Effect of nonprotective vaccination on antibody response to subsequent human immunodeficiency virus infection.
We have investigated the systemic anti-HIV antibody response in chimpanzees who were immunized with live vaccinia containing either the HIV envelope glycoprotein (gp160IIIB) or a control antigen (herpes simplex virus glycoprotein D) and then challenged with either a high dose (300,000 TCID50) or low dose (100 TCID50) of HIVIIIB. HIV was subsequently isolated from all animals, indicating failure of the vaccination to protect against HIV infection. Serum antibody responses were evaluated before immunization, at the time of challenge with HIV, and at multiple time points in the 9 mo after challenge. Immunization resulted in a more rapid rise of antibody to gp160 in both high and low dose animals. Antibodies to the V3 loop induced upon infection were unaffected by immunization. In low dose animals, neutralizing antibody rose more rapidly and to higher levels in the immunized animals as compared with the control. There was no difference in neutralizing antibodies between immunized and control chimpanzees in the high dose group. Epitope mapping of the anti-gp 160 response indicated that immunization with gp160 vaccinia induced a postinfection antibody response to a region of gp41 (amino acids 718-743) that was not immunogenic in control-vaccinated animals. These data indicate that failed vaccination with the HIV envelope can alter both the timing and epitope specificity of the subsequent anti-HIV antibody response. These studies also define the evolution and fine specificity of the antibody response during the critical period immediately postinfection.
Pincus
S H
SH
Laboratory of Microbial Structure and Function, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840.
Messer
K G
KG
Hu
S L
SL
D016915:AIDS Vaccines / Q000494:pharmacology*; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood*; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D007114:Immunization; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D002679:Pan troglodytes; D011498:Protein Precursors / Q000276:immunology; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000494:pharmacology*
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D009842:Oligopeptides; D011498:Protein Precursors; D014614:Vaccines, Synthetic