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.

中文翻译：

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合成多抗原 MVA 疫苗 COH04S1 在叙利亚仓鼠和非人类灵长类动物中预防 SARS-CoV-2

第二代 COVID-19 疫苗可能有助于建立针对 SARS-CoV-2 及其新兴变体的保护性免疫。我们开发了 COH04S1，这是一种合成的多抗原改良痘苗安卡拉 SARS-CoV-2 疫苗，可共表达刺突和核衣壳抗原。在这里，我们报告了 COH04S1 疫苗在动物模型中的功效。我们证明，用 COH04S1 对叙利亚仓鼠进行肌肉或鼻内疫苗接种可诱导强大的 Th1 偏向抗原特异性体液免疫和交叉中和抗体 (NAb)，并防止鼻内 SARS-CoV-后体重减轻、下呼吸道感染和肺损伤。 2 挑战。此外，我们证明用 COH04S1 对非人类灵长类动物进行单剂或两剂疫苗接种会诱导强大的抗原特异性结合抗体、NAb 和偏向 Th1 的 T 细胞，在鼻内/气管内 SARS-CoV-2 攻击后可防止上呼吸道和下呼吸道感染，并引发有效的攻击后记忆性抗病毒反应。这些结果证明了通过不同的疫苗接种途径和剂量方案在动物模型中COH04S1介导的疫苗保护，补充了在临床试验中对这种多抗原SARS-CoV-2疫苗的持续研究。