A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region
Yíngyún Caì, Masaharu Iwasaki, Daisuke Motooka, David X. Liu, Shuǐqìng Yú, Kurt Cooper, Randy Hart, Ricky Adams, Tracey Burdette, Elena Postnikova, Jonathan Kurtz, Marisa St. Claire, Chengjin Ye, Jens H. Kuhn, Luis Martínez‐Sobrido, Juan Carlos de la Torre
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.