Preclinical immunogenicity studies of a gamma variant-adapted recombinant vaccine formulation against COVID-19

DEMARÍA, AGOSTINA; RODRIGUEZ, JUAN MANUEL; LAURA BRUNO; MEDRANO, MAYRA RIOS; CASTRO, CELESTE PUEBLAS; CASTRO, ELIANA; DEL PRIORE, SABRINA A.; HERNANDO INSUA, ANDRÉS C.; KAUFMANN, INGRID G.; SAPOSNIK, LUCAS; 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.; ALVAREZ, DIEGO; FLO, JUAN M.; PASQUEVICH K; CASSATARO J; CORIA, LORENA

Barcelona, España

Congreso; World Vaccine Congress Europe 2023; 2023

The COVID-19 pandemic continues with the emergence of new variants of concern (VOC). One strategy to prevent breakthrough infections is developing safe and effective broad-spectrum vaccines. In this work, we present the preclinical studies of a RBD recombinant vaccine candidate derived from the Gamma SARS-CoV-2 variant adjuvanted with alum.BALB/c mice were immunized by intramuscular route with the vaccine formulation containing a variant adapted-RBD plus alum as adjuvant and then humoral and cellular immune responses were evaluated. The Gamma-adapted subunit vaccine elicited a long-lasting antibody response with cross-neutralizing activity against different variants of concern including the Omicron variant. Additionally, Gamma variant RBD-adapted vaccine elicited robust T cells responses with induction of Th1 and CD8+ T cell responses. To evaluate vaccine efficacy, an intranasal challenge with the virus in K18-hACE2 transgenic mice was performed after vaccination. We have shown that vaccine-induced immunity protected K18-hACE2 mice from intranasal challenge with SARS-CoV-2 increasing survival, reducing body weight loss and viral burden in the lungs and brain. Importantly, the subunit vaccine demonstrated a potent effect as heterologous booster of different vaccine platforms including the non-replicating adenovirus vaccine ChAdOx1-S, the mRNA vaccine BNT162b2 and the inactivated vaccine BBIBP-CorV, increasing cross-reactive antibody responses. Our study indicates that the adjuvanted Gamma RBD vaccine is highly immunogenic and a broad-spectrum vaccine candidate.