Common Antiviral Cytotoxic T-Lymphocyte Epitope for Diverse Arenaviruses

Oldstone, Michael B. A.; Lewicki, Hanna; Homann, Dirk; Nguyen, Christophe; Julien, Sylvianne; Gairin, Jean Edouard

doi:10.1128/jvi.75.14.6273-6278.2001

Cited by 18 publications

(20 citation statements)

References 32 publications

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“…10,14,15,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] Studies of convalescent sera from patients with Lassa Fever or human HLA transgenic mice identified a number of epitope targets within the NP, GP1, GP2 and GS proteins. 11,12,16,19,[57][58][59][60][61][62][63] Recent work in a guinea pig model utilizing the GP1 and GP2 proteins in a DNA vaccine resulted in adequate protection from challenge virus. [13][14][15][16]20 Our review of Lassa vaccine development efforts did not show that the Lassa L protein has ever been used as part of the antigens in a subunit vaccine, although the L protein was shown to be protective in animal studies of other arenavirus like lymphocytic choriomeningitis virus.…”

Section: Discussionmentioning

confidence: 99%

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

Leblanc

Moise

Luza

et al. 2014

Human Vaccines & Immunotherapeutics

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Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-g CD4C T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models.

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Section: Discussionmentioning

confidence: 99%

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

Leblanc

Moise

Luza

et al. 2014

Human Vaccines & Immunotherapeutics

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“…The LCMV NP 118-126 epitope shares 78% homology with LASV and MOPV NP and constituted more than 97% of the total bulk CTL produced in BALB mice. The 118-126 aa peptides derived from the NP of LCMV, LASV and MOPV bound at high affinity to L d [155].…”

Section: Lasv Np Expressed In Vaccinia Virusmentioning

confidence: 99%

Lassa Virus Genome

Igor¹,

Sica²

2006

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Lassa virus (LASV), the most dangerous human pathogen among the Arenaviridae, belongs to a complex of genetically related virus strains responsible for the deaths of thousands of people in West Africa each year. The virus has a bi-segmented (L and S) single-stranded RNA genome. Each segment contains two genes in ambisense orientation. The L RNA encodes a large protein, L, or RdRp and a small zinc-binding, Z protein. The S RNA encodes the major structural proteins, nucleoprotein (NP) and glycoprotein precursor (GPC), cleaved into signal peptide, GP1, and GP2 glycoproteins. Genetic diversity among LASV strains is the highest within the family Arenaviridae and NP and RdRp genes are the most variable among LASV genes. The LASV genetic diversity is a great challenge for vaccine development.In addition to LASV and the prototype lymphocytic choriomeningitis virus (LCMV), the Old World group of arenaviruses includes three other related viruses, Mopeia (MOPV), Mobala (MOBV), and Ippy (IPPYV). These viruses as well as a MOP/LAS reassortant carrying the L RNA segment from MOPV and S RNA segment from LASV are non-pathogenic for experimental animals and are able to induce protective immunity against LASV. Lassa Fever pathogenesis is a sum of the effects induced by viral replication and immune response. The goal of this review is to cover recent publications on viral and host genes that control LASV virulence. The full-length genome sequence of LASV isolates and LASV-related nonpathogenic arenaviruses will provide a useful genetic tool to map LASV genes involved in virulence and to gain insight into phylogeny and evolution of the Old World arenaviruses.

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“…ter Meulen et al have already identified LASVspecific CD4 ϩ T-cell epitopes that are conserved with other arenavirus family members (40). Similarly, in murine models, cross-reactive CD8 ϩ T-cell epitopes have been identified among several arenaviruses, including LASV, LCMV, and Pichinde virus (24,28) While our approach to epitope identification in this study was tailored specifically for LASV, it represents a model system that could be applied to any virus (or other intracellular pathogen). The minimum requirements needed to utilize this approach are (i) existing sequence data for the pathogen in question, (ii) access to the genome (DNA or RNA) of the pathogen for the purpose of generating rVV vectors, (iii) HLA transgenic mice, and (iv) access to BSL-2 facilities for in vitro and in vivo studies.…”

Section: Fig 7 Functional Avidity Of Cd8mentioning

confidence: 99%

Identification of Protective Lassa Virus Epitopes That Are Restricted by HLA-A2

Botten

Alexander²,

Pasquetto

et al. 2006

J Virol

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Recovery from Lassa virus (LASV) infection usually precedes the appearance of neutralizing antibodies, indicating that cellular immunity plays a primary role in viral clearance. To date, the role of LASV-specific CD8 ؉ T cells has not been evaluated in humans. To facilitate such studies, we utilized a predictive algorithm to identify candidate HLA-A2 supertype epitopes from the LASV nucleoprotein and glycoprotein precursor (GPC) genes. We identified three peptides (GPC 42-50 , GLVGLVTFL; GPC 60-68 , SLYKGVYEL; and GPC 441-449 , YLISIFLHL) that displayed high-affinity binding (<98 nM) to HLA-A*0201, induced CD8؉ T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LASV GPC in human HLA-A*0201-positive target cells. HLA-A*0201 mice immunized with either GPC 42-50 or GPC 60-68 were protected against challenge with a recombinant vaccinia virus that expressed LASV GPC. The epitopes identified in this study represent potential diagnostic reagents and candidates for inclusion in epitope-based vaccine constructs. Our approach is applicable to any pathogen with existing sequence data, does not require manipulation of the actual pathogen or access to immune human donors, and should therefore be generally applicable to category A through C agents and other emerging pathogens.

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Common Antiviral Cytotoxic T-Lymphocyte Epitope for Diverse Arenaviruses

Abstract: Members of the

Cited by 18 publications

References 32 publications

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

Lassa Virus Genome

Identification of Protective Lassa Virus Epitopes That Are Restricted by HLA-A2

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