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: SARS-CoV-2; adjuvants; alum; intradermal route; poly (I:C); spike protein; vaccine.
【저자키워드】 SARS-CoV-2, adjuvants, Spike protein, vaccine., Poly (I:C), alum, intradermal route, 【초록키워드】 IgG, Vaccine, vaccination, antibody, Cellular immune response, SARS-CoV-2 pandemic, Th1, lung, SARS-CoV-2 virus, in vitro, CD4, CD8, immunization, ELISA, B cell, Protein, serum, T cell, Bronchoalveolar lavage fluid, Neutralization assay, mice, RBD, IgA, adjuvant, BALF, IgG1, inactivated, Neutralizing titer, Combination, Lung inflammation, Vaccination strategy, germinal centers, poly(I:C, Subtypes, enzyme, domain, IgG2a, neutralizing titers, neutrophil recruitment, prefusion, positive, Th1 phenotype, trimeric, produced, addition, evaluated, required, reduced, supported, induce, producing, reduction in, expected, immunosorbent, New, IgG anti-spike antibody, the SARS-CoV-2, 【제목키워드】 immunogenicity, spike, poly(I:C,