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

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.

Lorena M. Coria, Juan Manuel Rodriguez, Agostina Demaria, Laura A. Bruno, Mayra Rios Medrano, Celeste Pueblas Castro, Eliana F. Castro, Sabrina A. Del Priore, Andres C. Hernando Insúa, Ingrid G. Kaufmann, Lucas M. Saposnik, William B. Stone, Linael Prado, Ulises S. Notaro, Ayelen N. Amweg, Pablo U. Díaz, Martin Avra, Hugo Ortega, Ana Ceballos, Valeria Krum, Francisco M. Zurvar, Johanna E. Sidabra, Ignacio Drehé, Jonathan A. Baque, Mariana Li Causi, Analia V. De Nichilo, Cristian J. Payes, Teresa Southard, Julio C. Vega, Albert J. Auguste, Diego E. Álvarez, Juan M. Flo, Karina A. Pasquevich, Juliana Cassataro