title: A double-blind randomized phase I clinical trial targeting ALVAC-HIV vaccine to human dendritic cells.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00013572.
authors.affiliation: U.S. Military HIV Research Program, Rockville, Maryland, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eller
authors.forename: Bonnie M
authors.initials: BM
authors.lastname: Slike
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Cox
authors.forename: Emil
authors.initials: E
authors.lastname: Lesho
authors.forename: Zhining
authors.initials: Z
authors.lastname: Wang
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Currier
authors.forename: Janice M
authors.initials: JM
authors.lastname: Darden
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Maryanne T
authors.initials: MT
authors.lastname: Vahey
authors.forename: Sheila
authors.initials: S
authors.lastname: Peel
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Mary A
authors.initials: MA
authors.lastname: Marovich
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000328:Adult; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D010865:Pilot Projects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; C078788:ALVAC vaccine; D016207:Cytokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007074:Immunoglobulin G; D014765:Viral Vaccines