Frontiers in Immunology (Jun 2022)
Immunogenicity of SARS-CoV-2 Trimeric Spike Protein Associated to Poly(I:C) Plus Alum
- Júlio Souza dos-Santos,
- Júlio Souza dos-Santos,
- Luan Firmino-Cruz,
- Luan Firmino-Cruz,
- Alessandra Marcia da Fonseca-Martins,
- Alessandra Marcia da Fonseca-Martins,
- Diogo Oliveira-Maciel,
- Diogo Oliveira-Maciel,
- Gustavo Guadagnini Perez,
- Gustavo Guadagnini Perez,
- Victor A. Roncaglia-Pereira,
- Victor A. Roncaglia-Pereira,
- Carlos H. Dumard,
- Carlos H. Dumard,
- Francisca H. Guedes-da-Silva,
- Francisca H. Guedes-da-Silva,
- Ana C. Vicente Santos,
- Ana C. Vicente Santos,
- Monique dos Santos Leandro,
- Jesuino Rafael Machado Ferreira,
- Kamila Guimarães-Pinto,
- Luciana Conde,
- Danielle A. S. Rodrigues,
- Marcus Vinicius de Mattos Silva,
- Renata G. F. Alvim,
- Tulio M. Lima,
- Federico F. Marsili,
- Daniel P. B. Abreu,
- Orlando C. Ferreira Jr.,
- Ronaldo da Silva Mohana Borges,
- Amilcar Tanuri,
- Amilcar Tanuri,
- Thiago Moreno L. Souza,
- Thiago Moreno L. Souza,
- Bartira Rossi-Bergmann,
- André M. Vale,
- Jerson Lima Silva,
- Jerson Lima Silva,
- Andréa Cheble de Oliveira,
- Andréa Cheble de Oliveira,
- Alessandra D’Almeida Filardy,
- Andre M. O. Gomes,
- Andre M. O. Gomes,
- Herbert Leonel de Matos Guedes,
- Herbert Leonel de Matos Guedes,
- Herbert Leonel de Matos Guedes
Affiliations
- Júlio Souza dos-Santos
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Júlio Souza dos-Santos
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Luan Firmino-Cruz
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Luan Firmino-Cruz
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Alessandra Marcia da Fonseca-Martins
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Alessandra Marcia da Fonseca-Martins
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Diogo Oliveira-Maciel
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Diogo Oliveira-Maciel
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Gustavo Guadagnini Perez
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Gustavo Guadagnini Perez
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Victor A. Roncaglia-Pereira
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Victor A. Roncaglia-Pereira
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Carlos H. Dumard
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Carlos H. Dumard
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Francisca H. Guedes-da-Silva
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Francisca H. Guedes-da-Silva
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Ana C. Vicente Santos
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Ana C. Vicente Santos
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Monique dos Santos Leandro
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Jesuino Rafael Machado Ferreira
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Kamila Guimarães-Pinto
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Luciana Conde
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Danielle A. S. Rodrigues
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Marcus Vinicius de Mattos Silva
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Renata G. F. Alvim
- Cell Culture Engineering Lab., Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Tulio M. Lima
- Cell Culture Engineering Lab., Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Federico F. Marsili
- Cell Culture Engineering Lab., Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Daniel P. B. Abreu
- Cell Culture Engineering Lab., Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Orlando C. Ferreira Jr.
- Institute of Biology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Ronaldo da Silva Mohana Borges
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Amilcar Tanuri
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Amilcar Tanuri
- Institute of Biology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Thiago Moreno L. Souza
- Immunopharmacology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
- Thiago Moreno L. Souza
- National Institute for Science and Technology on Innovation in Diseases of Neglected Populations (INCT/IDPN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
- Bartira Rossi-Bergmann
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- André M. Vale
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Jerson Lima Silva
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Jerson Lima Silva
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Andréa Cheble de Oliveira
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Andréa Cheble de Oliveira
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Alessandra D’Almeida Filardy
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Andre M. O. Gomes
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Andre M. O. Gomes
- National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Herbert Leonel de Matos Guedes
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Herbert Leonel de Matos Guedes
- Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Herbert Leonel de Matos Guedes
- Interdisciplinary Medical Research Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
- DOI
- https://doi.org/10.3389/fimmu.2022.884760
- Journal volume & issue
-
Vol. 13
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.
Keywords
