Therapeutic DNA Vaccination of Vertically HIV-Infected Children: Report of the First Pediatric Randomised Trial (PEDVAC)

Paolo Palma,Hyppolite K Tchidjou,Marco Montano,Britta Wahren,Lars E Eriksson,Angela Aquilani,Stefania Dispinseri,Carla Montesano,Paolo Rossi,Nadia Mora,Stefania Bernardi,Maria Luisa Romiti,Stefania Baldassari,Gabriella Scarlatti,Veronica Santilli,Sarah Pett

doi:10.1371/journal.pone.0079957

Abstract

SubjectsTwenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3.InterventionTen 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.ResultsSafety 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.ConclusionsThe 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 _2007-002359-18 IT

Highlights

Current antiretroviral therapy (ART) recommended for the HIV-infected pediatric population requires medication early, daily and indefinitely [1]
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, reverse transcriptase (RT) or Env did not reach significance
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)

Summary

Introduction

Current antiretroviral therapy (ART) recommended for the HIV-infected pediatric population requires medication early, daily and indefinitely [1]. Recent data clearly show that vertically HIV-infected children have a progressively increased risk of developing triple-class virological failure after 5 years on highly active ART [2]. New therapeutic strategies are necessary for the pediatric population, as these children approach adolescence. T-cell induced HIV viral modifications have been reported with an adenovirus-based prophylactic HIV vaccine in the STEP trial [4]. These data demonstrate the possibility of exerting selective viral pressure with a vaccine strategy. We report data from the PEDVAC trial, which is the first study of an HIVDNA therapeutic vaccine in vertically infected children

Objectives

Methods

Results

Conclusion