通过 DNA 疫苗接种聚焦于 HIV-1 Gag T 细胞对高度保守区域的反应，该研究在 HVTN 119 中进行。

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119.

机构信息

Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USA.

出版信息

JCI Insight. 2024 Aug 1;9(18):e180819. doi: 10.1172/jci.insight.180819.

BACKGROUNDAn HIV-1 DNA vaccine composed of 7 highly conserved, structurally important elements (conserved elements, CE) of p24Gag was tested in a phase I randomized, double-blind clinical trial (HVTN 119, NCT03181789) in people without HIV. DNA vaccination of CE prime/CE+p55Gag boost was compared with p55Gag.METHODSTwo groups (n = 25) received 4 DNA vaccinations (CE/CE+p55Gag or p55Gag) by intramuscular injection/electroporation, including IL-12 DNA adjuvant. The placebo group (n = 6) received saline. Participants were followed for safety and tolerability. Immunogenicity was assessed for T cell and antibody responses.RESULTSBoth regimens were safe and generally well tolerated. The p24CE vaccine was immunogenic and significantly boosted by CE+p55Gag (64% CD4+, P = 0.037; 42% CD8+, P = 0.004). CE+p55Gag induced responses to 5 of 7 CE, compared with only 2 CE by p55Gag DNA, with a higher response to CE5 in 30% of individuals (P = 0.006). CE+p55Gag induced significantly higher CD4+ CE T cell breadth (0.68 vs. 0.22 CE; P = 0.029) and a strong trend for overall T cell breadth (1.14 vs. 0.52 CE; P = 0.051). Both groups developed high cellular and humoral responses. p24CE vaccine-induced CD4+ CE T cell responses correlated (P = 0.007) with p24Gag antibody responses.CONCLUSIONThe CE/CE+p55Gag DNA vaccine induced T cell responses to conserved regions in p24Gag, increasing breadth and epitope recognition throughout p55Gag compared with p55Gag DNA. Vaccines focusing immune responses by priming responses to highly conserved regions could be part of a comprehensive HIV vaccine strategy.TRIAL REGISTRATIONClinical Trials.gov NCT03181789FUNDINGHVTN, NIAID/NIH.

背景

一种由 HIV-1 包膜 p24Gag 的 7 个高度保守、结构重要的元件（保守元件，CE）组成的 DNA 疫苗，在未感染 HIV 的人群中进行了 I 期随机、双盲临床试验（HVTN 119，NCT03181789）的测试。CE 初免/CE+p55Gag 加强免疫与 p55Gag 进行了比较。

方法

两组（n=25）通过肌肉内注射/电穿孔接受 4 次 DNA 疫苗（CE/CE+p55Gag 或 p55Gag），包括 IL-12 DNA 佐剂。安慰剂组（n=6）接受生理盐水。对参与者进行安全性和耐受性随访。评估 T 细胞和抗体反应的免疫原性。

结果

两种方案均安全且通常耐受良好。p24CE 疫苗具有免疫原性，CE+p55Gag 可显著增强其免疫原性（64% CD4+，P=0.037；42% CD8+，P=0.004）。CE+p55Gag 诱导对 7 个 CE 中的 5 个产生反应，而 p55Gag DNA 仅对 2 个 CE 产生反应，在 30%的个体中对 CE5 的反应更高（P=0.006）。CE+p55Gag 诱导的 CD4+CE T 细胞广度显著更高（0.68 比 0.22 CE；P=0.029），整体 T 细胞广度呈强趋势（1.14 比 0.52 CE；P=0.051）。两组均产生了高细胞和体液反应。p24CE 疫苗诱导的 CD4+CE T 细胞反应与 p24Gag 抗体反应相关（P=0.007）。