Mouquet Hugo
Institut Pasteur, Université Paris Cité, Humoral Immunology Unit, Paris, France.
Curr Opin HIV AIDS. 2025 Jan 1;20(1):80-85. doi: 10.1097/COH.0000000000000893. Epub 2024 Nov 7.
Decoding the HIV-1 immune response, including its humoral arm, in post-treatment controllers (PTCs) is paramount to unveil immune correlates of viral control, which could help developing novel strategies towards HIV-1 remission. Here, we review novel findings on the humoral response to HIV-1 in PTCs.
New data reveal the heterogeneity of humoral immune profiles in PTCs, principally influenced by viral exposure and dynamics. Stably aviremic PTCs, akin early ART-treated individuals, show minimal antibody B-cell response. Conversely, virally exposed PTCs develop functionally coordinated and effective humoral responses to HIV-1. They can produce antibodies cross-neutralizing heterologous HIV-1 viruses, including broadly neutralizing antibodies (bNAbs) exerting selective immune pressure. PTCs also elicit neutralizing antibodies against contemporaneous autologous viruses presumed to play a major role in sustaining viral suppression.
The immune mechanisms underlying virologic control in PTCs likely involve various immune effectors. Notably, functional HIV-1 humoral responses can generate bNAbs and autologous neutralizing antibodies; however, their exact contribution to maintaining long-term control of plasma viremia and the precise mechanisms driving their induction require further investigation.
解读治疗后病毒控制者（PTCs）的HIV-1免疫反应，包括其体液免疫分支，对于揭示病毒控制的免疫相关因素至关重要，这有助于开发针对HIV-1缓解的新策略。在此，我们综述了PTCs中针对HIV-1的体液反应的新发现。
新数据揭示了PTCs体液免疫谱的异质性，主要受病毒暴露和动态变化的影响。稳定病毒血症阴性的PTCs，类似于早期接受抗逆转录病毒治疗的个体，显示出最小的抗体B细胞反应。相反，有病毒暴露的PTCs对HIV-1产生功能协调且有效的体液反应。它们可以产生交叉中和异源HIV-1病毒的抗体，包括发挥选择性免疫压力的广泛中和抗体（bNAbs）。PTCs还能引发针对同期自体病毒的中和抗体，推测这些抗体在维持病毒抑制中起主要作用。
PTCs中病毒学控制的免疫机制可能涉及多种免疫效应器。值得注意的是，功能性HIV-1体液反应可产生bNAbs和自体中和抗体；然而，它们对维持血浆病毒血症长期控制的确切贡献以及驱动其诱导的精确机制仍需进一步研究。
