| Autor: |
Andréa C. Oliveira, Ronaldo Da Silva Mohana Borges, Francisca H. Guedes-da-Silva, Thiago Moreno L. Souza, Andre M. Vale, Kamila Guimarães-Pinto, Daniel Paiva Barros de Abreu, Gustavo Guadagini Perez, Diogo Oliveira-Maciel, Herbert Leonel de Matos Guedes, Jesuino Rafael Machado Ferreira, Marcus V. M. Silva, Federico F. Marsili, Danielle A. S. Rodrigues, Alessandra Marcia da Fonseca-Martins, Orlando C. Ferreira, Alessandra D’Almeida Filardy, Luan Firmino-Cruz, Jerson L. Silva, Tulio M. Lima, Victor A. R. Pereira, Monique dos Santos Leandro, Andre M. O. Gomes, Renata G. F. Alvim, Bartira Rossi-Bergamnn, Amilcar Tanuri, Carlos H. Dumard, Júlio Souza dos-Santos, Luciana Conde, Ana Clara Vicente dos Santos |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
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-2in vitroby neutralization assay, after one or two boosts. 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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