tetano
Editor, Senior Moderator
Front Immunol
. 2022 Feb 28;13:844837.
doi: 10.3389/fimmu.2022.844837. eCollection 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[SUP] 1 [/SUP], Lucas M Saposnik[SUP] 1 [/SUP], Celeste Pueblas Castro[SUP] 1 [/SUP], Eliana F Castro[SUP] 1 2 [/SUP], Laura A Bruno[SUP] 1 [/SUP], William B Stone[SUP] 3 [/SUP], Paula S Pérez[SUP] 4 [/SUP], Maria Laura Darriba[SUP] 1 [/SUP], Lucia B Chemes[SUP] 1 [/SUP], Julieta Alcain[SUP] 1 [/SUP], Ignacio Mazzitelli[SUP] 4 [/SUP], Augusto Varese[SUP] 4 [/SUP], Melina Salvatori[SUP] 4 [/SUP], Albert J Auguste[SUP] 3 5 [/SUP], Diego E Álvarez[SUP] 1 [/SUP], Karina A Pasquevich[SUP] 1 [/SUP], Juliana Cassataro[SUP] 1 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] 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.
Keywords: SARS- CoV-2; U-Omp19; adjuvant; germinal center cells; protease inhibitor.
. 2022 Feb 28;13:844837.
doi: 10.3389/fimmu.2022.844837. eCollection 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[SUP] 1 [/SUP], Lucas M Saposnik[SUP] 1 [/SUP], Celeste Pueblas Castro[SUP] 1 [/SUP], Eliana F Castro[SUP] 1 2 [/SUP], Laura A Bruno[SUP] 1 [/SUP], William B Stone[SUP] 3 [/SUP], Paula S Pérez[SUP] 4 [/SUP], Maria Laura Darriba[SUP] 1 [/SUP], Lucia B Chemes[SUP] 1 [/SUP], Julieta Alcain[SUP] 1 [/SUP], Ignacio Mazzitelli[SUP] 4 [/SUP], Augusto Varese[SUP] 4 [/SUP], Melina Salvatori[SUP] 4 [/SUP], Albert J Auguste[SUP] 3 5 [/SUP], Diego E Álvarez[SUP] 1 [/SUP], Karina A Pasquevich[SUP] 1 [/SUP], Juliana Cassataro[SUP] 1 [/SUP]
Affiliations
- PMID: 35296091
- PMCID: PMC8919065
- DOI: 10.3389/fimmu.2022.844837
Abstract
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[SUP]+[/SUP] 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.
Keywords: SARS- CoV-2; U-Omp19; adjuvant; germinal center cells; protease inhibitor.