Gibbs C J, Peters R, Gravell M, Johnson B K, Jensen F C, Carlo D J, Salk J
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3348-52. doi: 10.1073/pnas.88.8.3348.
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.
两只4年前感染了人类免疫缺陷病毒（HIV）的HIV血清反应阳性黑猩猩（A - 3和A - 86c），以及一只未感染的动物（A - 36），在一年中肌肉注射三次经γ射线照射且去除gp120的HIV免疫原，并佐以不完全弗氏佐剂。两只先前已感染的动物在首次注射后迅速产生了回忆性体液抗体反应，而未感染的动物对首次注射产生了初次体液反应，然后对第二次注射产生了回忆性反应。尽管曾多次从血清反应阳性动物中分离出HIV，但在首次接种免疫原时或之前，它们持续呈病毒培养阴性。在三只接受治疗的黑猩猩和一只未治疗的对照动物（A - 189a）第三次接种4个月后，用40个黑猩猩感染剂量的异源HIV毒株（HIVIIIB）进行静脉内攻击。免疫的未感染动物（A - 36）和未免疫的对照动物（A - 189a）被感染，并且在攻击后2年多的时间里从它们的外周血单核细胞中分离出了病毒。然而，两只先前已感染的黑猩猩（A - 3和A - 86c）抵抗了攻击，并且在攻击后的2年多观察期内，通过外周血单核细胞共培养仍保持病毒阴性；此外，通过PCR未检测到再感染的证据。然而，尽管有体内抗性，但抗性动物（A - 3、A - 86c）的外周血单核细胞在体外仍易受HIV感染。这些发现表明，在黑猩猩中可以产生和/或诱导出一种免疫状态来控制和/或预防HIV感染。在A - 3中未检测到任何可中和抗体水平，在A - 86c中水平较低，这四只动物对攻击的反应模式表明，细胞介导的免疫机制在抗性黑猩猩控制其HIV感染以及抵抗攻击方面一定发挥了重要作用。
