Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Front Immunol. 2022 Jun 30;13:884760. doi: 10.3389/fimmu.2022.884760. eCollection 2022.
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 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.
SARS-CoV-2 大流行对全球造成了社会和经济影响，而疫苗接种是减轻这些损害的有效策略。对于高疫苗需求，需要新的佐剂制剂，特别是诱导 Th1 表型的佐剂制剂。在此，我们通过皮内（ID）途径评估了一种使用 Alum 和聚肌苷酸：聚胞苷酸[Poly（I：C）]佐剂与 SARS-CoV-2 刺突蛋白三聚体融合前构象组合的疫苗接种策略。我们通过酶联免疫吸附测定（ELISA）发现，在两次或三次免疫后，血清中的 IgG 抗刺突抗体水平很高，通过中和测定发现对 SARS-CoV-2 的中和效价很高。通过评估 IgG 亚型的产生，如预期的那样，我们发现含有 Poly（I：C）的制剂诱导 IgG2a，而 Alum 则没有。这两种佐剂的组合诱导了高水平的 IgG1 和 IgG2a。此外，产生干扰素-γ的 CD4 和 CD8 T 细胞的细胞免疫反应相当，表明 Alum + Poly（I：C）组合支持 Th1 表型。基于高中和效价，我们评估了针对受体结合域（RBD）和刺突的生发中心中的 B 细胞，并观察到在 Alum + Poly（I：C）组合作用下诱导了更多的阳性 B 细胞。此外，这些 B 细胞产生针对 RBD 和非 RBD 部位的抗体。我们还研究了这种疫苗制备[带有 Alum + Poly（I：C）的刺突蛋白]在感染失活 SARS-CoV-2 病毒的小鼠肺部中的作用。我们发现 IgG 的产生，但 IgA 没有，并且在小鼠的支气管肺泡灌洗液（BALF）中中性粒细胞募集减少，这表明我们的免疫方案减轻了肺部炎症。总而言之，我们的数据表明，Alum 和 Poly（I：C）联合使用可能是通过皮内途径对抗 SARS-CoV-2 的疫苗的佐剂组合。
