A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice

PUEBLAS CASTRO, CELESTE; STONE, WILLIAM B.; CHEMES, LUCIA B.; VARESE, AUGUSTO; ÁLVAREZ, DIEGO E.; CORIA, LORENA M.; CASTRO, ELIANA F.; PÉREZ, PAULA S.; ALCAIN, JULIETA; SALVATORI, MELINA; PASQUEVICH, KARINA A.; SAPOSNIK, LUCAS M.; BRUNO, LAURA A.; DARRIBA, MARIA LAURA; MAZZITELLI, IGNACIO; AUGUSTE, ALBERT J.; CASSATARO, JULIANA

Frontiers in Immunology

Frontiers Media S.A.

Año: 2022 vol. 13

In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8+ T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice.