Julg Boris, Stephenson Kathryn E, Tomaka Frank, Walsh Stephen R, Sabrina Tan C, Lavreys Ludo, Sarnecki Michal, Ansel Jessica L, Kanjilal Diane G, Jaegle Kate, Speidel Tessa, Nkolola Joseph P, Borducchi Erica N, Braams Esmee, Pattacini Laura, Burgess Eleanor, Ilan Shlomi, Bartsch Yannic, Yanosick Katherine E, Seaman Michael S, Stieh Daniel J, van Duijn Janine, Willems Wouter, Robb Merlin L, Michael Nelson L, Walker Bruce D, Pau Maria Grazia, Schuitemaker Hanneke, Barouch Dan H
Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
Beth Israel Deaconess Medical Center, Boston, MA, USA.
NPJ Vaccines. 2024 May 23;9(1):89. doi: 10.1038/s41541-024-00876-2.
Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.
镶嵌型HIV-1疫苗已被证明能在急性感染期间开始抗逆转录病毒治疗（ART）的HIV-1感染者（PLWH）中引发强烈的体液免疫和细胞免疫反应。我们评估了两种镶嵌型疫苗方案在慢性感染期开始接受ART治疗的病毒学抑制个体中的安全性和免疫原性，这些个体代表了大多数PLWH。在这项双盲、安慰剂对照的1期试验（IPCAVD013/HTX1002）中，25名接受ART治疗且病毒得到抑制的PLWH被随机分为三组，分别接受Ad26.Mos4.HIV/MVA-镶嵌型疫苗（Ad26/MVA）（n = 10）、Ad26.Mos4.HIV/Ad26.Mos4.HIV加佐剂化gp140蛋白（Ad26/Ad26+gp140）（n = 9）或安慰剂（n = 6）。主要终点包括安全性和耐受性，次要终点包括HIV特异性结合和中和抗体滴度以及HIV特异性T细胞反应。两种疫苗方案耐受性良好，注射部位疼痛/压痛以及疲劳、肌痛/寒战和头痛分别是最常报告的预期局部和3级全身不良事件。在Ad26/Ad26+gp140组中，Env特异性IFN-γ T细胞反应中位数增加了12倍，而对Gag和Pol的反应分别增加了1.8倍和2.4倍。Ad26/Ad26+gp140组中，T细胞对各个肽亚池的反应广度从接种前的11.0增加到26.0，Ad26/MVA组从10.0增加到14.5。Ad26/Ad26+gp140疫苗接种使针对疫苗匹配的C亚型Env的结合抗体滴度增加了5.5倍，针对C亚型假病毒的中和抗体滴度增加了7.2倍。两种疫苗方案均具有免疫原性，而添加蛋白加强剂导致额外的T细胞反应以及结合和中和抗体滴度增加。这些数据表明，Ad26/Ad26+gp140方案应进一步进行测试。
