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Inter-Lineage Variation of Lassa Virus Glycoprotein Epitopes: A Challenge to Lassa Virus Vaccine Development

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Viruses 2020, 12(4), 386; https://doi.org/10.3390/v12040386
Received: 22 February 2020 / Revised: 26 March 2020 / Accepted: 30 March 2020 / Published: 31 March 2020
(This article belongs to the Special Issue Arenaviruses 2020)
Lassa virus (LASV), which causes considerable morbidity and mortality annually, has a high genetic diversity across West Africa. LASV glycoprotein (GP) expresses this diversity, but most LASV vaccine candidates utilize only the Lineage IV LASV Josiah strain GP antigen as an immunogen and homologous challenge with Lineage IV LASV. In addition to the sequence variation amongst the LASV lineages, these lineages are also distinguished in their presentations. Inter-lineage variations within previously mapped B-cell and T-cell LASV GP epitopes and the breadth of protection in LASV vaccine/challenge studies were examined critically. Multiple alignments of the GP primary sequence of strains from each LASV lineage showed that LASV GP has diverging degrees of amino acid conservation within known epitopes among LASV lineages. Conformational B-cell epitopes spanning different sites in GP subunits were less impacted by LASV diversity. LASV GP diversity should influence the approach used for LASV vaccine design. Expression of LASV GP on viral vectors, especially in its prefusion configuration, has shown potential for protective LASV vaccines that can overcome LASV diversity. Advanced vaccine candidates should demonstrate efficacy against all LASV lineages for evidence of a pan-LASV vaccine. View Full-Text
Keywords: lassa virus; lassa virus diversity; glycoprotein; epitopes; lassa virus vaccine lassa virus; lassa virus diversity; glycoprotein; epitopes; lassa virus vaccine
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Ibukun, F.I. Inter-Lineage Variation of Lassa Virus Glycoprotein Epitopes: A Challenge to Lassa Virus Vaccine Development. Viruses 2020, 12, 386.

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