A Double-Blind Randomized Phase I Clinical Trial Targeting ALVAC-HIV Vaccine to Human Dendritic CellsReport as inadecuate




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Background

We conducted a novel pilot study comparing different delivery routes of ALVAC-HIV vCP205, a canarypox vaccine containing HIV gene inserts: env, gag and pol. We explored the concept that direct ex vivo targeting of human dendritic cells DC would enhance the immune response compared to either conventional intramuscular or intradermal injections of the vaccine alone.

Methodology-Principal Findings

Healthy HIV-1 uninfected volunteers were administered ALVAC-HIV or placebo by intramuscular injection IM, intradermal injection ID or subcutaneous injection SQ of autologous ex vivo transfected DC at months 0, 1, 3 and 6. All vaccine delivery routes were well tolerated. Binding antibodies were observed to both the ALVAC vector and HIV-1 gp160 proteins. Modest cellular responses were observed in 2-7 individuals in the DC arm and 1-8 in the IM arm as determined by IFN-γ ELISPOT. Proliferative responses were most frequent in the DC arm where 4-7 individuals had measurable responses to multiple HIV-1 antigens. Loading DC after maturation resulted in lower gene expression, but overall better responses to both HIV-1 and control antigens, and were associated with better IL-2, TNF-α and IFN-γ production.

Conclusions-Significance

ALVAC-HIV delivered IM, ID or SQ with autologous ex vivo transfected DC proved to be safe. The DC arm was most immunogenic. Proliferative immune responses were readily detected with only modest cytotoxic CD8 T cell responses. Loading mature DC with the live viral vaccine induced stronger immune responses than loading immature DC, despite increased transgene expression with the latter approach. Volunteers who received the autologous vaccine loaded mature DC developed a broader and durable immune response compared to those vaccinated by conventional routes.

Trial Registration

ClinicalTrials.gov NCT00013572



Author: Michael A. Eller , Bonnie M. Slike , Josephine H. Cox, Emil Lesho, Zhining Wang, Jeffrey R. Currier, Janice M. Darden, Victoria R

Source: http://plos.srce.hr/



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