• Mijia Lu, Piyush Dravid, Yuexiu Zhang, Sheetal Trivedi, Anzhong Li, Olivia Harder, Mahesh Kc, Supranee Chaiwatpongsakorn, Ashley Zani, Adam Kenney, Cong Zeng, Chuanxi Cai, Chengjin Ye, Xueya Liang, Masako Shimamura, Shan-Lu Liu, Asuncion Mejias, Octavio Ramilo, Prosper N Boyaka, Jianming Qiu, Luis Martinez-Sobrido, Jacob S Yount, Mark E Peeples, Amit Kapoor, Stefan Niewiesk, and Jianrong Li.
• Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
• Proc. Natl. Acad. Sci. U.S.A. 2021 Mar 23; 118 (12).

AbstractThe current pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights an urgent need to develop a safe, efficacious, and durable vaccine. Using a measles virus (rMeV) vaccine strain as the backbone, we developed a series of recombinant attenuated vaccine candidates expressing various forms of the SARS-CoV-2 spike (S) protein and its receptor binding domain (RBD) and evaluated their efficacy in cotton rat, IFNAR-/-mice, IFNAR-/--hCD46 mice, and golden Syrian hamsters. We found that rMeV expressing stabilized prefusion S protein (rMeV-preS) was more potent in inducing SARS-CoV-2-specific neutralizing antibodies than rMeV expressing full-length S protein (rMeV-S), while the rMeVs expressing different lengths of RBD (rMeV-RBD) were the least potent. Animals immunized with rMeV-preS produced higher levels of neutralizing antibody than found in convalescent sera from COVID-19 patients and a strong Th1-biased T cell response. The rMeV-preS also provided complete protection of hamsters from challenge with SARS-CoV-2, preventing replication in lungs and nasal turbinates, body weight loss, cytokine storm, and lung pathology. These data demonstrate that rMeV-preS is a safe and highly efficacious vaccine candidate, supporting its further development as a SARS-CoV-2 vaccine.Copyright © 2021 the Author(s). Published by PNAS.

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