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Moderna’s Bivalent COVID-19 Booster Elicits Superior Antibody Responses

Moderna’s new bivalent COVID-19 booster, which includes 25 micrograms each of messenger RNAs from the Wuhan-Hu-1 and Omicron B.1.1.529 variants of SARS-CoV-2, elicited antibody responses that were superior to those elicited by the original vaccine.


Moderna’s bivalent COVID-19 vaccine containing the Omicron variant elicited superior neutralizing antibody responses against the Omicron variant than the original vaccine, an ongoing Phase 2-3 clinical trial found.

The study, published in the New England Journal of Medicine, evaluated the safety, reactogenicity and immunogenicity of the bivalent vaccine, which includes 25 micrograms each of messenger RNAs from the Wuhan-Hu-1 and Omicron B.1.1.529 variants of SARS-CoV-2.

Two groups were included in the study, with 437 participants receiving a 50-microgram dose of the the bivalent vaccine, mRNA-1273.214, and 377 receiving a 50-microgram dose of the original mRNA-1273 vaccine as a second booster dose. All participants had received the original series of two 100-microgram doses of the vaccine and a 50 micgrogram booster.

“The bivalent Omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against Omicron that were superior to those with mRNA-1273, without evident safety concerns,” the study authors wrote, led by Spyros Chalkias, MD, Moderna.

All study participants had seroresponses against the ancestral SARS-CoV-2 virus 28 days after receiving the booster doses.

Those who received the bivalent vaccine had geometric mean titers of neutralizing antibodies against the BA.1 Omicron subvariant of 2,372.4 compared with 1,473.5 among those who received the original vaccine as a second booster, exceeding the recommended superiority criteria. Against the BA4 and BA5 subvariants, geometric mean titers were 727.4 in the bivalent vaccine group and 492.1 in the other group.

The updated booster also elicited higher binding antibody responses against other variants, including Alpha, Beta, Gamma and Delta.

Adverse reactions were similar for both groups, with the most frequent local adverse reaction in both groups being injection-site pain. Systemic reactions, including fatigue, headache, myalgia and arthralgia also were seen in both groups. Adverse reactions were predominantly mild to moderate, with no Grade 4 adverse events in either group.

Serious adverse events were reported in two participants in the bivalent vaccine group and one in the other group, but not were related to the vaccination. They were prostate cancer, traumatic fracture and spinal osteoarthritis. The investigators reported no deaths and no occurances of myocarditis or pericarditis.

“Overall, the safety and reactogenicity of mRNA-1273.214 after three previous mRNA-1273 doses administered at intervals of at least 3 months are reassuring and are similar to those previously reported for the bivalent beta-containing candidate, mRNA-1273.211, which had a safety profile similar to that of mRNA-1273 through 6 months after vaccination,” the study authors wrote.

Limitations of the study include a lack of randomization. More research is needed to understand cellular responses to the vaccine.

Pfizer and BioNTech also have released early data from a phase 2-3 of their bivalent COVID-19 vaccine adapted to include the BA4 and BA4 Omicron subvariants. That study found that a 30-microgram booster dose provided better protection against those variants than the original vaccine.

The FDA authorized the bivalent mRNA COVID-19 vaccines from Moderna and Pfizer-BioNTech for children as young as 6 and 5 respectively on Oct. 12 after granting Emergency Use Authorization for the updated boosters for adults in late August.

“As we head into fall and begin to spend more time indoors, we strongly encourage anyone who is eligible to consider receiving a booster dose with a bivalent COVID-19 vaccine to provide better protection against currently circulating variants,” FDA Commissioner Robert M. Califf, MD, said in a statement at the time.

The vaccines were authorized based on extensive safety and effectiveness data from prior vaccines, which are similar to the updated vaccines, and on nonclincal data while research continued.