Université François-Rabelais, UFR Médecine, Inserm U966 10 bld Tonnellé, cedex, 37032 Tours, France.
Retrovirology. 2013 Oct 7;10:103. doi: 10.1186/1742-4690-10-103.
In most viral infections, protection through existing vaccines is linked to the presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30 years after the identification of AIDS, the design of an immunogen able to induce antibodies that would neutralize the highly diverse HIV-1 variants remains one of the most puzzling challenges of the human microbiology. The role of antibodies in protection against HIV-1 can be studied in a natural situation that is the mother-to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy, maternal antibodies of the IgG class are passively transferred to the fetus protecting the neonate from new infections during the first weeks or months of life. During the last few years, strong data, presented in this review, have suggested that some NAbs might confer protection toward neonatal HIV-1 infection. In cases of transmission, it has been shown that the viral population that is transmitted from the mother to the infant is usually homogeneous, genetically restricted and resistant to the maternal HIV-1-specific antibodies. Although the breath of neutralization was not associated with protection, it has not been excluded that NAbs toward specific HIV-1 strains might be associated with a lower rate of MTCT. A better identification of the antibody specificities that could mediate protection toward MTCT of HIV-1 would provide important insights into the antibody responses that would be useful for vaccine development. The most convincing data suggesting that NAbs might confer protection against HIV-1 infection have been obtained by experiments of passive immunization of newborn macaques with the first generation of human monoclonal broadly neutralizing antibodies (HuMoNAbs). However, these studies, which included only a few selected subtype B challenge viruses, provide data limited to protection against a very restricted number of isolates and therefore have limitations in addressing the hypervariability of HIV-1. The recent identification of highly potent second-generation cross-clade HuMoNAbs provides a new opportunity to evaluate the efficacy of passive immunization to prevent MTCT of HIV-1.
在大多数病毒感染中，通过现有疫苗获得的保护与疫苗诱导的中和抗体（NAb）的存在有关。然而，在艾滋病被发现 30 多年后，设计一种能够诱导能够中和高度多样化的 HIV-1 变体的抗体的免疫原仍然是人类微生物学中最令人困惑的挑战之一。可以在自然情况下研究针对 HIV-1 的抗体的保护作用，这种自然情况就是母婴传播（MTCT）背景。事实上，至少在妊娠末期，IgG 类别的母体抗体被动转移到胎儿中，使新生儿在生命的最初几周或几个月免受新的感染。在过去的几年中，本综述中提出的强有力的数据表明，一些 NAb 可能对新生儿 HIV-1 感染提供保护。在发生传播的情况下，已经表明从母亲传播到婴儿的病毒群体通常是同质的、遗传受限的，并且对母体 HIV-1 特异性抗体具有抗性。尽管中和的广度与保护无关，但尚未排除针对特定 HIV-1 株的 NAb 可能与较低的 MTCT 率相关。更好地确定可能介导对 HIV-1 MTCT 的保护的抗体特异性，将为针对 HIV-1 的疫苗开发提供有用的抗体反应提供重要的见解。通过用第一代人类单克隆广泛中和抗体（HuMoNab）对新生恒河猴进行被动免疫接种实验，获得了最令人信服的表明 NAb 可能提供针对 HIV-1 感染的保护的数据。然而，这些研究仅包括少数选定的 B 亚型挑战病毒，提供的数据仅限于对非常有限数量的分离物的保护，因此在解决 HIV-1 的高变异性方面存在局限性。最近鉴定出的高效第二代跨属 HuMoNab 提供了评估被动免疫接种预防 HIV-1 MTCT 的功效的新机会。
