Moderna’s bivalent COVID-19 vaccine has bettered the antibody response of Spikevax against omicron when given as a booster, offering encouragement to the biotech as it races toward phase 2/3 data that will shape its offering for the next season of jabs.
The clinical data are on the bivalent vaccine Moderna developed in response to the beta variant, not the omicron-specific booster it is testing in another phase 2/3 clinical trial. However, the readout still offers encouragement for the omicron program, which has supplanted the bivalent beta vaccine as Moderna’s priority variant candidate.
In the beta booster study, 895 people who had previously received a primary two-jab course of Spikevax received one of two doses of the bivalent shot. The beta bivalent vaccine contains equal amounts of two spike protein mRNA sequences: one for ancestral SARS-CoV-2, and one for the beta variant.
Compared to people who received a Spikevax booster, the clinical trial participants had higher antibody responses for ancestral SARS-CoV-2, beta, omicron and delta variants 28 days after being boosted. The bivalent study population still had higher antibody responses for ancestral SARS-CoV-2, beta and omicron 180 days after receiving their boosters. Neutralizing antibody titers were highest in recipients of 100-μg doses, but Moderna focused on the more tolerable 50μg, the dose used in the Spikevax booster.
Beta and omicron share key antibody escape site mutations, pointing to a potential explanation for why the bivalent vaccine performed better against the latter variant than Spikevax did. Omicron-specific antibody geometric mean titers in participants who received 50 μg of the bivalent booster were twice that of the Spikevax control at Day 28. Antibody levels fell sharply by Day 180 but remained well above the control.
In discussing why the bivalent antibody responses were consistently higher against all forms of the virus at Day 28, the researchers said “it is conceivable that the presentation of multiple antigens following the bivalent booster vaccine induces further maturation and evolution of the humoral response.” That idea remains unproven, though.
The hypothesis offers encouragement as Moderna closes in on the release of data from a phase 2/3 trial of its omicron-specific booster. Like the beta booster, the omicron candidate features two spike protein mRNA sequences. As one of the sequences is specific to omicron, the booster could trigger a stronger antibody response against the variant that is now dominant around the world.
Moderna expects to share initial data from the omicron booster trial in the second quarter. The results will shape Moderna’s decision about which vaccine to put forward for booster programs in the fall.