Details

Autor(en) / Beteiligte

• 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

Titel

Immunogenicity of SARS-CoV-2 Trimeric Spike Protein Associated to Poly(I:C) Plus Alum

Ist Teil von

• Frontiers in immunology, 2022-06, Vol.13, p.884760

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2022

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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 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.