Document Detail


DNA vaccination of macaques with several different Nef sequences induces multispecific T cell responses.
MedLine Citation:
PMID:  11145897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CD8(+) T lymphocytes play a key role in controlling viremia during primary human immunodeficiency virus-1 and in maintaining disease-free infection. It has recently been shown that DNA immunization of rhesus monkeys can elicit strong, long-lived antigen-specific cytotoxic T lymphocyte (CTL) responses. In previous work, it was shown that macaque CTL responses to lipopeptide vaccination were directed against a limited number of epitopes. In the present study, we used the DNA immunization approach to enlarge T cell responses to several epitopes and to multiple isolates. We immunized macaques with a mixture of six plasmids reflecting the variability of Nef epitopic regions in the simian immunodeficiency virus (SIV) mac251 primary isolate. The Nef genes from viruses included in the SIVmac251 primary isolate were sequenced and the six selected sequences were individually subcloned into the pCI vector, under cytomegalovirus enhancer/promoter control, and injected into macaques. We show that DNA immunization with Nef sequences induced interferon-gamma (IFN-gamma) secreting cell responses directed against several regions of Nef. Reacting T cell lines were expanded in vitro and multispecific CTL responses mapping the 96-138 Nef region were analyzed. Several peptides recognized by CTL were identified and studies using peptides reflecting the variability of Nef indicated that all of the Nef variants were recognized in the 96-138 region. Moreover, CTL responses were directed against an immunodominant epitope located in a functional region within the Nef protein that is essential for viral replication. This work shows that our approach of DNA immunization with several sequences induced multispecific T cell responses recognizing variants included in the SIVmac251 primary isolate.
Authors:
I Couillin; F Letourneur; P Lefèbvre; J G Guillet; F Martinon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Virology     Volume:  279     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-26     Completed Date:  2001-03-01     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  136-45     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM U445, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cytotoxicity Tests, Immunologic
Gene Products, nef / chemistry,  genetics,  immunology*
Genetic Variation
Interferon-gamma / biosynthesis
Macaca mulatta
Male
Molecular Sequence Data
Reverse Transcriptase Polymerase Chain Reaction
SAIDS Vaccines / immunology*
Simian Acquired Immunodeficiency Syndrome / immunology,  prevention & control
Simian immunodeficiency virus / immunology*
T-Lymphocytes, Cytotoxic / immunology*
Vaccination
Vaccines, DNA / immunology*
Chemical
Reg. No./Substance:
0/Gene Products, nef; 0/SAIDS Vaccines; 0/Vaccines, DNA; 82115-62-6/Interferon-gamma

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