Document 0052
 DOCN  M9590052
 TI    Single peptide and anti-idiotype based immunizations can broaden the
       antibody response against the variable V3 domain of HIV-1 in mice.
 DT    9509
 AU    Boudet F; Keller H; Kieny MP; Theze J; Unite d'Immunogenetique
       Cellulaire, Institut Pasteur, Paris,; France.
 SO    Mol Immunol. 1995 May;32(7):449-57. Unique Identifier : AIDSLINE
       MED/95303114
 AB    The third variable (V3) domain of the human immunodeficiency virus type
       1 (HIV-1) external envelope glycoprotein gp120 is a major target of
       neutralizing antibodies in infected persons and in experimental
       immunized animals. Given the high degree of sequence variability of V3,
       the humoral response toward this region is very type-specific. In the
       present study, we evaluated the potential of a single peptide and an
       anti-idiotypic antibody to broaden the anti-V3 antibody specificity in
       BALB/c mice. We show that a synthetic peptide derived from the V3
       determinant of HIV-1 MN isolate (V3MN), when used as an immunogen, was
       able to induce an antibody response to multiple (up to six) HIV-1
       strains. The extent of this cross-reactivity, which tended to enlarge as
       the injections increased, appeared to be inversely correlated with the
       binding affinity to V3MN peptide. These data thus present evidence that,
       despite its great sequence heterogeneity, the V3 loop encompasses
       conserved amino-acid positions and/or stretches which may be less
       immunogenic than their variable counterparts. We additionally
       demonstrate that a rabbit anti-idiotype (Ab2), recognizing a binding
       site related idiotype on a V3-specific mouse monoclonal antibody (Ab1),
       could mount a broadened humoral response (Ab3) in mice. Unlike nominal
       antibody Ab1 which strictly reacted with the European HIV-1 LAI isolate,
       elicited Ab3 recognized the two divergent HIV-1 strains SF2 and 1286,
       originating respectively from North America and Central Africa, in
       addition to LAI. The reasons accounting for this Ab2-induced enlargement
       of the V3 antibody response are discussed. Our findings suggest that
       single peptide and anti-idiotype based immunizations may provide viable
       approaches to overcome, at least in part, HIV epitope variability.
 DE    Amino Acid Sequence  Animal  Antibodies, Anti-Idiotypic  AIDS
       Vaccines/IMMUNOLOGY/ISOLATION & PURIF  Carrier Proteins/IMMUNOLOGY
       Cross Reactions  Female  Human  HIV Antibodies/*BIOSYNTHESIS  HIV
       Envelope Protein gp120/GENETICS/*IMMUNOLOGY  HIV-1/GENETICS/*IMMUNOLOGY
       Immunization  Mice  Mice, Inbred BALB C  Molecular Sequence Data
       Neutralization Tests  Peptide Fragments/GENETICS/*IMMUNOLOGY
       Peptides/CHEMICAL SYNTHESIS/GENETICS/IMMUNOLOGY  Rabbits  Recombinant
       Proteins/GENETICS/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).