Immunogenicity of a Fourth Homologous Dose of NVX-CoV2373

This correspondence presents results from an extension of a phase 2 randomized trial evaluating the immunogenicity of a fourth homologous dose of the NVX-CoV2373 (Novavax) recombinant spike protein vaccine. Using antigenic cartography and validated assays, researchers tracked changes in anti-recombinant spike (rS) IgG and neutralizing antibody titers across ancestral SARS-CoV-2 and Omicron variants BA.1 and BA.4/BA.5. Compared to titers after two doses, the fourth dose substantially decreased antigenic distances and enhanced cross-reactive immunity: IgG factor differences for BA.5 vs. ancestral strain dropped from 4.4 to 1.8, while neutralization gaps narrowed from 33.5 to 3.5. The improved universal-like response is attributed to conserved spike epitopes and the Matrix-M adjuvant’s ability to promote epitope spreading. Authors call for efficacy studies to confirm clinical benefit.

This correspondence presents results from an extension of a phase 2 randomized trial evaluating the immunogenicity of a fourth homologous dose of the NVX-CoV2373 (Novavax) recombinant spike protein vaccine. Using antigenic cartography and validated assays, researchers tracked changes in anti-recombinant spike (rS) IgG and neutralizing antibody titers across ancestral SARS-CoV-2 and Omicron variants BA.1 and BA.4/BA.5. Compared to titers after two doses, the fourth dose substantially decreased antigenic distances and enhanced cross-reactive immunity: IgG factor differences for BA.5 vs. ancestral strain dropped from 4.4 to 1.8, while neutralization gaps narrowed from 33.5 to 3.5. The improved universal-like response is attributed to conserved spike epitopes and the Matrix-M adjuvant’s ability to promote epitope spreading. Authors call for efficacy studies to confirm clinical benefit.