Epitope polarity and adjuvants influence the fine specificity of the humoral response against Semliki Forest virus specific peptide vaccines

Fernandez, I; Harmsen, M.; Benaissa-Trouw, Barry J.; Stuij, I.; Puyk, W. C.; Meloen, Rob H.; Snippe, H.; Kraaijeveld, C. A.

doi:10.1016/s0264-410x(98)00038-3

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…6). This covers a protective B-cell epitope, residues 240 -246, in SFV protein E2 (71). It also covers part of a protective epitope, residues 227-243, found by Grosfeld et al (48).…”

Section: Discussionmentioning

confidence: 62%

“…Some of these fall in or are close to regions earlier reported to be of functional interest. Thus, the antibody mabE2v 142-146 epitope subsists in a variable, in the native virus-hidden, sequence region of the E2 glycoprotein reported as a T helper cell epitope (71). A potential receptor-binding domain is targeted by mabE2r [211][212][213][214][215][216][217][218] .…”

Section: Discussionmentioning

confidence: 99%

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Prefusion Rearrangements Resulting in Fusion Peptide Exposure in Semliki Forest Virus

Hammar¹,

Markarian²,

Haag³

et al. 2003

Journal of Biological Chemistry

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Semliki Forest virus (SFV), like many enveloped viruses, takes advantage of the low pH in the endosome to convert into a fusion-competent configuration and complete infection by fusion with the endosomal membrane. Unlike influenza virus, carrying an N-terminal fusion peptide, SFV represents a less-well understood fusion principle involving an endosequence fusion peptide. To explore the series of events leading to a fusogenic configuration of the SFV, we exposed the virus to successive acidification, mimicking endosomal conditions, and followed structural rearrangements at probed sensor surfaces. Thus revealed, the initial phase involves a transient appearance of a non-linear neutralizing antibody epitope in the fusion protein, E1. Concurrent with the disappearance of this epitope, a set of masked sequences in proteins E1 and E2 became exposed. When pH reached 6.0 -5.9 the virion transformed into a configuration of enlarged diameter with the fusion peptide optimally exposed. Simultaneously, a partly hidden sequence close to the receptor binding site in E2 became fully uncovered. At this presumably fusogenic stage, maximally 80 fusion peptide-identifying antibody Fab fragments could be bound per virion, i.e. one ligand per three copies of the fusion protein. The phenomena observed are discussed in terms of alphavirus structure and reported functional domains.

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“…6). This covers a protective B-cell epitope, residues 240 -246, in SFV protein E2 (71). It also covers part of a protective epitope, residues 227-243, found by Grosfeld et al (48).…”

Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Prefusion Rearrangements Resulting in Fusion Peptide Exposure in Semliki Forest Virus

Hammar¹,

Markarian²,

Haag³

et al. 2003

Journal of Biological Chemistry

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“…Six promiscuous peptide sequences selected for binding to purified DRB1‫ء‬ molecules were chosen to design 34-mer Cys-T-B-Cys LPCs. Based on our evaluation of published results concerning the immunogenicity induced with linear peptides containing T-and B-cell epitopes, a polarity of T-B was chosen (16)(17)(18)55). The synthetic peptides thus contain the 20-mer T-cell epitope at the N terminus of the construct, immediately followed by the minimal P. falciparum NANP repeat, (NANP) 3 .…”

Section: Vol 70 2002 P Vivax Promiscuous T-cell Epitopes and Immunmentioning

confidence: 99%

Plasmodium vivaxPromiscuous T-Helper Epitopes Defined and Evaluated as Linear Peptide Chimera Immunogens

et al. 2002

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Clinical trials of malaria vaccines have confirmed that parasite-derived T-cell epitopes are required to elicit consistent and long-lasting immune responses. We report here the identification and functional characterization of six T-cell epitopes that are present in the merozoite surface protein-1 of Plasmodium vivax (PvMSP-1) and bind promiscuously to four different HLA-DRB1‫ء‬ alleles. Each of these peptides induced lymphoproliferative responses in cells from individuals with previous P. vivax infections. Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice. A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective. Two out of the six promiscuous T-cell epitopes exhibiting the highest antipeptide response also contain B-cell epitopes. Antisera generated against these B-cell epitopes recognize P. vivax merozoites in immunofluorescence assays. Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes. These data and the simplicity of design of the chimeric constructs highlight the potential of multimeric, multistage, and multispecies linear-peptide chimeras containing parasite promiscuous T-cell epitopes for malaria vaccine development.

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“…With SFV, it has been reported that antibody to one of the peptides of E2, which can induce T cell proliferation, neutralized virus-infected cells in vitro, whereas the antibody to the helper T cell epitopes (E2 T h peptides 1 and 2 ), did not (Snijders et al, 1991, Fernandez et al, 1998). In the SFV model, γδ T cells appeared to play a role as helper cells in antibody production to E2-T h peptide 2, which in turn promoted recovery and regulated remyelinaing mechanisms.…”

Section: - Discussionmentioning

confidence: 99%

Role of γδ T cells in antibody production and recovery from SFV demyelinating disease

Safavi

Feliberti

Raine

et al. 2011

Journal of Neuroimmunology

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Semliki Forest Virus (SFV) encephalomyelitis has been used to study the pathogenesis of virus-induced demyelination and serves as a model for multiple sclerosis. SFV-infection of mice invariably leads to clinical weakness accompanied by CNS inflammation, viral clearance and primary demyelination by day 21 postinfection (pi), followed by recovery and remyelination by day 35 pi. We have applied this model to examination the effects of γδ T cells in antibody production and the pathogenesis of demyelinating lesions. SFV-infection of γδ T cell KO mice resulted in more severe clinical signs than in wild type (WT) B6 mice. SFV-infected WT and γδ KO mice both cleared virus by day 10 pi and inflammation was comparable. Demyelination also appeared to be similar in both groups except that KO mice did not exhibit extensive remyelination which was seen in WT mice by day 21. SFV-infected WT mice showed widespread remyelination by day 35 pi, whereas KO mice still displayed some demyelination through day 42 pi. Both WT and KO mice developed serum antibodies to SFV. However, the reactivity of WT sera with the SFV epitope, E2 Th peptide2, was significantly higher than in KO sera. Immunization with E2 Th peptide2 resulted in elevated antibody production to this peptide (p<0.05) and earlier remyelination (day 28 pi) in KO mice. Thus, our study has shown for the first time that immunization of SFV-infected γδ T cell KO mice with a viral peptide, E2 Th peptide2, led to enhanced recovery and repair of the CNS.

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Epitope polarity and adjuvants influence the fine specificity of the humoral response against Semliki Forest virus specific peptide vaccines

Cited by 7 publications

References 16 publications

Prefusion Rearrangements Resulting in Fusion Peptide Exposure in Semliki Forest Virus

Prefusion Rearrangements Resulting in Fusion Peptide Exposure in Semliki Forest Virus

Plasmodium vivaxPromiscuous T-Helper Epitopes Defined and Evaluated as Linear Peptide Chimera Immunogens

Role of γδ T cells in antibody production and recovery from SFV demyelinating disease

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