Fine analysis of immunoreactivity of V3 peptides: antibodies specific for V3 domain of laboratory HIV type 1 strains recognize multiple V3 sequences synthesized from field HIV type 1 isolates.
Production of cross-reactive antibodies recognizing the V3 loop--that is, the principal neutralizing determinant (PND)--of various HIV-1 isolates is an important challenge in the development of passive immunotherapy or vaccinations against AIDS. We have produced two types of antibodies to the V3 domain of HIV-1: (1) antibodies against the HIV-1 MN laboratory strain generated in rabbits and (2) antibodies targeted to the HIV-1 LAI laboratory strain induced in chimpanzees. These antibodies were shown to be specific for HIV-1 subtype B. The cross-reactivity of these antibodies has been evaluated against a large panel of peptides representing different parts of the V3 loop. Seventy-five peptides, referred to as clinical peptides, were synthesized according to HIV-1 sequences recovered from PMBCs of 27 patients followed in three Parisian hospitals. Thirteen V3 peptides derived from 4 HIV-1 laboratory strains (MN, LAI, SF2, and RF) were also included in the study. The results show that both the amino-terminal and central parts of the V3 loop are immunogenic. The rabbit antibodies against the amino-terminal end of the PND proved to be highly cross-reactive against the clinical peptides. The anti-gp160 antibodies induced in one chimpanzee recognized a significant proportion of the panel of V3 clinical sequences. These antibodies cross-reacted mainly with the apex of the V3 loop. These data give some additional indications on the immunogenicity of the V3 loop and further demonstrate that extensive cross-reactivity of anti-V3 antibodies can be obtained on field HIV-1 isolates despite the high variability of the V3 loop amino acid sequence.
Boudet
F
F
Facultad de Medicina, Departamento de Medicina Interna, Universidad de Navarra, Pamplona, Spain.
Lasarte
J J
JJ
Sarobe
P
P
Borras-Cuesta
F
F
Theze
J
J
D000818:Animals; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D002679:Pan troglodytes; D010446:Peptide Fragments / Q000276:immunology*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins