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A highly efficacious live attenuated mumps virus-based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike.
Zhang, Yuexiu; Lu, Mijia; Mahesh, K C; Kim, Eunsoo; Shamseldin, Mohamed M; Ye, Chengjin; Dravid, Piyush; Chamblee, Michelle; Park, Jun-Gyu; Hall, Jesse M; Trivedi, Sheetal; Chaiwatpongsakorn, Supranee; Kenny, Adam D; Murthy, Satyapramod Srinivasa; Sharma, Himanshu; Liang, Xueya; Yount, Jacob S; Kapoor, Amit; Martinez-Sobrido, Luis; Dubey, Purnima; Boyaka, Prosper N; Peeples, Mark E; Li, Jianrong.
  • Zhang Y; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Lu M; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Mahesh KC; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Kim E; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Shamseldin MM; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Ye C; Department of Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, TX 78227.
  • Dravid P; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Chamblee M; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Park JG; Department of Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, TX 78227.
  • Hall JM; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Trivedi S; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Chaiwatpongsakorn S; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Kenny AD; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Murthy SS; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Sharma H; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Liang X; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.
  • Yount JS; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Kapoor A; Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.
  • Martinez-Sobrido L; Center for Vaccines and Immunity, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH 43205.
  • Dubey P; Infectious Disease Institute, The Ohio State University, Columbus, OH 43210.
  • Boyaka PN; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • Peeples ME; Department of Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, TX 78227.
  • Li J; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH 43210.
Proc Natl Acad Sci U S A ; 119(33): e2201616119, 2022 08 16.
Article in English | MEDLINE | ID: covidwho-1960617
ABSTRACT
With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)-based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P-M or F-SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P-M gene junction was more efficient than from the F-SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1-/- mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Measles-Mumps-Rubella Vaccine / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Vaccine Efficacy Type of study: Observational study Topics: Vaccines / Variants Limits: Animals Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Measles-Mumps-Rubella Vaccine / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Vaccine Efficacy Type of study: Observational study Topics: Vaccines / Variants Limits: Animals Language: English Journal: Proc Natl Acad Sci U S A Year: 2022 Document Type: Article