Importance: Due to the emergence of highly transmissible SARS-CoV-2 variants, evaluation of boosters is needed.
Objectives: Evaluate safety and immunogenicity of 100-µg of mRNA-1273 booster dose in adults.
Design: Open-label, Phase 2/3 study.
Setting: Multicenter study at 8 sites in the U.S.
Participants: The mRNA-1273 100-µg booster was administered to adults who previously received a two dose primary series of 100-µg mRNA-1273 in the phase 3 Coronavirus Efficacy (COVE) trial, at least 6 months earlier.
Intervention: Lipid nanoparticle containing 100-µg of mRNA encoding the spike glycoprotein of SARS-CoV-2 (Wuhan-HU-1).
Main outcomes and measures: Solicited local and systemic adverse reactions, and unsolicited adverse events were collected after vaccination. Primary immunogenicity objectives were to demonstrate non-inferiority of the neutralizing antibody (nAb) response against SARS-CoV-2 based on the geometric mean titer (GMTs) and the seroresponse rates (SRRs) (booster dose vs. primary series in a historical control group). nAbs against SARS-CoV-2 variants were also evaluated.
Results: The 100-µg booster dose had a greater incidence of local and systemic adverse reactions compared to the second dose of mRNA-1273 as well as the 50-µg mRNA-1273 booster in separate studies. The geometric mean titers (GMTs; 95% CI) of SARS-CoV-2 nAbs against the ancestral SARS-CoV-2 at 28 days after the 100-µg booster dose were 4039.5 (3592.7,4541.8) and 1132.0 (1046.7,1224.2) at 28 days after the second dose in the historical control group [GMT ratio=3.6 (3.1,4.2)]. SRRs (95% CI) were 100% (98.6,100) at 28 days after the booster and 98.1% (96.7,99.1) 28 days after the second dose in the historical control group [percentage difference=1.9% (0.4,3.3)]. The GMT ratio (GMR) and SRR difference for the booster as compared to the primary series met the pre-specified non-inferiority criteria. Delta-specific nAbs also increased (GMT fold-rise=233.3) after the 100-µg booster of mRNA-1273.
Conclusions and relevance: The 100-µg mRNA-1273 booster induced a robust neutralizing antibody response against SARS-CoV-2, and reactogenicity was higher with the 100-µg booster dose compared to the authorized booster dose level in adults (50-µg). mRNA-1273 100-µg booster dose can be considered when eliciting an antibody response might be challenging such as in moderately or severely immunocompromised hosts. Trial Registration: NCT04927065.
Key points: Question: What is the safety and immunogenicity of a booster dose of 100 µg of mRNA-1273 in adults who previously received the primary series of mRNA-1273?Findings: In this open-label, Phase 2/3 study, the 100 µg booster dose of mRNA-1273 had a greater incidence of local and systemic adverse reactions compared to a 50 µg booster dose of mRNA- 1273 or after the second dose of mRNA-1273 during the primary series. The 100 µg booster dose of mRNA-1273 induced a robust antibody response against the ancestral SARS-CoV-2 and variants.Meaning: mRNA-1273 100 µg booster dose might be considered when eliciting an antibody response might be challenging, such as in moderately or severely immunocompromised hosts.