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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

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. prot...

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Autores principales: Coria, Lorena M., Saposnik, Lucas M., Pueblas Castro, Celeste, Castro, Eliana Florencia, Bruno, Laura A., Stone, William B., Pérez, Paula S., Darriba, Maria Laura, Chemes, Lucia B., Alcain, Julieta, Mazzitelli, Ignacio, Varese, Augusto, Salvatori, Melina, Auguste, Albert J., Álvarez, Diego E., Pasquevich, Karina A., Cassataro, Juliana
Formato: info:ar-repo/semantics/artículo
Lenguaje:Inglés
Publicado: Frontiers Media 2024
Materias:
Vaccine Adjuvants
Proteinase Inhibitors
Severe Acute Respiratory Syndrome Coronavirus 2
Antibodies
Mice
Coadyuvantes de Vacunas
Inhibidores de Proteinasas
Coronavirus del Síndrome Respiratorio Agudo Grave 2
Anticuerpos
Ratón
Germinal Center Cells
Células del Centro Germinal
Acceso en línea:http://hdl.handle.net/20.500.12123/16609
https://www.frontiersin.org/articles/10.3389/fimmu.2022.844837/full
https://doi.org/10.3389/fimmu.2022.844837
Sumario: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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