Gómez Carmen Elena, Perdiguero Beatriz, García-Arriaza Juan, Cepeda Victoria, Sánchez-Sorzano Carlos Óscar, Mothe Beatriz, Jiménez José Luis, Muñoz-Fernández María Ángeles, Gatell Jose M, López Bernaldo de Quirós Juan Carlos, Brander Christian, García Felipe, Esteban Mariano
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
IrsiCaixa-HIVACAT, Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona, Badalona, Spain.
PLoS One. 2015 Nov 6;10(11):e0141456. doi: 10.1371/journal.pone.0141456. eCollection 2015.
Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART.
The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination.
MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses.
MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.
ClinicalTrials.gov NCT01571466.
先前的研究表明，基于痘病毒的疫苗可能在HIV治疗领域发挥作用。对接受高效抗逆转录病毒疗法（HAART）、CD4 T细胞计数高于450个细胞/mm³且病毒血症检测不到的HIV-1感染患者进行了一项I期临床试验。30名参与者被随机分组（2:1），分别接受3次肌肉注射MVA-B疫苗（编码B亚型HIV-1包膜蛋白、衣壳蛋白、聚合酶蛋白和负调控因子抗原）或安慰剂，随后中断HAART。
通过细胞内细胞因子染色（ICS）检测22名志愿者接种疫苗前后HIV-1特异性T细胞反应的强度、广度、质量和表型。
MVA-B疫苗诱导了新检测到的HIV-1特异性CD4 T细胞反应，并扩大了先前存在的反应（主要针对衣壳蛋白、聚合酶蛋白和负调控因子抗原），这些反应强度高、具有广泛的针对性，并且表现出具有T效应记忆（TEM）表型的增强的多功能性，同时维持了先前存在的HIV-1特异性CD8 T细胞反应的强度和质量。此外，接种疫苗还引发了对MVA载体抗原的优先CD8 + T细胞多功能反应，在两次和三次加强剂量后反应强度增加。
MVA-B疫苗接种是改善已有HIV-1特异性免疫力个体T细胞反应的可行策略。
ClinicalTrials.gov NCT01571466。
