Reeves J P, Buck D, Berkower I, Murphy D, Epstein S L
Molecular Immunology Laboratory, FDA, CBER, OBR, DBB, Bethesda, MD 20892.
AIDS Res Hum Retroviruses. 1991 Jan;7(1):55-63. doi: 10.1089/aid.1991.7.55.
Development of a vaccine for acquired immunodeficiency syndrome (AIDS) has proven difficult, and so alternative approaches such as idiotypic manipulation have been suggested. As applied to AIDS, this approach could involve immunizing with an anti-CD4 antibody resembling gp120, to induce anti-idiotypic antibodies which would bind to gp120. The CD4 binding site on gp120 is conserved, and so, such an immune response should protect against all variants. Induction of anti-human immunodeficiency virus (HIV) immunity has been reported using anti-Leu3a, and this result has led to testing in humans. Negative results obtained by others have been attributed to differences in immunization protocols. Because of the importance of this question, we reinvestigated the potential of anti-Leu3a to induce anti-HIV antibodies, compared with control immunizations with OKT4A (another anti-CD4 antibody) and the irrelevant Ig MOPC-21. Responses to anti-Leu3a showed induction of high-titer anti-idiotypic activity, and included combining-site-related activity. Yet sera showed no binding to gp160 above controls and no detectable neutralizing activity in a sensitive HIV plaque assay, so the anti-idiotypes induced were not internal images of CD4. We conclude that the pronounced anti-HIV responses reported with anti-Leu3a cannot be generalized, and thus that anti-Leu3a does not offer promise as an HIV vaccine. However, these results do not negate the promise of the idiotypic approach, and a vaccine for AIDS based on idiotype manipulation remains a possibility.
事实证明，开发一种针对获得性免疫缺陷综合征（艾滋病）的疫苗非常困难，因此有人提出了诸如独特型操纵等替代方法。应用于艾滋病时，这种方法可能涉及用一种类似于gp120的抗CD4抗体进行免疫，以诱导能与gp120结合的抗独特型抗体。gp120上的CD4结合位点是保守的，因此，这样的免疫反应应该能抵御所有变体。据报道，使用抗Leu3a可诱导抗人类免疫缺陷病毒（HIV）免疫，这一结果已促使其进入人体试验阶段。其他人得到的阴性结果被归因于免疫方案的差异。鉴于这个问题的重要性，我们重新研究了抗Leu3a诱导抗HIV抗体的潜力，并与用OKT4A（另一种抗CD4抗体）和无关的Ig MOPC-21进行的对照免疫作了比较。对抗Leu3a的反应显示出高滴度抗独特型活性的诱导，并且包括结合位点相关活性。然而，血清在高于对照的情况下未显示与gp160的结合，并且在灵敏的HIV空斑试验中未检测到中和活性，因此诱导的抗独特型抗体不是CD4的内影像。我们得出结论，抗Leu3a所报道的明显抗HIV反应不能一概而论，因此抗Leu3a作为HIV疫苗没有前景。然而，这些结果并未否定独特型方法的前景，基于独特型操纵的艾滋病疫苗仍然是一种可能性。
