Journal Article Epublish
PubMed: 40442110 DOI: 10.1038/s41541-025-01156-3
Development of bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity.
NPJ Vaccines 10(1):108
Authors: Laura A Bruno, Celeste Pueblas Castro, Agostina Demaría, Lineia Prado, Clara G Fascetto Cassero, Lucas M Saposnik, Federico Páez Córdoba, Juan Manuel Rodriguez, Giulia Piccini, Roberta Antonelli, Giulia Lapini, Nigel Temperton, Sabrina A Del Priore, Andres C Hernando Insua, Ingrid G Kaufmann, Julio C Vega, Juan M Flo, Karina A Pasquevich, Lorena M Coria, Juliana Cassataro
Affiliations
- Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650), Buenos Aires, Argentina.
- Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, San Martín (1650), Buenos Aires, Argentina.
- Laboratorio Pablo Cassará, C1440FFX, Ciudad Autónoma de Buenos Aires, Argentina.
- Fundación Pablo Cassará, Unidad de I+D de Biofármacos, C1440FFX, Ciudad Autónoma de Buenos Aires, Argentina.
- VisMederi Srl, Siena, Italy.
- Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, Kent, ME4 4TB, UK.
- Unidad de I+D, C1408GBV, Ciudad Autónoma de Buenos Aires, Argentina.
- Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650), Buenos Aires, Argentina.
- Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, San Martín (1650), Buenos Aires, Argentina.
- Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Martín (1650), Buenos Aires, Argentina.
- Escuela de Bio y Nanotecnologías (EByN), Universidad Nacional de San Martín, San Martín (1650), Buenos Aires, Argentina.
Abstract
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.
MeSH
Vaccines, Covid-19 Vaccines, Antibodies, Antibodies, Neutralizing, Covid-19, Immunity