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.
Coria, L. M., Saposnik, L. M., Pueblas Castro, C., Castro, E. F., Bruno, L. A., Stone, W. B., Perez, P. S., Darriba, M. L., Chemes, L. B., Alcain, J., Mazzitelli, I., Varese, A., Salvatori, M., Auguste, A. J., Alvarez, D. E., Pasquevich, K. A. and Cassataro, J.
Instituto de Investigaciones Biotecnologicas Dr. Rodolfo A. Ugalde, Universidad Nacional de San Martin, Consejo Nacional de Investigaciones Cientificas y Tecnicas (UNSAM-CONICET), San Martin, Argentina.
Instituto de Virologia e Innovaciones Tecnologicas (IVIT), Centro de Investigaciones en Ciencias Veterinarias y Agronomicas (CICVyA), Instituto Nacional de Tecnologia Agropecuaria (INTA)-Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires, Argentina.
Department of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
Instituto de Investigaciones Biomedicas en Retrovirus y SIDA (INBIRS, Universidad de Buenos Aires-CONICET), Buenos Aires, Argentina.
Center for Emerging, Zoonotic, and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
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.
Frontiers in Immunology 13: 844837 (2022)