Vaccine platforms to control Lassa fever

ABSTRACT

Introduction: 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.

Areas covered: 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.

KEYWORDS:

• Lassa virus
• Lassa fever
• vaccine research
• replication-competent vaccines

Declaration of interests

Research studies summarized in this paper were supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01RR13980, R01AI52367, R01AI068961 (to IS Lukashevich), R01AI093450 (to IS Lukashevich/P Pushko) and R43AI94700 (to P Pushko). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Medigen, Inc (Frederick, MD) has a license agreement with University of Maryland (Baltimore, MD) for clinical development of experimental vaccine ML29. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.