Publication date: May 29, 2025

COVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB. 1.5 and JN. 1 variants, as monovalent and bivalent formulations. Preclinical studies in mice showed that ARVAC XBB. 1.5 and JN. 1 monovalent vaccines induced strong neutralizing antibodies against XBB and JN. 1 lineages, though with limited efficacy against phylogenetically distant variants. By contrast, bivalent formulations combining Gamma antigen with either XBB. 1.5 or JN. 1 antigens demonstrated superior cross-neutralizing activity, covering variants from Ancestral to JN. 1. Additionally, Gamma-containing bivalent vaccines elicited neutralizing antibodies against SARS-CoV-1, highlighting their potential for broad-spectrum immunity. Cellular immune studies confirmed robust CD4 T cell activation across all formulations. These findings support the continued adaptation of ARVAC to current circulant variants and propose ARVAC bivalent vaccines containing the Gamma antigen as a strategy for induction of pan-sarbecovirus immunity.

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