Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
JCI Insight. 2020 Jul 9;5(13):137079. doi: 10.1172/jci.insight.137079.
BACKGROUNDHVTN 098, a randomized, double-blind, placebo-controlled trial, evaluated the safety, tolerability, and immunogenicity of PENNVAX-GP HIV DNA vaccine, administered with or without plasmid IL-12 (pIL-12), via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, HIV-uninfected adults. The study tested whether PENNVAX-GP delivered via ID/EP at one-fifth the dose could elicit equivalent immune responses to delivery via IM/EP and whether inclusion of pIL-12 provided additional benefit.METHODSParticipants received DNA encoding HIV-1 env/gag/pol in 3 groups: 1.6 mg ID (ID no IL-12 group, n = 20), 1.6 mg ID + 0.4 mg pIL-12 (ID + IL-12 group, n = 30), 8 mg IM + 1 mg pIL-12 (IM + IL-12 group, n = 30), or placebo (n = 9) via EP at 0, 1, 3, and 6 months. Results of cellular and humoral immunogenicity assessments are reported.RESULTSFollowing vaccination, the frequency of responders (response rate) to any HIV protein based on CD4+ T cells expressing IFN-γ or IL-2 was 96% for both the ID + IL-12 and IM + IL-12 groups; CD8+ T cell response rates were 64% and 44%, respectively. For ID delivery, the inclusion of pIL-12 increased CD4+ T cell response rate from 56% to 96%. The frequency of responders was similar (≥90%) for IgG binding antibody to gp140 consensus Env across all groups, but the magnitude was higher in the ID + IL-12 group compared with the IM + IL-12 group.CONCLUSIONPENNVAX-GP DNA induced robust cellular and humoral immune responses, demonstrating that immunogenicity of DNA vaccines can be enhanced by EP route and inclusion of pIL-12. ID/EP was dose sparing, inducing equivalent, or in some aspects superior, immune responses compared with IM/EP.TRIAL REGISTRATIONClinicalTrials.gov NCT02431767.FUNDINGThis work was supported by National Institute of Allergy and Infectious Diseases (NIAID), U.S. Public Health Service grants, an HIV Vaccine Design and Development Team contract, Integrated Preclinical/Clinical AIDS Vaccine Development Program, and an NIH award.
HVTN 098 是一项随机、双盲、安慰剂对照试验，评估了 PENNVAX-GP HIV DNA 疫苗在健康、未感染 HIV 的成年人中的安全性、耐受性和免疫原性，该疫苗通过皮内（ID）或肌肉内（IM）电穿孔（EP）给予，同时给予或不给予质粒 IL-12（pIL-12）。该研究测试了 PENNVAX-GP 通过 ID/EP 以五分之一的剂量给药是否可以引起与 IM/EP 给药相当的免疫反应，以及包含 pIL-12 是否可以提供额外的益处。
参与者分 3 组接受编码 HIV-1 env/gag/pol 的 DNA：1.6mg ID（无 ID IL-12 组，n=20）、1.6mg ID+0.4mg pIL-12（ID+IL-12 组，n=30）、8mg IM+1mg pIL-12（IM+IL-12 组，n=30）或安慰剂（n=9）通过 EP 在 0、1、3 和 6 个月时给药。报告了细胞和体液免疫原性评估的结果。
接种疫苗后，基于表达 IFN-γ或 IL-2 的 CD4+T 细胞对任何 HIV 蛋白的应答者（应答率）在 ID+IL-12 和 IM+IL-12 组中均为 96%；CD8+T 细胞应答率分别为 64%和 44%。对于 ID 给药，包含 pIL-12 可将 CD4+T 细胞应答率从 56%提高至 96%。各组对 gp140 共识 Env 的 IgG 结合抗体的应答者频率均相似（≥90%），但 ID+IL-12 组的应答者频率高于 IM+IL-12 组。
PENNVAX-GP DNA 诱导了强烈的细胞和体液免疫应答，表明 DNA 疫苗的免疫原性可以通过 EP 途径和包含 pIL-12 来增强。ID/EP 具有节省剂量的作用，与 IM/EP 相比，可诱导等效或在某些方面更优的免疫应答。
ClinicalTrials.gov NCT02431767。
本工作得到美国国立过敏和传染病研究所（NIAID）、美国公共卫生服务拨款、HIV 疫苗设计和开发团队合同、综合临床前/艾滋病疫苗开发计划以及 NIH 奖的支持。
