AUTHOR=dos-Santos Júlio Souza , Firmino-Cruz Luan , da Fonseca-Martins Alessandra Marcia , Oliveira-Maciel Diogo , Perez Gustavo Guadagnini , Roncaglia-Pereira Victor A. , Dumard Carlos H. , Guedes-da-Silva Francisca H. , Santos Ana C. Vicente , Leandro Monique dos Santos , Ferreira Jesuino Rafael Machado , Guimarães-Pinto Kamila , Conde Luciana , Rodrigues Danielle A. S. , Silva Marcus Vinicius de Mattos , Alvim Renata G. F. , Lima Tulio M. , Marsili Federico F. , Abreu Daniel P. B. , Ferreira Jr. Orlando C. , Mohana Borges Ronaldo da Silva , Tanuri Amilcar , Souza Thiago Moreno L. , Rossi-Bergmann Bartira , Vale André M. , Silva Jerson Lima , de Oliveira Andréa Cheble , Filardy Alessandra D’Almeida , Gomes Andre M. O. , de Matos Guedes Herbert Leonel TITLE=Immunogenicity of SARS-CoV-2 Trimeric Spike Protein Associated to Poly(I:C) Plus Alum JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.884760 DOI=10.3389/fimmu.2022.884760 ISSN=1664-3224 ABSTRACT=

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid [Poly(I:C)] adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after two or three immunizations. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation [spike protein with Alum + Poly(I:C)] in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.