Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile.
Sección Virus Oncogénicos y Sub-Departamento Enfermedades Virales, Instituto de Salud Pública de Chile, Ñuñoa, Chile.
Vaccine. 2024 Oct 3;42(23):126203. doi: 10.1016/j.vaccine.2024.126203. Epub 2024 Aug 22.
SARS-CoV-2 is the causative virus of COVID-19, which has been responsible for millions of deaths worldwide since its discovery. After its emergence, several variants have been identified that challenge the efficacy of the available vaccines. Previously, we generated and evaluated a vaccine based on a recombinant Bacillus Calmette-Guérin (rBCG) expressing the nucleoprotein (N) of SARS-CoV-2 (rBCG-N-SARS-CoV-2). This protein is a highly immunogenic antigen and well conserved among variants. Here, we tested the administration of this vaccine with recombinant N and viral Spike proteins (S), or Receptor Binding Domain (RBD-Omicron variant), plus a booster with the recombinant proteins only, as a novel and effective strategy to protect against SARS-CoV-2 variants.
BALB/c mice were immunized with rBCG-N-SARS-CoV-2 and recombinant SARS-CoV-2 proteins in Alum adjuvant, followed by a booster with recombinant proteins to assess the safety and virus-specific cellular and humoral immune responses against SARS-CoV-2 antigens.
Immunization with rBCG-N-SARS-CoV-2 + recombinant proteins as a vaccine was safe and promoted the activation of CD4 and CD8 T cells that recognize SARS-CoV-2 N, S, and RBD antigens. These cells were able to secrete cytokines with an antiviral profile. This immunization strategy also induced robust titers of specific antibodies against N, S, and RBD and neutralizing antibodies of SARS-CoV-2.
Co-administration of the rBCG-N-SARS-CoV-2 vaccine with recombinant SARS-CoV-2 proteins could be an effective alternative to control particular SARS-CoV-2 variants. Due to its safety and capacity to induce virus-specific immune responses, we believe the rBCG-N-SARS-CoV-2 + Proteins vaccine could be an attractive candidate to protect against this virus, especially in newborns.
SARS-CoV-2 是 COVID-19 的致病病毒，自发现以来，它已在全球造成数百万人死亡。出现后，已鉴定出几种挑战现有疫苗效力的变体。此前，我们生成并评估了一种基于表达 SARS-CoV-2 核蛋白（N）的重组卡介苗（rBCG）的疫苗（rBCG-N-SARS-CoV-2）。该蛋白是一种高度免疫原性抗原，在变体中高度保守。在这里，我们测试了用重组 N 和病毒 Spike 蛋白（S），或受体结合域（Omicron 变体），加上重组蛋白的加强针来管理这种疫苗，作为一种新的有效的策略来预防 SARS-CoV-2 变体。
BALB/c 小鼠用 rBCG-N-SARS-CoV-2 和重组 SARS-CoV-2 蛋白在 Alum 佐剂中免疫，然后用重组蛋白进行加强针，以评估针对 SARS-CoV-2 抗原的安全性和病毒特异性细胞和体液免疫反应。
rBCG-N-SARS-CoV-2 + 重组蛋白作为疫苗免疫是安全的，并促进了识别 SARS-CoV-2 N、S 和 RBD 抗原的 CD4 和 CD8 T 细胞的激活。这些细胞能够分泌具有抗病毒谱的细胞因子。这种免疫策略还诱导了针对 N、S 和 RBD 的特异性抗体和 SARS-CoV-2 的中和抗体的高滴度。
rBCG-N-SARS-CoV-2 疫苗与重组 SARS-CoV-2 蛋白联合使用可能是控制特定 SARS-CoV-2 变体的有效替代方法。由于其安全性和诱导病毒特异性免疫反应的能力，我们相信 rBCG-N-SARS-CoV-2 + 蛋白疫苗可能是保护这种病毒的有吸引力的候选者，特别是在新生儿中。
