Details

Autor(en) / Beteiligte

• Gibbs, Clarence J.
• Peters, Robert
• Gravell, Maneth
• Johnson, Bruce K.
• Jensen, Fred C.
• Carlo, Dennis J.
• Salk, Jonas

Titel

Observations After Human Immunodeficiency Virus Immunization and Challenge of Human Immunodeficiency Virus Seropositive and Seronegative Chimpanzees

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1991-04, Vol.88 (8), p.3348-3352

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1991

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 γ-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 >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 >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.