Effect of natural HIV-1 envelope V1-V2 sequence diversity on the binding of V3-specific and non-V3-specific antibodies.
In past years, much attention has been paid to the HIV-1 envelope (env) protein variable region 3 (V3), termed the principal neutralizing determinant. HIV-1 vaccines were often designed to target V3, and vaccine efficacy was often measured with V3-based assays. Thus, some disappointment resulted when volunteers in first clinical vaccine trials generated V3-specific antibodies that could not protect against V3-similar viruses. We describe an analysis of V1 and V2 sequence effects on antibody binding to V3 and non-V3 determinants. This study involved the preparation of seven full-length (gp160), chimeric env proteins in a vaccinia virus (VV) expression system. Chimeric proteins displayed different V1-V2 sequences but were otherwise identical. A panel of 12 monoclonal antibodies was then tested for binding activities toward the seven chimeras. Results showed that V1-V2 sequences affected antibody binding to env, both in V3 and non-V3 positions. These data demonstrate the enormous complexity of HIV-1 env protein conformation and antigenic determinants. Respect for the complexity of antibody-antigen interactions encourages the design of sophisticated immunoglobulin and protein cocktails for use in HIV-1 therapies and vaccines, respectively.
Rencher
S D
SD
Department of Immunology, St. Jude Children's Research Hospital, University of Memphis, Tennessee, U.S.A.
Hurwitz
J L
JL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D011995:Recombination, Genetic; D014615:Vaccinia / Q000235:genetics
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; C059761:HIV envelope protein gp120 (135-148); C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins