Immunotherapy with an HIV-DNA Vaccine in Children and Adults.
Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals' immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children's and adults' responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4-16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected.
University Department of Pediatrics (DPUO), Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. paolo.palma@opbg.net.|Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. paolo.palma@opbg.net.
Paolo
P
Palma
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden. Lindvi.Gudmundsdotter@affibody.se.|Affibody AB, 17163 Solna, Sweden. Lindvi.Gudmundsdotter@affibody.se.
Lindvi
L
Gudmundsdotter
University Department of Pediatrics (DPUO), Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. andrea.finocchi@opbg.net.|Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. andrea.finocchi@opbg.net.
Andrea
A
Finocchi
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge 171 77, Sweden. Lars.Eriksson@ki.se.|Department of Infectious Diseases, Karolinska University Hospital, Stockholm 171 77, Sweden. Lars.Eriksson@ki.se.|School of Health Sciences, City University London, London EC1V 0HB, UK. Lars.Eriksson@ki.se.
Lars E
LE
Eriksson
Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
Nadia
N
Mora
Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. veronica.santilli@hotmail.it.
Veronica
V
Santilli
Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. angela.aquilani@libero.it.
Angela
A
Aquilani
Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. emma_m@hotmail.it.
Emma C
EC
Manno
Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. paolazangari@hotmail.com.
Paola
P
Zangari
Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. romiti@med.uniroma2.it.
Maria Luisa
ML
Romiti
Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy. montesano@uniroma2.it.
Carla
C
Montesano
Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy. alba.grifoni@uniroma2.it.
Alba
A
Grifoni
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden. andreas.brave@folkhalsomyndigheten.se.
Andreas
A
Brave
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden. karl.ljungberg@ki.se.
Karl
K
Ljungberg
Vecura, Clinical Research Center, Karolinska University Hospital, Stockholm 141 86, Sweden. pontus.blomberg@karolinska.se.
Pontus
P
Blomberg
University Department of Pediatrics (DPUO), Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. stefania.bernardi@opbg.net.
Stefania
S
Bernardi
Venhälsan, Karolinska Institutet (KI), Södersjukhuset, Stockholm 118 83, Sweden.
Eric
E
Sandström
Venhälsan, Karolinska Institutet (KI), Södersjukhuset, Stockholm 118 83, Sweden.
Bo
B
Hejdeman
University Department of Pediatrics (DPUO), Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy. paolo.rossi@opbg.net.|Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. paolo.rossi@opbg.net.
Paolo
P
Rossi
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden. Britta.Wahren@ki.se.
Britta
B
Wahren
DNA vaccine; HIV-1; children and adults