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

Abstract

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.

Effects of N-linked glycan of Lassa Virus Envelope Glycoprotein on the Immune Response

“…Most recently, the 10 th and 11 th glycans were reported to occlude the conformational GPC-B epitope located at the stalk of GPC (16). Notably, evidence from human survivor and vaccine development studies have shown that adaptive immune protection in LASV infection is probably conferred mainly by a cell-mediated immune response, especially for Type I IFN (9,(17)(18)(19)(20)(21)(22)(23). It was supposed that deletion of the glycan chain would expose the epitope and thus increase the immunogenicity of GPC.…”

Effects of N-Linked Glycan on Lassa Virus Envelope Glycoprotein Cleavage, Infectivity, and Immune Response

“…2017 ; Warner et al . 2018 ; Ibukun 2020 ). It was supposed that deletion of the glycan chain would expose the epitope and thus increase the immunogenicity of GPC.…”

The niche of One Health approaches in Lassa fever surveillance and control

“…Molecular epidemiology has so far revealed seven distinct lineages of the LASV, including four confirmed and three proposed lineages [ 20 – 24 ] suggesting localisation of infection around specific human-rodent communities and socioecology. Lineages I, II and III are found in Nigeria [ 22 ].…”

“…Lineages II and III are common in southern and north-central Nigeria respectively [ 22 ]. Lineage IV, which includes the Josiah strain, comprises the subclades IVa and IVb, predominant in the Mano River Union area (Sierra Leone, Liberia and Guinea) [ 20 ]. In Sierra Leone, LF is endemic in the Eastern Province, particularly Kenema District [ 24 ], but has been reported in almost all districts of the country.…”