Bivalent mRNA-1273.214 booster offers superior immunogenicity vs original vax

Compared with mRNA-1273, the superiority of the immune response of mRNA-1273.214 was demonstrated against BA.1 (geometric mean ratio [GMR], 1.53 [99 percent confidence interval [CI], 1.41–1.67]).

The noninferiority of the immune response of mRNA-1273.214 against the D614G strain was also demonstrated (GMR, 1.05 [99 percent CI, 0.96–1.15]) vs mRNA-1273.

Incidence rates of symptomatic infection were 15.8 percent and 17.7 percent in the mRNA-1273.214 and mRNA-1273 groups, respectively.

Implication of the study

“mRNA-1273.214 elicited neutralizing antibody responses against BA.1 that were superior to those of mRNA-1273,” said presenting author Dr Ivan Lee from Moderna Inc, Cambridge Massachusetts, US. “The booster was well-tolerated without evident safety concerns.”

“Our findings support the immunogenicity and safety of bivalent vaccines to combat ongoing SARS-CoV-2 variant evolution,” he pointed out.

Compelling need for a vaccine with broader protection

Strategies that broaden protection against SARS-CoV-2 variants are crucial to mitigate COVID-19 disease burden, Lee said.

“In response to the SARS-CoV-2 omicron variant (BA.1), the bivalent mRNA-1273.214 vaccine was developed to contain mRNA encoding the prefusion-stabilized spike glycoprotein of both the SARS-CoV-2 Wuhan Hu-1 strain and the BA.1 variant.”

Lee and his team conducted a phase III, randomized, observer-blind, active-controlled trial to assess the safety and immunogenicity of the mRNA-1273.214 booster in individuals aged 16 years and older in the UK. Demographics and baseline characteristics were balanced. [ECCMID 2023, abstract O0688]

Participants previously received 2 or 3 doses of an authorized/approved COVID-19 vaccine and were randomly assigned 1:1 to receive a 50-µg booster of mRNA-1273.214 or mRNA-1273. Safety and reactogenicity were then evaluated.

The primary immunogenicity objectives were to demonstrate the superiority of mRNA-1273.214-elicited immune responses to BA.1 and the noninferiority of mRNA-1273.214-elicited immune responses to the prototype strain (D614G) at day 29 or month 3 compared with a fourth dose of mRNA-1273 in participants without evidence of baseline SARS-CoV-2 infection.

The secondary objective was the incidence of SARS-CoV-2 infection, results at day 29 were presented by Lee at ECCMID 2023.

Included in the analysis were 1,422 mRNA-1273.214 recipients and 1,402 mRNA-1273 recipients. Both vaccines were generally well-tolerated and no new safety concerns were identified.