Frontiers in Immunology (Feb 2022)

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

  • Lorena M. Coria,
  • Lucas M. Saposnik,
  • Celeste Pueblas Castro,
  • Eliana F. Castro,
  • Eliana F. Castro,
  • Laura A. Bruno,
  • William B. Stone,
  • Paula S. Pérez,
  • Maria Laura Darriba,
  • Lucia B. Chemes,
  • Julieta Alcain,
  • Ignacio Mazzitelli,
  • Augusto Varese,
  • Melina Salvatori,
  • Albert J. Auguste,
  • Albert J. Auguste,
  • Diego E. Álvarez,
  • Karina A. Pasquevich,
  • Juliana Cassataro

DOI
https://doi.org/10.3389/fimmu.2022.844837
Journal volume & issue
Vol. 13

Abstract

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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.

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