1. Effect of Natural HIV-1 Envelope V1-V2 Sequence Diversity on the Binding of V3-Specific and Non-V3-Specific Antibodies
- Author
-
Julia L. Hurwitz and S.D. Rencher
- Subjects
HIV Antigens ,medicine.drug_class ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Immunology ,HIV Antibodies ,HIV Envelope Protein gp120 ,Monoclonal antibody ,Epitope ,Epitopes ,chemistry.chemical_compound ,Viral envelope ,Antigen ,Antibody Specificity ,Virology ,Vaccinia ,medicine ,Immunology and Allergy ,Amino Acid Sequence ,Recombination, Genetic ,Genetics ,biology ,Antibodies, Monoclonal ,Vaccine efficacy ,Fusion protein ,Peptide Fragments ,Recombinant Proteins ,chemistry ,HIV-1 ,biology.protein ,Antibody ,Epitope Mapping - Abstract
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.
- Published
- 1997