Recombinant spike protein vaccines coupled with adjuvants that have different modes of action induce protective immunity against SARS-CoV-2.
Recombinant spike protein vaccines coupled with adjuvants that have different modes of action induce protective immunity against SARS-CoV-2.
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DOI：
10.1016/j.vaccine.2023.08.054
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发表时间：
2023-08
期刊：
影响因子：
5.5
通讯作者：
S. Chiba;P. Halfmann;S. Iida;Yuichiro Hirata;Yuko Sato;M. Kuroda;T. Armbrust;Sam Spyra;Tadaki Suzuki;Y. Kawaoka
中科院分区：
文献类型：
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作者：
S. Chiba;P. Halfmann;S. Iida;Yuichiro Hirata;Yuko Sato;M. Kuroda;T. Armbrust;Sam Spyra;Tadaki Suzuki;Y. Kawaoka
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的刺突蛋白（S）是一种糖蛋白，表达于病毒粒子表面，通过直接与宿主受体相互作用介导宿主细胞的感染。因此，它是中和病毒感染性的合理靶标。在此，我们发现，以Alhydrogel或QS-21样佐剂Quil-A作为佐剂的重组S蛋白疫苗在叙利亚仓鼠模型中有效地诱导抗S受体结合结构域（RBD）血清IgG和中和抗体滴度，导致呼吸器官中显著低的SARS-CoV-2复制，并减少病毒攻击后的体重减轻。病毒攻击后的严重肺部炎症也被疫苗接种强烈抑制。我们还发现，用Alhydrogel、Quil-A或AS 03样佐剂化的S蛋白疫苗在小鼠中引起的中和抗体滴度显著高于无佐剂疫苗。尽管在用野生型S蛋白免疫的小鼠中，针对变异病毒B.1.351和B.1.617.2的中和抗体滴度显著下降，但针对变异S蛋白的结合抗体水平与针对野生型S蛋白的结合抗体水平相当。当来自免疫小鼠的脾细胞在体外用S蛋白再刺激时，诱导的Th 1或Th 2细胞因子水平在用野生型S或变体S再刺激后没有显著差异，表明针对变体的T细胞应答与针对野生型病毒的T细胞应答相同。在仓鼠中Omicron XBB-攻击后，用Alhydrogel或AS 03进行的野生型S-疫苗接种在第3天降低了肺病毒滴度，并且Quil-A佐剂化组显示出较少的体重减轻，尽管在体外几乎没有检测到针对XBB的血清中和抗体滴度。总的来说，与不同佐剂结合的重组疫苗可能是通过诱导各种免疫应答来对抗新变异病毒的有希望的模式。
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a glycoprotein, expressed on the virion surface, that mediates infection of host cells by directly interacting with host receptors. As such, it is a reasonable target to neutralize the infectivity of the virus. Here we found that a recombinant S protein vaccine adjuvanted with Alhydrogel or the QS-21-like adjuvant Quil-A effectively induced anti-S receptor binding domain (RBD) serum IgG and neutralizing antibody titers in the Syrian hamster model, resulting in significantly low SARS-CoV-2 replication in respiratory organs and reduced body weight loss upon virus challenge. Severe lung inflammation upon virus challenge was also strongly suppressed by vaccination. We also found that the S protein vaccine adjuvanted with Alhydrogel, Quil-A, or an AS03-like adjuvant elicited significantly higher neutralizing antibody titers in mice than did unadjuvanted vaccine. Although the neutralizing antibody titers against the variant viruses B.1.351 and B.1.617.2 declined markedly in mice immunized with wild-type S protein, the binding antibody levels against the variant S proteins were equivalent to those against wild-type S. When splenocytes from the immunized mice were re-stimulated with the S protein in vitro, the induced Th1 or Th2 cytokine levels were not significantly different upon re-stimulation with wild-type S or variant S, suggesting that the T-cell responses against the variants were the same as those against the wild-type virus. Upon Omicron XBB-challenge in hamsters, wild-type S-vaccination with Alhydrogel or AS03 reduced lung virus titers on Day 3, and the Quil-A adjuvanted group showed less body weight loss, although serum neutralizing antibody titers against XBB were barely detected in vitro. Collectively, recombinant vaccines coupled with different adjuvants may be promising modalities to combat new variant viruses by inducing various arms of the immune response.