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IMMUNOGENICITY OF SARS-COV-2 TRIMERIC SPIKE PROTEIN ASSOCIATED TO POLY(I:C) PLUS ALUM
Adjuvantes
Via intradérmica
Vaccine
Ácido policitidílico
SARS-CoV-2
Alúmen
Author
Affilliation
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 in Portuguese
Proteína de picoAdjuvantes
Via intradérmica
Vaccine
Ácido policitidílico
SARS-CoV-2
Alúmen
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