Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

Chiuppesi, F.; Nguyen, V. H.; 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, M. G.; Shostak, Y.; Wussow, F.; Diamond, D. J.

doi:10.1101/2021.09.15.460487

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bioRxiv · 10.1101/2021.09.15.460487

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

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Abstract

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.

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Chiuppesi, F., Nguyen, V. H., 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, M. G., Shostak, Y., Wussow, F., Diamond, D. J.. 2021-09-15. Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates. https://doi.org/10.1101/2021.09.15.460487

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