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A double-blind randomized phase I clinical trial targeting ALVAC-HIV vaccine to human dendritic cells.
A double-blind randomized phase I clinical trial targeting ALVAC-HIV vaccine to human dendritic cells.
- Source :
-
PloS one [PLoS One] 2011; Vol. 6 (9), pp. e24254. Date of Electronic Publication: 2011 Sep 16. - Publication Year :
- 2011
-
Abstract
- 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.<br />Methodology/principal Findings: Healthy HIV-1 uninfected volunteers were administered ALVAC-HIV or placebo by intramuscular injection (i.m.), intradermal injection (i.d.) or subcutaneous injection (s.q.) 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 i.m. 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.<br />Conclusions/significance: ALVAC-HIV delivered i.m., i.d. or s.q. 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.<br />Trial Registration: ClinicalTrials.gov NCT00013572.
- Subjects :
- AIDS Vaccines administration & dosage
Adult
Cytokines blood
Cytokines immunology
Dendritic Cells metabolism
Dendritic Cells transplantation
Double-Blind Method
Enzyme-Linked Immunosorbent Assay
Female
Gene Expression immunology
Gene Expression Profiling
HIV Antibodies blood
HIV Antibodies immunology
HIV Envelope Protein gp120 immunology
HIV Envelope Protein gp160 immunology
HIV Infections prevention & control
Humans
Immunoglobulin G blood
Immunoglobulin G immunology
Injections, Intradermal
Injections, Intramuscular
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Male
Pilot Projects
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic metabolism
Time Factors
Viral Vaccines immunology
AIDS Vaccines immunology
Dendritic Cells immunology
HIV Infections immunology
HIV-1 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21949699
- Full Text :
- https://doi.org/10.1371/journal.pone.0024254