Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA; Center for Biodefense and Emerging Disease, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Vaccine. 2023 May 16;41(21):3337-3346. doi: 10.1016/j.vaccine.2023.04.006. Epub 2023 Apr 10.
Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have constituted a public health issue with drastic mortality higher than 34%, necessitating the development of an effective vaccine. During MERS-CoV infection, the trimeric spike protein on the viral envelope is primarily responsible for attachment to host cellular receptor, dipeptidyl peptidase 4 (DPP4). With the goal of generating a protein-based prophylactic, we designed a subunit vaccine comprising the recombinant S1 protein with a trimerization motif (S1-Fd) and examined its immunogenicity and protective immune responses in combination with various adjuvants. We found that sera from immunized wild-type and human DPP4 transgenic mice contained S1-specific antibodies that can neutralize MERS-CoV infection in susceptible cells. Vaccination with S1-Fd protein in combination with a saponin-based QS-21 adjuvant provided long-term humoral as well as cellular immunity in mice. Our findings highlight the significance of the trimeric S1 protein in the development of MERS-CoV vaccines and offer a suitable adjuvant, QS-21, to induce robust and prolonged memory T cell response.
中东呼吸综合征冠状病毒（MERS-CoV）的爆发已构成公共卫生问题，其死亡率高于 34%，因此需要开发有效的疫苗。在 MERS-CoV 感染过程中，病毒包膜上的三聚体刺突蛋白主要负责与宿主细胞受体二肽基肽酶 4（DPP4）结合。为了生成基于蛋白的预防性疫苗，我们设计了一种包含三聚化基序的重组 S1 蛋白的亚单位疫苗（S1-Fd），并结合各种佐剂研究了其免疫原性和保护性免疫应答。我们发现，免疫野生型和人 DPP4 转基因小鼠的血清中含有可中和易感细胞中 MERS-CoV 感染的 S1 特异性抗体。用 S1-Fd 蛋白联合皂素类 QS-21 佐剂进行免疫接种可在小鼠体内产生长期的体液和细胞免疫。我们的研究结果强调了三聚体 S1 蛋白在 MERS-CoV 疫苗开发中的重要性，并提供了一种合适的佐剂 QS-21，可诱导强烈而持久的记忆 T 细胞应答。
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