Document 0277
 DOCN  M9460277
 TI    Simian immunodeficiency virus as a model for vaccination against HIV.
       Induction in rhesus macaques of GAG- or NEF-specific cytotoxic T
       lymphocytes by lipopeptides.
 DT    9404
 AU    Bourgault I; Chirat F; Tartar A; Levy JP; Guillet JG; Venet A; Cochin
       Institute of Molecular Genetics, Cochin Hospital, Paris,; France.
 SO    J Immunol. 1994 Mar 1;152(5):2530-7. Unique Identifier : AIDSLINE
       MED/94179836
 AB    The protection against infection by HIV probably requires the induction
       of both neutralizing Abs and CTL responses. Vaccination by attenuated
       HIV is hardly acceptable and the use of viral genes inserted in
       recombinant living vectors needs further development, especially with
       respect to safety. The peptidic vaccination is a promising approach but
       free peptides are usually poorly immunogenic. Because potent immune
       responses have been obtained in mice with modified peptides such as
       lipopeptides, we have designed a study to assess the immunogenicity of
       lipopeptides in nonhuman primates. Seven lipopeptides were synthesized,
       derived from known immunogenic regions of the simian immunodeficiency
       virus (SIV) NEF and GAG proteins. Twelve rhesus macaques, randomly
       chosen and not selected on their MHC basis, were immunized
       subcutaneously with the seven lipopeptides in IFA. An MHC class
       I-restricted and CD(8+)-mediated CTL response has been observed in seven
       macaques directed against one or two of the synthetic immunizing
       peptides in each case. These CTLs were able to lyse autologous target
       cells infected with a recombinant vaccinia virus expressing the SIV nef
       or gag genes, suggesting that they recognized the naturally processed
       peptides. These activities are detectable in peripheral blood cells for
       at least 10 mo after the last immunization. Abs against the immunizing
       peptides have also been observed in all cases. This study demonstrates
       that lipopeptides can generate cytotoxic and humoral immune responses in
       a large number of unselected animals and this approach may thus be worth
       considering in the vaccination against HIV.
 DE    Amino Acid Sequence  Animal  AIDS Vaccines/IMMUNOLOGY  Gene Products,
       gag/GENETICS/IMMUNOLOGY  Gene Products, nef/GENETICS/IMMUNOLOGY  HIV
       Infections/*PREVENTION & CONTROL  Kinetics
       Lipoproteins/GENETICS/IMMUNOLOGY  Macaca mulatta  Major
       Histocompatibility Complex  *Models, Biological  Molecular Sequence Data
       Peptide Fragments/GENETICS/IMMUNOLOGY  Support, Non-U.S. Gov't
       SIV/*GENETICS/*IMMUNOLOGY  T-Lymphocytes, Cytotoxic/IMMUNOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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