Irsicaixa AIDS Research Institute-HIVACAT, Hospital Germans Trias i Pujol, Badalona, Spain 'Lluita contra la Sida' Foundation, Hospital Germans Trias i Pujol, Badalona, Spain Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), Vic, Spain.
Hospital Clinic-HIVACAT, IDIBAPS, University of Barcelona, Barcelona, Spain.
J Antimicrob Chemother. 2015;70(6):1833-42. doi: 10.1093/jac/dkv046. Epub 2015 Feb 26.
The safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed.
HIV-1-infected patients were randomized to receive three injections of MVA-B (n = 20) or placebo (n = 10). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466.
MVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/10(6) PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P = 0.02 and P = 0.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P = 0.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment.
MVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1-infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram.
评估以重组改良安卡拉痘苗病毒（MVA-B）为基础的（MVA-B）HIV-1 疫苗表达单体 gp120 和融合 gag-pol-nef 多蛋白的 clade B 治疗性 HIV-1 疫苗接种的安全性、免疫原性、对潜伏储库的影响和病毒载量的反弹，以及使用或不使用重新激活潜伏 HIV-1 的药物（安非他酮）的效果。
HIV-1 感染患者被随机分为三组，分别接受三剂 MVA-B（n=20）或安慰剂（n=10）。12 名患者（8 名接受疫苗，4 名接受安慰剂）接受了第四剂 MVA-B 接种，随后接受了 3 个月的安非他酮治疗。在最后一次 MVA-B 剂量后 8 周停止联合抗逆转录病毒治疗（cART）。临床试验.gov 标识符：NCT01571466。
MVA-B 是安全且耐受良好的。观察到针对 gag 疫苗插入物的 T 细胞反应略有增加[基线时中位数为 290、403 和 435 个斑点形成细胞/10（6）个 PBMCs，分别为两次接种后和三次接种后；P=0.02 和 P=0.04]。在中断 cART 后，与安慰剂组相比，接受疫苗但未接受安非他酮的参与者的血浆病毒载量反弹略有延迟（P=0.01）。在接受 MVA-B/安非他酮治疗的患者中，病毒载量反弹的动力学没有改变。在接受安非他酮治疗后，没有观察到前病毒库的变化。
MVA-B 疫苗接种是一种安全的策略，可以增加慢性 HIV-1 感染个体中 gag 特异性 T 细胞反应，但单独使用或与安非他酮联合使用时，对潜伏储库或中断 cART 后血浆病毒载量的反弹没有重大影响。
