Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial

Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding the ancestral SARS-CoV-2 and Beta variant spike proteins, as 50-mu g (n = 300) and 100-mu g (n = 595) first booster doses administered approximately 8.7-9.7 months after the mRNA-1273 primary vaccine series (). The primary objectives were to evaluate the safety and reactogenicity of mRNA-1273.211 and to demonstrate non-inferior antibody responses compared to the mRNA-1273 100-mu g primary series. Additionally, a pre-specified immunogenicity objective was to demonstrate superior antibody responses compared to the previously authorized mRNA-1273 50-mu g booster. The mRNA-1273.211 booster doses (50-mu g or 100-mu g) 28 days after immunization elicited higher neutralizing antibody responses against the ancestral SARS-CoV-2 and Beta variant than those elicited 28 days after the second mRNA-1273 dose of the primary series (). Antibody responses 28 days and 180 days after the 50-mu g mRNA-1273.211 booster dose were also higher than those after a 50-mu g mRNA-1273 booster dose () against the ancestral SARS-CoV-2 and Beta, Omicron BA.1 and Delta variants, and all pre-specified immunogenicity objectives were met. The safety and reactogenicity profile of the bivalent mRNA-1273.211 booster (50-mu g) was similar to the booster dose of mRNA-1273 (50-mu g). Immunization with the primary series does not set a ceiling to the neutralizing antibody response, and a booster dose of the bivalent vaccine elicits a robust response with titers that are likely to be protective against COVID-19. These results indicate that bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants. A bivalent vaccine encoding the ancestral and Beta variant SARS-CoV-2 spike proteins boosts neutralizing antibody responses against multiple viral variants, suggesting that a bivalent approach is an effective strategy to broadly enhance protection against COVID-19.

Automated summary

The study suggests that a bivalent COVID-19 vaccine as a booster can induce potent and broad antibody responses against multiple viral variants, providing a new tool to respond to emerging variants.