Department of Medicine, Division of Infectious Diseases, University of California, Irvine School of Medicine, Irvine, California, USA.
Curr Opin HIV AIDS. 2009 Sep;4(5):388-93. doi: 10.1097/COH.0b013e32832f0a89.
We summarize current information on Fc receptor-mediated antiviral activities of antibodies. These activities include Fcgamma receptor-mediated inhibition and neutralization of HIV on antigen-presenting cells, antibody-dependent cellular cytotoxicity, and antibody-dependent cell-mediated virus inhibition (ADCVI).
An Fcgamma receptor-mediated mechanism that results in augmented neutralization and may render nonneutralizing antibodies inhibitory has been demonstrated in antigen-presenting cell. Antibody-dependent cellular cytotoxicity antibody activity correlates inversely with HIV disease progression in humans, and higher vaccine-induced antibody-dependent cellular cytotoxicity antibody responses are associated with lower acute simian immunodeficiency virus viremia levels in macaques. Following vaccination with rgp120, ADCVI antibody levels are higher among those with a lower rate of sexually acquired HIV infection. Nonneutralizing simian immunodeficiency virus immune serum that prevents infection of newborn macaques after oral challenge has potent ADCVI antibody activity. Abrogating the ability of the Fc segment of the broadly neutralizing mAb b12 to bind to Fcgamma receptors and to mediate ADCVI substantially reduces b12's protective effect in a simian/human immunodeficiency virus vaginal challenge model.
Fc-FcgammaR interactions play a critical role in the biological function of antibody and are likely to be instrumental in preventing or modulating lentiviral infection. Exploiting antibody responses that depend on Fc-FcgammaR interactions may help widen the breadth and increase the potency of vaccine-induced antibody. Although the importance of generating optimal Fab-antigen interactions cannot be overestimated, improving Fc-FcgammaR interactions through adjuvants or other strategies provides another option for improving HIV vaccines and immunotherapies.
我们总结了抗体 Fc 受体介导的抗病毒活性的最新信息。这些活性包括 Fcγ 受体介导的在抗原呈递细胞上对 HIV 的抑制和中和、抗体依赖性细胞毒性和抗体依赖性细胞介导的病毒抑制（ADCVI）。
在抗原呈递细胞中，已经证明了一种 Fcγ 受体介导的机制，该机制导致增强的中和作用，并可能使非中和抗体具有抑制作用。抗体依赖性细胞毒性抗体活性与人类 HIV 疾病进展呈负相关，疫苗诱导的抗体依赖性细胞毒性抗体反应更高与猕猴急性 simian 免疫缺陷病毒病毒血症水平较低相关。接种 rgp120 后，ADCVI 抗体水平在性传播 HIV 感染率较低的人群中较高。在口服挑战后预防新生猕猴感染的非中和性 simian 免疫缺陷病毒免疫血清具有很强的 ADCVI 抗体活性。消除广泛中和 mAb b12 的 Fc 段与 Fcγ 受体结合并介导 ADCVI 的能力，大大降低了 b12 在 simian/human 免疫缺陷病毒阴道挑战模型中的保护作用。
Fc-FcγR 相互作用在抗体的生物学功能中起着关键作用，并且可能在预防或调节慢病毒感染方面发挥重要作用。利用依赖于 Fc-FcγR 相互作用的抗体反应可能有助于扩大疫苗诱导的抗体的广度并提高其效力。虽然产生最佳 Fab-抗原相互作用的重要性怎么强调都不为过，但通过佐剂或其他策略改善 Fc-FcγR 相互作用为改善 HIV 疫苗和免疫疗法提供了另一种选择。
