Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. The omicron BA.1-adapted BNT162b2 vaccine candidates elicited significant neutralizing antibodies against the omicron strains as well as the ancestral strains while maintaining similar safety to the original vaccine.

2. The BA.1-adapted vaccine also induced neutralizing responses against the novel BA.4, BA.5, and BA.2.75 strains.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing public health issue. The BNT162b2 vaccine from Pfizer-BioNTech previously demonstrated effectiveness against previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and proved to be invaluable in the global strategy for combating COVID-19. However, the emergence of the highly transmissible omicron subvariants capable of evading immune responses prompted the need to adapt these vaccines and maintain adequate protection. The current study was an ongoing randomized trial to investigate the safety and efficacy of omicron BA.1-adapted BNT162b2 booster vaccine candidates for fully vaccinated adults older than 55 years. The BA.1-adapted vaccines elicited significant neutralizing antibodies against the omicron BA.1 strain while the bivalent vaccine also induced a response against the ancestral strain. The BA.1-adapted vaccines also induced limited neutralizing responses against other novel omicron BA.4, BA.5, and BA.2.75 subvariants. The main study limitation was its lack of longer-term follow-up amidst the rapidly evolving pandemic and emerging variants. Overall, among fully vaccinated older adults, the BA.1-adapted vaccines demonstrated sufficient safety and efficacy in inducing neutralizing antibody responses against the BA.1 omicron variant and, to a lesser degree, other novel omicron subvariants.

In-Depth [randomized controlled trial]:

The ongoing phase three randomized trial assessing the efficacy and safety of BA.1-adapted BNT162b2 booster vaccines for adults older than 55 years who had been fully vaccinated with three 30µg BNT162b2 doses. Overall, 1,846 participants were randomized 1:1:1:1:1:1 to receive 30µg or 60µg of BNT162b2, 30µg or 60µg of monovalent BA.1-adapted BNT162b2 (monovalent BA.1), or 30µg of (15µg of BNT162b2 + 15µg of monovalent BA.1) or 60µg (30µg of BNT162b2 + 30µg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). The primary objectives were to demonstrate superiority (based on the 50% neutralizing titers against SARS-CoV-2 [NT50]) and noninferiority of the immune response against omicron BA.1 elicited by the monovalent BA.1 or bivalent BA.1 booster compare to BNT162b2 given as a 4th dose. At one month following vaccination, both bivalent BA.1 (30µg and 60µg) and monovalent BA.1 (60µg) showed superior neutralizing activity against BA.1 compared to BNT162b2 (30µg), yielding NT50 geometric mean ratios (GMRs) of 1.56 (95% Confidence Interval [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. With regards to protection against the ancestral strain, bivalent BA.1 (both doses) was noninferior to BNT162b2 (30µg), yielding NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. As an exploratory analysis, neutralizing activity against the novel distinct omicron BA.4, BA.5, and BA.2.75 subvariants were also assessed. The 30µg bivalent BA.1 showed higher neutralizing titers against these subvariants than 30µg BNT162b2. Lastly, both BA.1-adapted vaccines had similar safety profiles to BNT162b2 with injection-site pain and fatigue being the most common adverse events, and no life-threatening reactogenicity was observed. These findings demonstrated that BA.1-adapted boosters had an acceptable safety profile and efficacy against ancestral and omicron BA.1 strains.

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