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

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

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.