Observations after human immunodeficiency virus immunization and challenge of human immunodeficiency virus seropositive and seronegative chimpanzees.
Two human immunodeficiency virus (HIV)-seropositive chimpanzees (A-3 and A-86c) infected 4 yr earlier with HIV, along with one uninfected animal (A-36), were inoculated intramuscularly three times in a year with a gamma-irradiated gp120-depleted HIV immunogen in incomplete Freund's adjuvant. Both previously infected animals promptly developed an anamnestic humoral antibody response after the first dose, and the uninfected animal developed a primary humoral response to the first dose and then an anamnestic response to the second dose. Although HIV had been recovered repeatedly from the seropositive animals, they became persistently virus-culture negative at the time of or just before the first inoculation of the immunogen. Intravenous challenge with 40 chimpanzee-infectious-doses of a heterologous HIV strain (HIVIIIB) was done 4 mo after the third inoculation in the three treated chimpanzees and in an untreated control animal (A-189a). The immunized naive animal (A-36) and the unimmunized control (A-189a) became infected, and virus has been isolated from their peripheral blood mononuclear cells for greater than 2 yr after challenge. However, the two previously infected chimpanzees (A-3 and A-86c) resisted challenge and have remained virus negative by peripheral blood mononuclear cell cocultivation for greater than 2 yr of observation after challenge; moreover, no evidence of reinfection was detectable by PCR. Despite the in vivo resistance, however, peripheral blood mononuclear cells from the resistant animals (A-3, A-86c) remained susceptible to infection by HIV in vitro. These findings reveal that a state of immunity can develop and/or be induced to control and/or prevent HIV infection in the chimpanzees. In the absence of any detectable level of neutralizing antibody in A-3 and a low level in A-86c, the patterns of the responses to challenge seen in the four animals suggest that the cell-mediated immune mechanism must have played a significant role in the resistant chimpanzees both in control of their HIV infection and in their resistance to challenge.
Gibbs
C J
CJ
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Peters
R
R
Gravell
M
M
Johnson
B K
BK
Jensen
F C
FC
Carlo
D J
DJ
Salk
J
J
D000818:Animals; D015483:HIV Antibodies / Q000096:biosynthesis*; D015658:HIV Infections / Q000517:prevention & control*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D002679:Pan troglodytes / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D015483:HIV Antibodies; D014765:Viral Vaccines