A Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection

CORIA, LORENA M.; RODRIGUEZ, JUAN MANUEL; DEMARIA, AGOSTINA; BRUNO, LAURA A.; MEDRANO, MAYRA RIOS; CASTRO, CELESTE PUEBLAS; CASTRO, ELIANA F.; DEL PRIORE, SABRINA A.; HERNANDO INSUA, ANDRES C.; KAUFMANN, INGRID G.; SAPOSNIK, LUCAS M.; STONE, WILLIAM B.; PRADO, LINEIA; NOTARO, ULISES S.; AMWEG, AYELEN N.; DIAZ, PABLO U.; AVARO, MARTIN; ORTEGA, HUGO; CEBALLOS, ANA; KRUM, VALERIA; ZURVARRA, FRANCISCO M.; SIDABRA, JOHANNA E.; DREHE, IGNACIO; BAQUÉ, JONATHAN A.; LI CAUSI, MARIANA; DE NICHILO, ANALIA V.; PAYES, CRISTIAN J.; SOUTHARD, TERESA; VEGA, JULIO C.; AUGUSTE, ALBERT J.; ÁLVAREZ, DIEGO E.; FLO, JUAN M.; PASQUEVICH, KARINA A.; CASSATARO, JULIANA

NATURE COMMUNICATIONS

Nature Research

Año: 2024 vol. 15 p. 1 - 14

2041-1723

In the context of continuous emergence of SARS-CoV-2 variants of concern (VOCs), one strategy to prevent the severe outcomes of COVID-19 is developing safe and effective broad-spectrum vaccines. Here, we present preclinical studies of a RBD vaccine derived from the Gamma SARS-CoV-2 variant adjuvanted with Alum. The Gamma-adapted RBD vaccine is more immunogenic than the Ancestral RBD vaccine in terms of inducing broader neutralizing antibodies. The Gamma RBD presents more immunogenic B-cell restricted epitopes and induces a higher proportion of specific-B cells and plasmablasts than the Ancestral RBD version. The Gamma-adapted vaccine induces antigen specific T cell immune responses and confers protection against Ancestral and Omicron BA.5 SARS-CoV-2 challenge in mice. Moreover, the Gamma RBD vaccine induces higher and broader neutralizing antibody activity than homologous booster vaccination in mice previously primed with different SARS-CoV-2 vaccine platforms. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.