Safety and Immunogenicity of a PD-1-Enhanced HIV-1 Therapeutic DNA Vaccine: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Clinical Trial in People With HIV-1 on Antiretroviral Therapy

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ID: 320918
2026
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Abstract
BACKGROUND: Therapeutic vaccines represent a potential strategy for HIV-1 control without antiretroviral therapy (ART). We report a first-in-human study on ICVAX™, a PD-1-enhanced HIV-1 therapeutic DNA vaccine. METHODS: This NMPA-approved, randomized, double-blind, placebo-controlled, dose-escalation phase I trial (NCT06253533) was conducted at Shenzhen Third People's Hospital, China. Adults with HIV-1 aged 18-50 years on ART were sequentially allocated to 1, 2, or 4 mg dose groups of 15, each randomized 12:3 to ICVAX or placebo. Participants received intramuscular injections with electroporation at Weeks 0, 4, 8, 12, and 36. Primary safety, secondary immunological, and exploratory virological outcomes were recorded. RESULTS: All 45 participants completed the trial, with 12 per ICVAX cohort and 9 in pooled Placebo. Treatment-related adverse events occurred in 100% of placebo and 83.3% of ICVAX recipients, all mild and transient, predominantly local reactions. A ≥2-fold increase of peak ELISpot T-cell responses over baseline was achieved by 75%, 75%, and 58.3% of low-dose, mid-dose, and high-dose recipients, versus 33.3% for Placebo. ICVAX recipients also showed low-frequency Gag-specific T cells expressing CD107a and/or effector cytokines. CONCLUSIONS: ICVAX was well-tolerated and elicited robust antigen-specific T-cell responses in ART-suppressed people with HIV-1. Its efficacy will be assessed in future studies.
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Authors Qiaoli Peng, Yik Chun Wong, Wing Yin Cheng, Yun He, Chengxi Xie, Yirong Shi, Ting Wang, Yanhua Du, Xiaoyun Yang, Zhongfang Wang, Hui Wang, Hongzhou Lu, Zhiwei Chen, Xia Jin
Journal The Journal of infectious diseases
Year 2026
DOI
10.1093/infdis/jiag320
URL
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