title: Vaccine platforms to control Lassa fever.
abstract: Lassa virus (LASV), the most prominent human pathogen of the Arenaviridae, is transmitted to humans from infected rodents and can cause Lassa Fever (LF). The sizeable disease burden in West Africa, numerous imported LF cases worldwide, and the possibility that LASV can be used as an agent of biological warfare make a strong case for vaccine development. There are no licensed LASV vaccines and the antiviral treatment is limited to an off-label use of ribavirin that is only partially effective.
  
  
  
  LASV vaccine development is hampered by high cost of biocontainment requirement, the absence of appropriate small animal models, genetic diversity of LASV species, and by high HIV-1 prevalence in LASV endemic areas. Over the past 15 years several vaccine platforms have been developed. Natural history of LASV and pathogenesis of the disease provide strong justification for replication-competent (RC) vaccine as one of the most feasible approaches to control LF. Development of LASV vaccine candidates based on reassortant, recombinant, and alphavirus replicon technologies is covered in this review. Expert commentary: Two lead RC vaccine candidates, reassortant ML29 and recombinant VSV/LASV, have been successfully tested in non-human primates and have been recommended by international vaccine experts for rapid clinical development. Both platforms have powerful molecular tools to further secure safety, improve immunogenicity, and cross-protection. These platforms are well positioned to design multivalent vaccines to protect against all LASV strains citculatrd in West Africa. The regulatory pathway of Candid #1, the first live-attenuated arenaviral vaccine against Argentine hemorrhagic, will be a reasonable guideline for LASV vaccine efficacy trials.
authors.affiliation: a Department of Pharmacology and Toxicology, School of Medicine, and the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases , University of Louisville , Louisville , KY , USA.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
authors.affiliation: b Medigen, Inc ., Frederick , MD , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pushko
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000639:trends; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007835:Lassa Fever / Q000276:immunology / Q000517:prevention & control*; D007836:Lassa virus / Q000276:immunology*; D011323:Primates; D014613:Vaccines, Attenuated / Q000276:immunology / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000276:immunology / Q000302:isolation & purification; D014765:Viral Vaccines / Q000276:immunology* / Q000302:isolation & purification*
chemical_list: D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: Lassa fever; Lassa virus; replication-competent vaccines; vaccine research