Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate

Fernandez-Diaz, M.; Calderon, K.; Rojas-Neyra, A.; Vakharia, V. N.; Choque-Guevara, R.; Montalvan, A.; Poma-Acevedo, A.; Rios-Matos, D.; Agurto-Arteaga, A.; Cauti-Mendoza, M. D. G.; Perez-Martinez, N.; Isasi-Rivas, G.; Tataje-Lavanda, L.; Palomino, M.; Bailon, H.; Sernaque-Aguilar, Y.; Ygnacio-Aguire, F.; Criollo-Orozco, M.; Huaccachi-Gonzalez, E.; Delgado-Ccancce, E.; Villanueva-Perez, D.; Montesinos-Millan, R.; Gutierrez-Manchay, K.; Pauyac-Antezana, K.; Ramirez-Ortiz, I.; Quinones Garcia, M. S.; Cauna-Orocollo, Y.; Vallejos-Sanchez, K.; Rios-Angulo, A. A.; Nunez-Fernandez, D.; Salguedo-Boho

doi:10.1101/2021.03.07.434276

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bioRxiv · 10.1101/2021.03.07.434276

Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate

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Abstract

The COVID-19 pandemic has claimed the lives of millions of people worldwide and threatens to become an endemic problem, therefore the need for as many types of vaccines as possible is of high importance. Because of the millions of doses required, it is desirable that vaccines are not only safe and effective, but also easy to administer, store, and inexpensive to produce. Newcastle Disease Virus (NDV) is responsible for a respiratory disease in chickens. It has no pathogenic homologue in humans. NDV is recognized as an oncolytic virus, and its use in humans for oncological treatment is being evaluated. In the present work, we have developed two types of NDV-vectored candidate vaccines, which carry the surface-exposed RBD and S1 antigens of SARS-CoV-2, respectively. These vaccine candidates were produced in specific-pathogen-free embryonating chicken eggs, and purified from allantoic fluid before lyophilization. These vaccines were administered intranasally to three different animal models: mice, rats and hamsters, and evaluated for safety, toxicity, immunogenicity, stability and efficacy. Efficacy was evaluated in a challenge assay against active SARS-CoV-2 virus in the Golden Syrian hamster model. The NDV-vectored vaccine based on the S1 antigen was shown to be safe and highly immunogenic, with the ability to neutralize SARS-CoV-2 in-vitro, even with an extreme dilution of 1/640. Our results reveal that this vaccine candidate protects the lungs of the animals, preventing cellular damage in this tissue. In addition, this vaccine reduces the viral load in the lungs, suggesting that it may significantly reduce the likelihood of transmission. Being lyophilized, this vaccine candidate is very stable and can be stored for several months at 4-8C. In conclusion, our NDV-based vaccine candidate has shown a very favorable performance in the pre-clinical study, serving as evidence for a future evaluation in a Phase-I human clinical trial. This candidate represents a promising tool in the fight against COVID-19.

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Fernandez-Diaz, M., Calderon, K., Rojas-Neyra, A., Vakharia, V. N., Choque-Guevara, R., Montalvan, A., Poma-Acevedo, A., Rios-Matos, D., Agurto-Arteaga, A., Cauti-Mendoza, M. D. G., Perez-Martinez, N., Isasi-Rivas, G., Tataje-Lavanda, L., Palomino, M., Bailon, H., Sernaque-Aguilar, Y., Ygnacio-Aguire, F., Criollo-Orozco, M., Huaccachi-Gonzalez, E., Delgado-Ccancce, E., Villanueva-Perez, D., Montesinos-Millan, R., Gutierrez-Manchay, K., Pauyac-Antezana, K., Ramirez-Ortiz, I., Quinones Garcia, M. S., Cauna-Orocollo, Y., Vallejos-Sanchez, K., Rios-Angulo, A. A., Nunez-Fernandez, D., Salguedo-Boho. 2021-03-08. Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate. https://doi.org/10.1101/2021.03.07.434276

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