National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
Int J Mol Sci. 2022 Apr 28;23(9):4902. doi: 10.3390/ijms23094902.
During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 μg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 μg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.
在持续的 COVID-19 大流行期间，全球大规模接种疫苗以实现群体免疫，可以防止病毒进一步传播和变异。一种安全、有效、稳定、储存限制少且涉及可靠制造工艺的蛋白质亚单位疫苗将有利于在全球范围内分发。在这里，我们设计并生产了一种重组刺突（S）三聚体，该三聚体保持在预融合状态，具有高 ACE2 结合亲和力。啮齿动物接受了不同剂量的 S-三聚体（0.5、5 或 20 μg）抗原，与氢氧化铝（Alum）或乳液型佐剂（SWE）或无佐剂一起配制。两次接种后，评估了小鼠中的抗体反应、T 细胞反应以及滤泡辅助 T 细胞（Tfh）或生发中心（GC）B 细胞的数量；在叙利亚仓鼠感染模型上评估了保护效力。小鼠研究表明，用 SWE 佐剂化 S-三聚体可诱导出强大的体液免疫反应和 Th1 偏向的细胞免疫反应（低剂量），优于 Alum 诱导的反应。在叙利亚仓鼠研究中，当 S-三聚体用 SWE 佐剂化时，会诱导出针对原始谱系的活 SARS-CoV-2 和变体（Beta 或 Delta）的中和抗体水平升高，但其效力略有降低。此外，SWE 佐剂表现出剂量节省效应；因此，作为抗原的 S-三聚体的较低剂量（0.5 μg）可以诱导出相当的抗血清并提供完全免受病毒感染的保护。这些数据支持 SWE 作为佐剂增强 S-三聚体疫苗免疫原性的实用性，这对于进一步的临床测试是可行的。
