title: Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes: safety, immunogenicity, and feasibility in Guinea-Bissau.
abstract: We have designed a therapeutic HIV-1 vaccine concept based on peptides together with the adjuvant CAF01. Peptides represented 15 HLA-supertype-restricted subdominant and conserved CD8 T cell epitopes and three CD4 T-helper cell epitopes. In this phase I clinical trial, safety and immunogenicity were assessed in untreated HIV-1-infected individuals in Guinea-Bissau, West Africa. Twenty-three HIV-1-infected individuals were randomized to receive placebo (n=5) or vaccine (n=18). Safety was appraised by clinical follow-up combined with monitoring of biochemistry, hematology, CD4 T cell counts, and HIV-1 viral loads. T cell immunogenicity was monitored longitudinally by interferon (IFN)-γ ELISpot. New vaccine-specific T cell responses were induced in 6/14 vaccinees for whom ELISpot data were valid. CD4 T cell counts and viral loads were stable. The study shows that therapeutic immunization is feasible and safe in Guinea-Bissau and that it is possible to redirect T cell immunity with CAF01-adjuvanted HIV-1 peptide vaccine during untreated HIV-1 infection in some patients. However, relatively few preexisting and vaccine-induced HIV-1 T cell responses to CD8 T cell epitopes were detected against HIV-1 using IFN-γ ELISpot in this chronically infected African population.
authors: 1 Department of Virology, Statens Serum Institut , Copenhagen, Denmark .
authors: Victor Raúl Gómez
authors: VR
authors: Román
authors: Kristoffer Jarlov
authors: KJ
authors: Jensen
authors: Sanne Skov
authors: SS
authors: Jensen
authors: Christian
authors: C
authors: Leo-Hansen
authors: Sanne
authors: S
authors: Jespersen
authors: David
authors: D
authors: da Silva Té
authors: Candida Medina
authors: CM
authors: Rodrigues
authors: Christoph Mikkel
authors: CM
authors: Janitzek
authors: Lasse
authors: L
authors: Vinner
authors: Terese Lea
authors: TL
authors: Katzenstein
authors: Peter
authors: P
authors: Andersen
authors: Ingrid
authors: I
authors: Kromann
authors: Lars Vibe
authors: LV
authors: Andreasen
authors: Ingrid
authors: I
authors: Karlsson
authors: Anders
authors: A
authors: Fomsgaard
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D006169:Guinea-Bissau; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D019562:Viral Load; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; C574674:La protein, human; D008081:Liposomes; D010750:Phosphoproteins; D007371:Interferon-gamma