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 - Mahesh, K. C.
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
N1 - Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/3/23
Y1 - 2021/3/23
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.
AB - 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.
KW - SARS-CoV-2 vaccine | measles virus vector | prefusion spike
UR - http://www.scopus.com/inward/record.url?scp=85102711382&partnerID=8YFLogxK
U2 - 10.1073/pnas.2026153118
DO - 10.1073/pnas.2026153118
M3 - Article
C2 - 33688034
AN - SCOPUS:85102711382
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
M1 - e2026153118
ER -