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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.
  • Lu M; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Dravid P; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Zhang Y; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Trivedi S; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Li A; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Harder O; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Kc M; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Chaiwatpongsakorn S; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Zani A; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Kenney A; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Zeng C; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Cai C; Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Ye C; Texas Biomedical Research Institute, San Antonio, TX 78227.
  • Liang X; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Shimamura M; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Liu SL; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Mejias A; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Ramilo O; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Boyaka PN; Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.
  • Qiu J; Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.
  • Martinez-Sobrido L; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Yount JS; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Peeples ME; Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205.
  • Kapoor A; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Niewiesk S; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Li J; Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Article in English | MEDLINE | ID: covidwho-1125668
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, Synthetic / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / Genetic Vectors / COVID-19 / Measles virus Type of study: Experimental Studies Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, Synthetic / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / Genetic Vectors / COVID-19 / Measles virus Type of study: Experimental Studies Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Year: 2021 Document Type: Article