Induction of antibodies to the human immunodeficiency virus type 1 by immunization of baboons with immunoglobulin molecules carrying the principal neutralizing determinant of the envelope protein.
The hypervariable region 3 (V3) 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 neutralizing 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 V3M) were expressed on the variable region of murine-human immunoglobulin (Ig) chimeras that were designated Ig-V3C and Ig-V3M, respectively. The HIV-1 sequences on the Ig chimeras preserved their antigenicity and interacted with antibodies specific for peptides encompassing the V3C and V3M sequences. In baboons, Ig-V3C and Ig-V3M induced antibodies that bound V3C and V3M peptides as well as the glycoprotein gp120 envelope protein of HIV-1 MN isolate. In addition, the baboons' antisera were able to prevent infection of CD4 SupT1 susceptible T cells by HIV-1 MN. Finally, Ig-V3M chimeras were able to stimulate in vitro production of antibodies specific for the HIV-1 envelope-derived peptides by lymphocytes from HIV-1-infected human subjects.
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
H
H
Zaghouani
S A
SA
Anderson
K E
KE
Sperber
C
C
Daian
R C
RC
Kennedy
L
L
Mayer
C A
CA
Bona
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010215:Papio / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D016056:Immunodominant Epitopes; D007136:Immunoglobulins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic