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ABSTRACT: Background
To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig).Methods
This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4), or adjuvant given 2 days after vaccine (group T5).Results
No significant differences in adverse events were observed between treatment groups. Cellular immune responses to envelope protein EnvA peptides were detected by interferon (IFN) γ and IL-2 enzyme-linked immunospot (ELISPOT) assays in 50% and 40% of subjects, respectively, in T4, and in 100% and 80% in T5. The median responses for groups T4 and T5, respectively, were 90 and 193 spot-forming cells (SFCs)/10⁶ peripheral blood mononuclear cells (P = .004; T4 vs T5) for the IL-2 ELISPOT assay and 103 and 380 SFCs/10⁶ PBMCs (P = .003; T4 vs T5) for the IFN-γ ELISPOT assay. A trend to more durable cellular immune responses in T5 was observed at 1 year (T5 vs T4/D; P = .07). Higher anti-Env antibody responses were detected with T5 than with T4.Conclusions
Plasmid IL-2/Ig significantly increased immune responses when administered 2 days after the DNA vaccine, compared with simultaneous administration. These observations have important implications for the development of cytokine augmentation strategies.Clinical trials registration
NCT00069030.
SUBMITTER: Baden LR
PROVIDER: S-EPMC3222108 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Baden Lindsey R LR Blattner William A WA Morgan Cecilia C Huang Yunda Y Defawe Olivier D OD Sobieszczyk Magdalena E ME Kochar Nidhi N Tomaras Georgia D GD McElrath M Juliana MJ Russell Nina N Brandariz Kara K Cardinali Massimo M Graham Barney S BS Barouch Dan H DH Dolin Raphael R
The Journal of infectious diseases 20110921 10
<h4>Background</h4>To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig).<h4>Methods</h4>This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing do ...[more]