Recently, Pfizer Inc. and BioNTech SE announced updated data from a phase II/III clinical trial demonstrating a strong, neutralizing immune response 1 month after a 30-mcg booster dose of the companies’ Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine (Pfizer-BioNTech COVID-19 vaccine, bivalent [original and Omicron BA.4/BA.5]). Immune responses against BA.4/BA.5 sublineages were considerably greater for those who received the bivalent vaccine compared with the companies’ original COVID-19 vaccine, with a comparable safety and tolerability profile between both vaccines.
These results reinforced the previously reported early clinical data measured 7 days after a booster dose of the bivalent vaccine, as well as the preclinical data, and suggested that a 30-mcg booster dose of the Omicron BA.4/BA.5-adapted bivalent vaccine may induce a greater level of protection against the Omicron BA.4 and BA.5 sublineages than the original vaccine.
Albert Bourla, chairman and CEO of Pfizer, stated, “As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating Omicron BA.4 and BA.5 sublineages. These updated data also provide confidence in the adaptability of our mRNA platform and our ability to rapidly update the vaccine to match the most prevalent strains each season.”
Ugur Sahin, MD, CEO and cofounder of BioNTech, stated, “These data demonstrate that our BA.4/BA.5-adapted bivalent vaccine works as conceptually planned in providing stronger protection against the Omicron BA.4 and BA.5 sublineages. In the next step and as part of our science-based approach we will continue to evaluate the cross-neutralization of the adapted vaccine against new variants and sublineages. Our goal is to provide broader immunity against COVID-19 caused by SARS-CoV-2, including Omicron and other circulating strains.”
For the analyses, sera were collected before (baseline) and 1 month after administration of a 30-mcg booster dose (fourth dose) of the companies’ Omicron BA.4/BA.5-adapted bivalent vaccine. A subset of individuals, equally stratified between those who had evidence of prior SARS-CoV-2 infection and those who did not, was selected for subjects aged 18 to 55 years (n = 38) and those older than age 55 years (n = 36). A comparator group of participants aged older than 55 years (n = 40) who received a 30-mcg booster dose (fourth dose) of the companies’ original COVID-19 vaccine as part of a prior study was randomly selected, while confirming the same equal stratification.
Participants receiving the bivalent vaccine had their prior booster dose roughly 10 to 11 months earlier, whereas those who received the original vaccine had their prior booster dose around 7 months earlier. Despite this difference, prebooster antibody titers were comparable for both.
The results revealed that among the overall study population who received the Omicron BA.4/BA.5–adapted bivalent vaccine, there was a substantially greater increase in Omicron BA.4/BA.5–neutralizing antibody titers compared to prebooster levels. For individuals aged 18 to 55 years, the geometric mean titer (GMT) against Omicron BA.4/BA.5 was 606, representing a 9.5-fold rise (95% CI: 6.7, 13.6) from prebooster levels. For individuals aged older than 55 years, the GMT was 896, representing a 13.2-fold rise (95% CI: 8.0, 21.6) from prebooster levels. By contrast, participants aged older than age 55 years who received a 30-mcg booster dose of the companies’ original COVID-19 vaccine had a lower neutralizing antibody response against Omicron BA.4/BA.5 measured 1 month post booster. For these participants, the GMT was 236, representing a 2.9-fold rise (95% CI: 2.1, 3.9). Therefore, the Omicron BA.4/BA.5 neutralizing antibody titers were almost fourfold greater for the bivalent vaccine compared with the companies’ original COVID-19 vaccine in individuals aged older than 55 years.
Additionally, when assessing those with or without evidence of prior SARS-CoV-2 infection who received a booster dose of the bivalent vaccine, there was a considerable increase in neutralizing antibodies against Omicron BA.4/BA.5 in both groups, which was greater in those without prior infection. These data emphasized the potential benefit of the bivalent vaccine for all populations regardless of previous SARS-CoV-2 infection. The safety profile remains favorable for the bivalent vaccine and consistent with the original vaccine.
Pfizer and BioNTech are continuing to monitor immunogenicity of the BA.4/BA.5 bivalent booster against emerging Omicron subvariants. The companies also initiated a phase I/II/III trial in September 2022 to evaluate the safety, tolerability and immunogenicity of different doses and dosing regimens of the companies’ Omicron BA.4/BA.5–adapted bivalent vaccine among children aged 6 months through 11 years.
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