INDUCTION OF ANTIBODIES TO THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BYIMMUNIZATION OF BABOONS WITH IMMUNOGLOBULIN MOLECULES CARRYING THE PRINCIPAL NEUTRALIZING DETERMINANT OF THE ENVELOPE PROTEIN

The hypervariable region 3 (V-3) within the disulfide-bridged loop of the envelope protein of the human immunodeficiency virus type 1 (HIV-1 ) contains an amino acid sequence that was defined as a principal neut ralizing determinant (PND). A 19-amino acid residue consensus sequence (designated V3C) predicted from the PND sequences of 245 isolates as well as a sequence from the PND of the WMJ2 HIV-1 isolate (designated V(3)M) were expressed on the variable able region of murine-human immu noglobulin (Ig) chimeras that were designated Ig-V3C and Ig-V(3)M, res pectively. The HIV-1 sequences on the Ig chimeras preserved their anti genicity and interacted with antibodies specific for peptides encompas sing the V3C and V(3)M sequences. In baboons, Ig-V3C and Ip-V(3)M indu ced antibodies that bound V3C and V(3)M peptides as well as the glycop rotein gp120 envelope protein of HIV-1 MN isolate. In addition, the ba boons' antisera were able to prevent infection of CD4 SupT1 susceptibl e T cells by HIV-1 MN. Finally, Ig-V(3)M chimeras were able to stimula te in vitro production of antibodies specific for the HIV-1 envelope-d erived peptides by lymphocytes from HIV-1-infected human subjects.