A Lassa Fever Live-Attenuated Vaccine Based on Codon Deoptimization of the Viral Glycoprotein Gene
-
- Yingyun Cai
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Chengjin Ye
- Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA
-
- Benson Cheng
- Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA
-
- Aitor Nogales
- Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA
-
- Masaharu Iwasaki
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA
-
- Shuiqing Yu
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Kurt Cooper
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- David X. Liu
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Randy Hart
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Ricky Adams
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Tyler Brady
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Elena N. Postnikova
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Jonathan Kurtz
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Marisa St Claire
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Jens H. Kuhn
- Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
-
- Juan Carlos de la Torre
- Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA
-
- Luis Martínez-Sobrido
- Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA
-
- Peter Palese
- editor
説明
<jats:p>Lassa virus (LASV) infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever (LF) cases. Licensed LF vaccines are not available, and anti-LF therapy is limited to off-label use of the nucleoside analog ribavirin with uncertain efficacy. We describe the generation of a novel live-attenuated LASV vaccine candidate. This vaccine candidate is based on mutating wild-type (WT) LASV in a key region of the viral genome, the glycoprotein precursor (GPC) gene. These mutations do not change the encoded GPC but interfere with its production in host cells. This mutated LASV (rLASV-GPC/CD) behaves like WT LASV (rLASV-WT) in cell culture, but in contrast to rLASV-WT, does not cause disease in inoculated guinea pigs. Guinea pigs immunized with rLASV-GPC/CD were protected against an otherwise lethal exposure to WT LASV. Our results support the testing of this candidate vaccine in nonhuman primate models ofLF.</jats:p>
収録刊行物
-
- mBio
-
mBio 11 (1), 2020-02-25
American Society for Microbiology