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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Proc+Natl+Acad+Sci+U+S+A 2021 ; 118 (12): ä Nephropedia Template TP
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A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike #MMPMID33688034
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 SL; Mejias A; Ramilo O; Boyaka PN; Qiu J; Martinez-Sobrido L; Yount JS; Peeples ME; Kapoor A; Niewiesk S; Li J
Proc Natl Acad Sci U S A 2021[Mar]; 118 (12): ä PMID33688034show ga
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.