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PLoS One. 2012;7(1):e29231. doi: 10.1371/journal.pone.0029231. Epub 2012 Jan 5.

Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults.

Author information

1
Division of Infectious Diseases, Department of Medicine, Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of Ameica. s.kalams@vanderbilt.edu

Abstract

BACKGROUND:

DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques.

METHODOLOGY/PRINCIPAL FINDINGS:

We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response.

CONCLUSIONS/SIGNIFICANCE:

This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT00115960 NCT00111605.

PMID:
22242162
PMCID:
PMC3252307
DOI:
10.1371/journal.pone.0029231
[Indexed for MEDLINE]
Free PMC Article

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