EFFECT OF NONPROTECTIVE VACCINATION ON ANTIBODY-RESPONSE TO SUBSEQUENT HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

We have investigated the systemic anti-HIV antibody response in chimpa nzees who were immunized,vith live vaccinia containing either the HIV envelope glycoprotein (gp160(IIIB)) or a control antigen (herpes simpl ex virus glycoprotein D) and then challenged with either a high dose ( 300,000 TCID50) or low dose(100 TCID50) of HIVIIIB. HIV was subsequent ly isolated from all animals, indicating failure of the vaccination to protect against HIV infection. Serum antibody responses were evaluate d before immunization, at the time of challenge with HIV, and at multi ple 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 anima ls. Antibodies to the V3 loop induced upon infection were unaffected b y immunization. In low dose animals, neutralizing antibody rose more r apidly and to higher levels in the immunized animals as compared with the control. There was no difference in neutralizing antibodies betwee n immunized and control chimpanzees in the high dose group. Epitope ma pping of the anti-gp160 response indicated that immunization with gp16 0 vaccinia induced a postinfection antibody response to a region of gp 41 (amino acids 718-743) that was not immunogenic in control-vaccinate d animals. These data indicate that failed vaccination with the HIV en velope can alter both the timing and epitope specificity of the subseq uent anti-HIV antibody response. These studies also define the evoluti on and fine specificity of the antibody response during the critical p eriod immediately postinfection.