Immunotherapy with an HIV-DNA Vaccine in Children and Adults

Vaccines

Paolo Palma²  Lindvi Gudmundsdotter³  Andrea Finocchi²  Lars E. Eriksson⁷  Nadia Mora¹  Veronica Santilli¹  Angela Aquilani¹  Emma C. Manno¹  Paola Zangari¹  Maria Luisa Romiti¹  Carla Montesano⁵  Alba Grifoni⁵  Andreas Brave³  Karl Ljungberg³  Pontus Blomberg⁶  Stefania Bernardi²  Eric Sandström⁴  Bo Hejdeman⁴  Paolo Rossi² 

[1] Chair of Pediatrics, Department of System Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; E-Mails:;University Department of Pediatrics (DPUO), Unit of Immune and Infectious Diseases, Children’s Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy; E-Mails:;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden; E-Mails:;Venhälsan, Karolinska Institutet (KI), Södersjukhuset, Stockholm 118 83, Sweden; E-Mails:;Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy; E-Mails:;Vecura, Clinical Research Center, Karolinska University Hospital, Stockholm 141 86, Sweden; E-Mail:;Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge 171 77, Sweden; E-Mail:

关键词: HIV-1;    DNA vaccine;    children and adults;   

DOI  :  10.3390/vaccines2030563

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.