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A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike.
Proc Natl Acad Sci U S A. 2021 03 23; 118(12)PN

Abstract

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.

Authors+Show Affiliations

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH 43210.Texas Biomedical Research Institute, San Antonio, TX 78227.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205. Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210. Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210. Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205. Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205. Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160.Texas Biomedical Research Institute, San Antonio, TX 78227.Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205. Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205. Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210; li.926@osu.edu. Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33688034

Citation

Lu, Mijia, et al. "A Safe and Highly Efficacious Measles Virus-based Vaccine Expressing SARS-CoV-2 Stabilized Prefusion Spike." Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 12, 2021.
Lu M, Dravid P, Zhang Y, et al. A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike. Proc Natl Acad Sci U S A. 2021;118(12).
Lu, M., Dravid, P., Zhang, Y., Trivedi, S., Li, A., Harder, O., Kc, M., Chaiwatpongsakorn, S., Zani, A., Kenney, A., Zeng, C., Cai, C., Ye, C., Liang, X., Shimamura, M., Liu, S. L., Mejias, A., Ramilo, O., Boyaka, P. N., ... Li, J. (2021). A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike. Proceedings of the National Academy of Sciences of the United States of America, 118(12). https://doi.org/10.1073/pnas.2026153118
Lu M, et al. A Safe and Highly Efficacious Measles Virus-based Vaccine Expressing SARS-CoV-2 Stabilized Prefusion Spike. Proc Natl Acad Sci U S A. 2021 03 23;118(12) PubMed PMID: 33688034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike. AU - Lu,Mijia, AU - Dravid,Piyush, AU - Zhang,Yuexiu, AU - Trivedi,Sheetal, AU - Li,Anzhong, AU - Harder,Olivia, AU - Kc,Mahesh, AU - Chaiwatpongsakorn,Supranee, AU - Zani,Ashley, AU - Kenney,Adam, AU - Zeng,Cong, AU - Cai,Chuanxi, AU - Ye,Chengjin, AU - Liang,Xueya, AU - Shimamura,Masako, AU - Liu,Shan-Lu, AU - Mejias,Asuncion, AU - Ramilo,Octavio, AU - Boyaka,Prosper N, AU - Qiu,Jianming, AU - Martinez-Sobrido,Luis, AU - Yount,Jacob S, AU - Peeples,Mark E, AU - Kapoor,Amit, AU - Niewiesk,Stefan, AU - Li,Jianrong, PY - 2021/3/10/entrez PY - 2021/3/11/pubmed PY - 2021/3/23/medline KW - SARS-CoV-2 vaccine KW - measles virus vector KW - prefusion spike JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 118 IS - 12 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/33688034/A_safe_and_highly_efficacious_measles_virus_based_vaccine_expressing_SARS_CoV_2_stabilized_prefusion_spike_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=33688034 DB - PRIME DP - Unbound Medicine ER -