Abstract
Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, Mastomys natalensis, which is widely spread in sub-Saharan Africa. LASV infection of humans can cause Lassa fever (LF), a disease associated with high morbidity and significant mortality. Recent evidence indicates an LASV expansion outside its traditional endemic areas. In 2017, the World Health Organization (WHO) included LASV in top-priority pathogens and released a Target Product Profile (TPP) for vaccine development. Likewise, in 2018, the US Food and Drug Administration added LF to a priority review voucher program to encourage the development of preventive and therapeutics measures. In this article, we review recent progress in LASV vaccine research and development with a focus on the impact of LASV genetic and biological diversity on the design and development of vaccine candidates meeting the WHO’s TPP for an LASV vaccine.
Highlights
Lassa virus (LASV) was originally isolated from a nurse (Lily Pinneo; strain LP) in 1969 during a nosocomial outbreak in a mission hospital in the city of Jos in north-central Nigeria[1,2]
Protection against Nigerian strains of LASV is a critical requirement for LASV vaccines[94]
World Health Organization (WHO) pre-qualification requirements raise a high bar for vaccine developers and emphasize the WHO-preferred vaccine candidate as a preventive and costeffective measure for the general population in endemic areas
Summary
Lassa virus (LASV) was originally isolated from a nurse (Lily Pinneo; strain LP) in 1969 during a nosocomial outbreak in a mission hospital in the city of Jos in north-central Nigeria[1,2]. The attenuated rVSV-N4CT1 vector was immunogenic in NHPs and induced only a mild inflammatory response after intra-thalamic inoculation[125] This vector was used to generate experimental vaccines expressing single or multiple GPs that protected NHPs against EBOV and MARV challenges[126,127,128], but there are no peer-reviewed pre-clinical data in support of the LASV vaccine based on the VesiculoVax platform. CEPI supported pre-clinical development of the LASV-GPC-based vaccine vectored by non-replicating simian adenovirus ChAdOx1129, but there is no evidence supporting the suitability of this platform to control LF on the basis of natural history of the disease and mechanisms of protective immunity[54,74,77,130]
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