Therapeutic DNA vaccination of vertically HIV-infected children: report of the first pediatric randomised trial (PEDVAC)

PLoS One. 2013 Nov 28;8(11):e79957. doi: 10.1371/journal.pone.0079957. eCollection 2013.

Abstract

Subjects: Twenty vertically HIV-infected children, 6-16 years of age, with stable viral load control and CD4+ values above 400 cells/mm(3).

Intervention: Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96.

Results: Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A.

Conclusions: The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population.

Trial registration: clinicaltrialsregister.eu _2007-002359-18IT.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / adverse effects
  • AIDS Vaccines / immunology
  • AIDS Vaccines / therapeutic use*
  • Adolescent
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • Child
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / therapy*
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / immunology
  • Humans
  • Infectious Disease Transmission, Vertical*
  • Male
  • Treatment Outcome
  • Vaccination
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use*
  • Viral Load

Substances

  • AIDS Vaccines
  • Vaccines, DNA

Grants and funding

This work was supported by grants from the Swedish Research Council and the FP6 European Union Europrise network of excellence for the development of HIV vaccine and microbicides (grant 037611) and by the Italian Ministry of Health, Rome (Finalized Project 2011); Italian Health Institute, Rome (AIDS 40H91- ISS/OPBG). The reagents ARP631 Rec HIV-1 RT, ARP694 HIV p17/24 Clade B, ARP695 HIV-1 p17/24 C Clade, ARP698 HIV-1 UG37 gp140 Clade A, ARP699 CN54 gp140 Clade C, ARP680 Rec HIV-1 rgp41 and EVA620 HIV-1 p24 Clade B were provided by the Centre for AIDS Reagents, NIBSC, UK, Programme EVA supported by the European Community by FP6/7 Europrise Network of Excellence, AVIP and NGIN consortia and the Bill and Melinda Gates GHRC-CAVD Project and were donated by Dr. D. Stammers, GLAXO, Welcome (ARP631), FIT BIOTECH Oyj Plc Eesti Filiaal, TARTU, ESTONIA (ARP694 and ARP695), Polymun, Vienna, Austria (ARP698 and ARP699), Immunogenetics Inc. (EVA620). SD and PP were supported by the FP6 European Union Europrise network of excellence. This is a non-profit study, and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.