RT Journal Article
SR Electronic
T1 Immunogenicity of SARS-CoV-2 trimetric spike protein associated to Poly(I:C) plus Alum
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.05.461434
DO 10.1101/2021.10.05.461434
A1 Júlio Souza dos-Santos
A1 Luan Firmino-Cruz
A1 Alessandra Marcia da Fonseca-Martins
A1 Diogo Oliveira-Maciel
A1 Gustavo Guadagini Perez
A1 Victor A. R. Pereira
A1 Carlos H. Dumard
A1 Francisca H. Guedes-da-Silva
A1 Ana C. Vicente Santos
A1 Monique dos Santos Leandro
A1 Jesuino Rafael Machado Ferreira
A1 Kamila Guimarães-Pinto
A1 Luciana Conde
A1 Danielle A. S. Rodrigues
A1 Marcus Vinicius de Mattos Silva
A1 Renata G. F. Alvim
A1 Tulio M. Lima
A1 Federico F. Marsili
A1 Daniel P. B. Abreu
A1 Orlando Ferreira
A1 Ronaldo da Silva Mohana Borges
A1 Amilcar Tanuri
A1 Thiago Moreno L. Souza
A1 Bartira Rossi-Bergamnn
A1 André M. Vale
A1 Jerson Lima Silva
A1 Andrea Cheble de Oliveira
A1 Alessandra D’Almeida Filardy
A1 Andre M. O. Gomes
A1 Herbert Leonel de Matos Guedes
YR 2021
UL http://biorxiv.org/content/early/2021/10/11/2021.10.05.461434.abstract
AB 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 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.Competing Interest StatementThe authors have declared no competing interest.