Berman P W, Eastman D J, Wilkes D M, Nakamura G R, Gregory T J, Schwartz D, Gorse G, Belshe R, Clements M L, Byrn R A
Department of Immunology, Genentech Inc., South San Francisco, California 94080.
AIDS. 1994 May;8(5):591-601. doi: 10.1097/00002030-199405000-00004.
To assess similarities and differences in antibody responses to recombinant (r) HIV-1IIIB gp120 in chimpanzees, previously protected from HIV-1 infection, and human volunteers immunized in connection with a Phase I clinical trial.
Frozen sera from humans immunized with rgp120 from HIV-1IIIB and chimpanzees immunized with the same antigen or recombinant soluble gp160 were compared in a variety of serologic assays.
The magnitude of the antibody response to gp120 was similar in both species; however, the half-life of the antibody response to rgp120 was approximately 4.5 times longer in humans (9 weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both species were broadly cross-reactive with gp120 from diverse isolates of HIV-1 and were effective in blocking the binding of gp120 to CD4. Antibody binding to native gp120 was greater than to denatured gp120 in both species. Antibody responses to the principal neutralizing determinant (V3 domain) and virus neutralization titers were approximately 10-fold lower in humans than chimpanzees. The relative avidity of antibody binding to gp120 was higher in the sera from the immunized chimpanzees than in the immunized humans.
While the antibody responses to rgp120 elicited in man and chimpanzees were in many ways similar, significant differences did occur. Predictions made on the basis of chimpanzee immunogenicity studies over-estimated the potency of the virus neutralizing titers and under-estimated the duration of the antibody response achieved in humans.
评估先前免受HIV-1感染的黑猩猩以及在一项I期临床试验中接种疫苗的人类志愿者对重组（r）HIV-1IIIB gp120抗体反应的异同。
在多种血清学检测中比较了用HIV-1IIIB的rgp120免疫的人类以及用相同抗原或重组可溶性gp160免疫的黑猩猩的冻存血清。
两个物种对gp120的抗体反应强度相似；然而，人类对rgp120的抗体反应半衰期（9周）约为黑猩猩（2周）的4.5倍。两个物种中针对gp120的抗体与多种HIV-1分离株的gp120具有广泛的交叉反应性，并且能有效阻断gp120与CD4的结合。在两个物种中，抗体与天然gp120的结合均大于与变性gp120的结合。人类对主要中和决定簇（V3结构域）的抗体反应和病毒中和滴度比黑猩猩低约10倍。免疫黑猩猩血清中抗体与gp120结合的相对亲和力高于免疫人类的血清。
虽然人类和黑猩猩对rgp120引发的抗体反应在许多方面相似，但确实存在显著差异。基于黑猩猩免疫原性研究做出的预测高估了病毒中和滴度的效力，低估了人类中抗体反应的持续时间。
