A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region

Author:

Cai Yingyun1ORCID,Iwasaki Masaharu23,Motooka Daisuke4,Liu David X.1,Yu Shuiqing1ORCID,Cooper Kurt1,Hart Randy1,Adams Ricky1,Burdette Tracey1,Postnikova Elena N.1ORCID,Kurtz Jonathan1,St. Claire Marisa1ORCID,Ye Chengjin5,Kuhn Jens H.1ORCID,Martínez-Sobrido Luis5ORCID,de la Torre Juan Carlos2

Affiliation:

1. Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA

2. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA

3. Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

4. Laboratory of Pathogen Detection and Identification, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

5. Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA

Abstract

Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding intergenic region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

U.S. Department of Defense

MEXT | Japan Society for the Promotion of Science

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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