Pfizer and BioNTech Omicron-Adapted Bivalent Booster Shows Significantly Higher Immune Response in Adults

Data from a phase 2/3 clinical trial showed a neutralizing immune response 1 month following a 30-µg booster dose of the Pfizer and BioNTech Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine.

The immune responses produced against BA.4/BA.5 sublineages were significantly higher for individuals administered the bivalent vaccine compared to the companies’ original COVID-19 vaccine, with a similar safety and tolerability profile.

The data from the current trial mirror previously reported early clinical trial findings that analyzed the response 7 days following a booster dose of the bivalent vaccine. These findings indicate that a 30-µg booster dose of the Omicron BA.4/BA.5-adapted bivalent vaccine may produce a higher level of protection against the Omicron BA.4 and BA.5 sublineages than the original vaccine, according to Pfizer and BioNTech.

“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,” said Albert Bourla, chairman and chief executive officer, Pfizer, in a press release. “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.”

The investigators drew sera before and 1 month following administration of the fourth booster dose of 30-µg of the Omicron BA.4/BA.5-adapted bivalent vaccine. A subset of patients in the trial were evenly stratified between individuals with evidence of prior SARS-CoV-2 infection and those who were not infected. The groups included individuals 18 to 55 years of age and older than 55 years of age. A comparison group of individuals older than 55 years of age were randomly selected to receive a 30-µg booster dose of the original COVID-19 vaccine as part of a prior study.

Individuals who were administered the bivalent vaccine had their prior booster dose approximately 10 to 11 months earlier, whereas individuals administered the original vaccine received their booster dose approximately 7 months prior. The pre-booster antibody titers were similar for both despite the difference, according to the investigators.

In the overall study population, individuals administered the Omicron BA.4/BA.5-adapted bivalent vaccine showed a substantially greater increase in Omicron BA.4/BA.5-neutralizing antibody titers compared to pre-booster levels. The geometric mean titer (GMT) against Omicron BA.4/BA.5 was 606 from pre-booster levels for those 18 to 55 years of age.

Among those older than 55 years of age, the GMT was 896, which represents a 13.2-fold rise from pre-booster levels. Conversely, individuals over 55 years of age administered a 30-µg booster dose of the original COVID-19 vaccine had a lower neutralizing antibody response vs Omicron BA.4/BA.5 measured 1 month post booster.

GMT was 236 for these participants, which represents a 2.9 increase. In total, the Omicron BA.4/BA.5 neutralizing antibody titers were approximately 4-fold higher for the bivalent vaccine vs the original COVID-19 vaccine in those over 55 years of age.

When the researchers analyzed individuals with or without evidence of prior SARS-CoV-2 infection who were administered a booster dose of the bivalent vaccine, there was a significant increase in neutralizing antibodies against Omicron BA.4/BA.5 across both groups, which was higher among individuals without prior infection.

The data show the potential benefit of the bivalent vaccine for all populations, regardless of whether they had a prior SARS-CoV-2 infection. The safety profile remained favorable for the bivalent vaccine and was consistent with the original vaccine, according to Pfizer and BioNTech.

REFERENCE

Pfizer and BioNTech Announce Updated Clinical Data for Omicron BA.4/BA.5-Adapted Bivalent Booster Demonstrating Substantially Higher Immune Response in Adults Compared to the Original COVID-19 Vaccine. Pfizer. November 4, 2022. Accessed November 4, 2022. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-updated-clinical-data-omicron