Inter-lineage variation of lassa virus glycoprotein epitopes: A challenge to lassa virus vaccine development
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AbstractLassa 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. Copyright 2020 by the author.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85082818931&doi=10.3390%2fv12040386&partnerID=40&md5=966261079e3ee8ecd23daab830e70215; http://hdl.handle.net/10713/12549
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Evaluation of Lassa virus vaccine immunogenicity in a CBA/J-ML29 mouse modelGoicochea, Marco Aurelio; Lukashevich, Igor S. (2011)Lassa virus (LASV) is widely spread in West Africa and can cause fatal Lassa fever. In addition to the significant public health problem in endemic regions there have been numerous imported cases to non-endemic countries. Due to limitations in treatment options and difficulties posed by reservoir control vaccination remains the most logical method of disease control; however we have no vaccine approved for human use. LASV is a pathogen that requires the highest level of biocontainment for study and as such vaccine development is both difficult and costly. ML29 is a reassortant virus containing the replication machinery of the nonpathogenic Mopeia virus and major immunogens of LASV. It displays an attenuated phenotype both in vitro and in vivo as compared to wild type LASV and therefore ML29 offers a safer immunogenic surrogate of LASV for vaccine research outside of BSL-4 facilities. We have established a small animal model for the evaluation of immunogenicity of LASV vaccine candidates based on unique phenotypic characteristics of ML29 in CBA/J mice. A single intraperitoneal immunization with the reassortant virus ML29 into CBA/J mice is non-pathogenic and sufficient to protect animals against a lethal homologous intracerebral challenge. Immunized mice display negligible levels of ML29-specific antibody titers, but LASV antigen-specific cell mediated immune (CMI) responses are detectable early and peak around day 8-10 after immunization. ML29 immune splenocytes display high numbers of IFN-? producing cells by ELISPOT and robust numbers of IFN-?+ and TNF-?+ CD4 and CD8 T lymphocytes by flow cytometry. In vivo CTL experiments show a correlation between Ag-specific cytotoxicity and the timing of protection induced by a single immunization with ML29. Furthermore, splenocyte transfers using donor cells from ML29 immunized mice display a similar kinetics of protection. Finally, mice that received splenocytes from ML29 immunized mice depleted of CD8+ cells all succumbed to a lethal challenge, further demonstrating the critical role of CD8 T cells in protection. This model has proven a useful immunological tool for the preliminary evaluation of immunogenicity and efficacy for other heterologous vaccine candidates against LASV outside of BSL-4 containment facilities necessitated by LASV.
Improving the breadth of the host's immune response to lassa virusZapata, J.C.; Medina-Moreno, S.; Guzmán-Cardozo, C. (MDPI AG, 2018)In 2017, the global Coalition for Epidemic Preparedness (CEPI) declared Lassa virus disease to be one of the world's foremost biothreats. In January 2018, World Health Organization experts met to address the Lassa biothreat. It was commonly recognized that the diversity of Lassa virus (LASV) isolated from West African patient samples was far greater than that of the Ebola isolates from the West African epidemic of 2013-2016. Thus, vaccines produced against Lassa virus disease face the added challenge that they must be broadly-protective against a wide variety of LASV. In this review, we discuss what is known about the immune response to Lassa infection. We also discuss the approaches used to make broadly-protective influenza vaccines and how they could be applied to developing broad vaccine coverage against LASV disease. Recent advances in AIDS research are also potentially applicable to the design of broadly-protective medical countermeasures against LASV disease. Copyright 2018 by the authors. Licensee MDPI, Basel, Switzerland.