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

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+ 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.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) that developed into a global pandemic causing over 260 million cases and over 5.2 million deaths worldwide (Weekly epidemiological update, World Health Organization, WHO)
A monomeric version of receptor binding domain (RBD) preceded by SARS-CoV-2 spike signal peptide for secretion and a C-terminal hexahistidine (6xHis)-Tag was expressed after plasmid transfection in HEK-293 cells
Purified RBD was recognized by polyclonal antibodies in sera from a convalescent patient infected with SARS-CoV-2 (Figure 1B)

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) that developed into a global pandemic causing (as of November 30, 2021) over 260 million cases and over 5.2 million deaths worldwide (Weekly epidemiological update, World Health Organization, WHO). It is critical to find a way to optimize the existing vaccines to protect against the prevalent SARS-CoV-2 variants of concern (VOC) that are spreading globally [4]. Evidence of waning immunity and viral diversification creates a possible need for a booster vaccine dose to protect the population [5], leading advisory health agencies to recommend an additional dose of a COVID-19 vaccine. For all these reasons, there is a need to produce safer, more effective, highly scalable, and more affordable COVID-19 vaccines locally or regionally

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Results

Conclusion