Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates.
Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates.
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DOI：
10.1038/s41541-022-00436-6
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发表时间：
2022-01-21
期刊：
影响因子：
9.2
通讯作者：
Diamond DJ
中科院分区：
文献类型：
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作者：
Chiuppesi F;Nguyen VH;Park Y;Contreras H;Karpinski V;Faircloth K;Nguyen J;Kha M;Johnson D;Martinez J;Iniguez A;Zhou Q;Kaltcheva T;Frankel P;Kar S;Sharma A;Andersen H;Lewis MG;Shostak Y;Wussow F;Diamond DJ
第二代COVID-19疫苗可能有助于建立针对SARS-CoV-2及其新变体的保护性免疫。我们开发了COH04S1，这是一种合成的多抗原修饰的基于安卡拉痘苗的SARS-CoV-2疫苗，它共同表达刺突抗原和核衣壳抗原。在这里，我们报告了COH04S1疫苗在动物模型中的有效性。我们证明，叙利亚仓鼠肌内或鼻内接种COH04S1可诱导强大的th1偏倚抗原特异性体液免疫和交叉中和抗体（NAb），并在鼻内SARS-CoV-2攻击后防止体重减轻、下呼吸道感染和肺损伤。此外，我们证明，单剂或双剂COH04S1非人类灵长类动物疫苗可诱导强效抗原特异性结合抗体、NAb和th1偏好T细胞，在鼻内/气管内SARS-CoV-2攻击后保护上呼吸道和下呼吸道感染，并触发强效的攻击后遗忘性抗病毒反应。这些结果表明，通过不同的接种途径和剂量方案，coh04s1介导的疫苗在动物模型中具有保护作用，补充了正在进行的临床试验中对这种多抗原SARS-CoV-2疫苗的研究。
Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.