area of Science:

• Vaccinology
• Immunology
• Virology

Background:

• Emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates sequence-adapted vaccines.
• Protection against coronavirus disease 2019 (COVID-19) requires updated vaccine strategies.

Purpose of the Study:

• To evaluate the superiority and noninferiority of omicron BA.1-adapted BNT162b2 vaccines compared to the original BNT162b2 vaccine.
• To assess neutralizing activity against ancestral and omicron strains (BA.1, BA.4, BA.5, BA.2.75).
• To evaluate the safety profile of the adapted vaccines.

Main Methods:

• Phase 3 trial involving adults over 55 previously vaccinated with three BNT162b2 doses.
• Random assignment to receive BNT162b2, monovalent BA.1-adapted BNT162b2, or bivalent BA.1-adapted BNT162b2 vaccines at different doses.
• Assessment of 50% neutralizing titer (NT50) against BA.1 and ancestral strains, seroresponse, and immune responses against subvariants.

Main Results:

• Bivalent BA.1 and 60 μg monovalent BA.1 vaccines demonstrated superior neutralizing activity against BA.1 compared to BNT162b2.
• Adapted vaccines were noninferior to BNT162b2 for seroresponse against BA.1 and neutralizing activity against the ancestral strain.
• Neutralizing titers against BA.4-BA.5 and BA.2.75 were numerically higher with 30 μg bivalent BA.1.
• Safety profiles were similar, though higher adverse event rates were noted in specific monovalent and bivalent groups.

Conclusions:

• Omicron BA.1-adapted vaccines (monovalent and bivalent) exhibit a safety profile comparable to BNT162b2.
• These adapted vaccines induce substantial neutralizing responses against ancestral and omicron BA.1 strains.
• The vaccines show a lesser degree of neutralization against BA.4, BA.5, and BA.2.75 strains, indicating potential for broader protection.