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

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.

Silicon or Calcium Doping Coordinates the Immunostimulatory Effects of Aluminum Oxyhydroxide Nanoadjuvants in Prophylactic Vaccines

“…It induces enhanced antigen-specific humoral and cellular immunity in human papillomavirus (HPV), influenza A virus, and Hepatitis B virus (HBV) vaccines. − Alum-based combination adjuvants containing CpG ODN (TLR9 agonist), Poly­(I:C) (TLR3 agonist), SMIP7.10 (TLR7 agonist), and c-GAMP (STING agonist) have been demonstrated to boost balanced immune responses in influenza M2e peptide, HBV subunit, B. pertussis, and meningococcal polysaccharide vaccination models, respectively. − Additionally, composite aluminosilicate (AS) materials were constructed by modifying dendritic mesoporous silica nanoparticles (DMSNs) with VI Al–OH groups, which mediated cellular immunity in an OVA vaccination model . A Pickering emulsion using Alhydrogel as the squalene stabilizer was designed to enhance both humoral and cellular immunity in the SARS-CoV-2 RBD model .…”