联合免疫治疗后HIV-1控制的相关因素，这一成果由加州大学R. L. Rutishauser团队经过不懈努力而取得。这一研究成果于2025年12月1日发表在国际顶尖学术期刊《自然》上。

该研究组在10名接受ART治疗的HIV患者中进行了一项单组概念验证研究，结合以下三种方法：(1)治疗性疫苗接种HIV/Gag保守元件（CE）靶向DNA+IL-12 prime/MVA增强方案，然后(2)在ART抑制期间给予两种bNAbs （10-1074, VRC07-523LS）和一种toll样受体9激动剂（来非利莫），然后(3)在ART中断时重复给予bNAb （NCT04357821）。10名参与者中有7名在停止抗逆转录病毒治疗后表现出干预后的控制，与残留bNAb血浆水平无关。应答病毒反弹的早期活化CD8+ T细胞的增殖与抗逆转录病毒治疗后病毒峰值后中位病毒载量的降低相关。这些数据表明，联合免疫治疗方法可能通过减缓反弹和改善CD8+ T细胞反应来有效地诱导HIV的持续控制，并且这些方法应该继续优化。

据了解，确定治疗策略以诱导持续抗逆转录病毒治疗（ART）控制HIV感染是一个主要的优先事项包括HIV疫苗接种、免疫刺激/潜伏期逆转和广泛中和抗体（bNAbs）的被动转移在内的联合免疫疗法在非人灵长类动物模型中显示出前景，但将此类方法转化应用于人体的研究尚少。

附：英文原文

Title: Correlates of HIV-1 control after combination immunotherapy

Author: Peluso, M. J., Sandel, D. A., Deitchman, A. N., Kim, S. J., Dalhuisen, T., Tummala, H. P., Tibrcio, R., Zemelko, L., Borgo, G. M., Singh, S. S., Schwartz, K., Deswal, M., Williams, M. C., Hoh, R., Shimoda, M., Narpala, S., Serebryannyy, L., Khalili, M., Vendrame, E., SenGupta, D., Whitmore, L. S., Tisoncik-Go, J., Gale, M., Koup, R. A., Mullins, J. I., Felber, B. K., Pavlakis, G. N., Reeves, J. D., Petropoulos, C. J., Glidden, D. V., Spitzer, M. H., Gama, L., Caskey, M., Nussenzweig, M. C., Chew, K. W., Henrich, T. J., Yukl, S. A., Cohn, L. B., Deeks, S. G., Rutishauser, R. L.

Issue&Volume: 2025-12-01

Abstract: The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority.1 Combination immunotherapy including HIV vaccination, immune stimulation/latency reversal, and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models,2–6 but few studies have translated such approaches into people. We performed a single-arm, proof-of-concept study in ten people with HIV on ART combining the following three approaches: (1) therapeutic vaccination with an HIV/Gag conserved element (CE)-targeted DNA+IL-12 prime/MVA boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (NCT04357821). Seven of the ten participants exhibited post-intervention control after stopping ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8+ T cells early in response to rebounding virus correlated with lower median viral load following peak viremia off ART. These data suggest that combination immunotherapy approaches might prove effective to induce sustained control of HIV by slowing rebound and improving CD8+ T cell responses, and that these approaches should continue to be optimized.

DOI: 10.1038/s41586-025-09929-5

Source: https://www.nature.com/articles/s41586-025-09929-5