Lind Andreas, Sommerfelt Maja, Holmberg Jens Olof, Baksaas Ingebjørg, Sørensen Birger, Kvale Dag
Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
Scand J Infect Dis. 2012 Aug;44(8):566-72. doi: 10.3109/00365548.2011.653581. Epub 2012 Feb 19.
Vacc-4x contains 4 HIV p24-like short peptides. In a previous phase II trial this immunized 90% of 38 patients on antiretroviral treatment (ART) after intradermal delivery in conjunction with local granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant. In this study, 22 responders were retested for cellular memory at a median 7.3 y after their last immunization. All had resumed effective ART after an interspersed ART-free median interval of 2.2 y.
Vacc-4x as 15-mer overlapping by 2 amino acid panels and Vacc-4x consensus peptide sequences (4xCP) were used as antigens. Proliferation was determined as percentages of CFSE(dim)HLA-DR(+) 7AAD(-) CD3+ T cells of the CD4+ and CD8+ subsets after 6 days of culture. Frequencies of specific T cells in 6-h cultures were determined by interferon-γ (IFN)(+) CD4+ and IFN(+) CD8+, as well as degranulating bifunctional CD107a + IFN(+) CD8 + subsets.
Proliferative CD4+ and CD8+ responses to Vacc-4x as well as 4xCP were still present in 95% and 68%, respectively. Proliferation correlated with the Vacc-4x delayed-type hypersensitivity test (DTH) obtained after completed immunizations (CD4 + r = 0.63 (p = 0.002) and CD8 + r = 0.47 (p = 0.03)), suggesting that they represent T cell memory recall responses. The proliferative CD8+ and possibly CD4 + subset responses to 4xCP peptides correlated with Vacc-4x (r = 0.46 (p = 0.03) and r = 0.38 (p = 0.08), respectively). Forty-one percent still had Vacc-4x-specific IFN + CD4 + T cells, which correlated to corresponding frequencies of 4xCP peptides (r = 0.50, p = 0.02). CD107a(+) IFN(+) CD8 + T cell responses against Vacc-4x were found in 55%.
Evidence of long-lasting T cell memory recall responses to a peptide-based immunotherapeutic candidate for HIV-infected patients should enhance the focus on peptide-based intradermal vaccine delivery.
Vacc-4x包含4种HIV p24样短肽。在先前的一项II期试验中，38例接受抗逆转录病毒治疗（ART）的患者在皮内注射并联合局部粒细胞-巨噬细胞集落刺激因子（GM-CSF）作为佐剂后，90%的患者产生了免疫反应。在本研究中，对22名有反应者在最后一次免疫后中位7.3年进行了细胞记忆重新检测。所有人在中位2.2年的无ART间隔后都恢复了有效的ART治疗。
使用由2个氨基酸重叠的15聚体Vacc-4x和Vacc-4x共有肽序列（4xCP）作为抗原。培养6天后，通过CFSE（dim）HLA-DR（+）7AAD（-）CD3+ T细胞在CD4+和CD8+亚群中的百分比来测定增殖情况。通过干扰素-γ（IFN）（+）CD4+和IFN（+）CD8+以及脱颗粒双功能CD107a + IFN（+）CD8 +亚群来测定6小时培养物中特异性T细胞的频率。
对Vacc-4x以及4xCP的增殖性CD4+和CD8+反应分别仍存在于95%和68%的患者中。增殖与完成免疫后获得的Vacc-4x迟发型超敏反应试验（DTH）相关（CD4 + r = 0.63（p = 0.002），CD8 + r = 0.47（p = 0.03）），表明它们代表T细胞记忆回忆反应。对4xCP肽的增殖性CD8+以及可能的CD4 +亚群反应与Vacc-4x相关（分别为r = 0.46（p = 0.03）和r = 0.38（p = 0.08））。41%的患者仍有Vacc-4x特异性IFN + CD4 + T细胞，这与4xCP肽的相应频率相关（r = 0.50，p = 0.02）。55%的患者发现了针对Vacc-4x的CD107a（+）IFN（+）CD8 + T细胞反应。
对于HIV感染患者，基于肽的免疫治疗候选物具有持久T细胞记忆回忆反应的证据应增强对基于肽的皮内疫苗递送的关注。
