VAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4⁺ T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S. This multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial enroled between January 2014 and March 2015 HIV-1-infected patients under ART with plasma HIV RNA levels below 50 copies/mL and CD4 counts between 200 and 500 cells/μL. Participants were immunised with 16, 32, or 64 μg of VAC-3S, and compared to placebo. The primary outcome was immunogenicity assessed by changes from baseline of anti-3S Abs levels at week 12. Secondary outcomes included adverse events and the course of plasma HIV RNA level, CD4 count, CD4/CD8 ratio, inflammation and immune checkpoints from week 0 to week 48. Vaccination was well tolerated with no serious adverse events and induced a significant increase in anti-3S Ab response in vaccinated patients (p < 0.0001), compared to placebo. In high responders, the robust increased of CD4 count was associated with a significant and sustained reduction of PD-1 expression on CD4⁺ T cells through week 48 (variance p = 0.0017). PD-1 expression was correlated with level of anti-3S Abs (p = 0.0092, r = −0.68) and expression of NKp44L (p < 0.0001; r = 0.54) in CD4⁺ T cells. Our findings regarding the increase of non-exhausted CD4⁺ T cells have potentially important application in personalised HIV vaccination for HIV-infected patients with high level of PD-1 to improve their T-cell immune function.

VAC-3S是一种治疗性疫苗，包含高度保守的HIV-gp41基序和CRM197载体蛋白。高水平的抗3S抗体（Abs）与改善的CD4 ⁺保护相关T细胞存活。先前的第1阶段研究证明了VAC-3S的安全性。这项多中心，随机，双盲，安慰剂对照的2期临床试验于2014年1月至2015年3月间接受抗HIV-1感染的ART患者的血浆HIV RNA水平低于50拷贝/ mL，CD4计数介于200至500个细胞/微升 用16、32或64μgVAC-3S免疫参与者，并与安慰剂进行比较。主要结果是通过在第12周时从抗3S Abs水平开始的基线来评估免疫原性。次要结果包括不良事件和血浆HIV RNA水平，CD4计数，CD4 / CD8比，炎症和免疫检查点的过程，从第0周到第48周。接种疫苗的耐受性良好，没有严重的不良事件，并且在接种疫苗的患者中诱导了抗3S Ab反应的显着增加（p  <0.0001），与安慰剂相比。在高应答者中，CD4计数的强劲增加与直至第48周CD4 ⁺ T细胞上PD-1表达的显着且持续降低有关（方差p  = 0.0017）。PD-1表达与 CD4 ⁺ T细胞中抗3S Abs水平（p  = 0.0092，r  = -0.68）和NKp44L表达（p  <0.0001; r = 0.54）相关。我们关于未用尽的CD4 ⁺ T细胞增加的发现在针对HIV感染的高PD-1水平的HIV感染患者的个性化HIV疫苗接种中可能具有重要的应用价值，以改善其T细胞免疫功能。