A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike

The 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...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 12; pp. 1 - 11
Main Authors:	Lu, Mijia, Dravid, Piyush, Zhang, Yuexiu, Trivedi, Sheetal, Li, Anzhong, Harder, Olivia, KC, Mahesh, Chaiwatpongsakorn, Supranee, Zani, Ashley, Kenney, Adam, Zeng, Cong, Cai, Chuanxi, Ye, Chengjin, Liang, Xueya, Shimamura, Masako, Liu, Shan-Lu, Mejias, Asuncion, Ramilo, Octavio, Boyaka, Prosper N., Qiu, Jianming, Martinez-Sobrido, Luis, Yount, Jacob S., Peeples, Mark E., Kapoor, Amit, Niewiesk, Stefan, Li, Jianrong
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 23-03-2021
Subjects:	Animals Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Biological Sciences COVID-19 - complications COVID-19 - pathology COVID-19 - prevention & control COVID-19 Vaccines - genetics COVID-19 Vaccines - immunology Cricetinae Disease Models, Animal Gene Expression Genetic Vectors - genetics Genetic Vectors - immunology Humans Immunization Immunogenicity, Vaccine Measles virus - genetics Measles virus - immunology Mice Mice, Transgenic Rats Spike Glycoprotein, Coronavirus - genetics Spike Glycoprotein, Coronavirus - immunology Vaccines, Synthetic - genetics Vaccines, Synthetic - immunology measles virus vector SARS-CoV-2 vaccine prefusion spike
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Summary:	The 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: M.L., P.D., Y.Z., S.T., A.L., O.H., X.L., M.E.P., A. Kapoor, S.N., and J.L. designed research; M.L., P.D., Y.Z., S.T., A.L., O.H., M.K.C., S.C., A.Z., A. Kenney, C.Z., C.C., C.Y., X.L., P.N.B., J.Q., L.M.-S., J.S.Y., M.E.P., A. Kapoor, S.N., and J.L. performed research; M.L., C.Y., M.S., S.-L.L., A.M., O.R., J.Q., L.M.-S., J.S.Y., M.E.P., A. Kapoor, S.N., and J.L. contributed new reagents/analytic tools; M.L., P.D., Y.Z., S.T., M.K.C., S.C., P.N.B., L.M.-S., M.E.P., A. Kapoor, S.N., and J.L. analyzed data; M.L. and J.L. wrote the paper; P.D., Y.Z., S.T., A.L., O.H., M.K.C., S.C., A.Z., A. Kenney, C.Z., C.Y., X.L., M.S., S.-L.L., A.M., O.R., P.N.B., J.Q., L.M.-S., J.S.Y., M.E.P., A. Kapoor, and S.N. edited the manuscript; and J.L. provided funding. 1P.D., Y.Z., S.T., A.L., O.H., and M.K.C. contributed equally to this work. Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved February 10, 2021 (received for review December 21, 2020)
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.2026153118