title: IMP321 (sLAG-3) safety and T cell response potentiation using an influenza vaccine as a model antigen: a single-blind phase I study.
abstract: sLAG-3 (IMP321), a natural high affinity ligand for MHC class II, was tested for safety, tolerability and its ability to increase Th-1-type T cell responses to a commercial trivalent split influenza vaccine (Agrippal) in a phase I single-blinded, randomized, controlled clinical trial. Twenty healthy volunteers were first injected with increasing doses of IMP321 alone (safety for first-in-man use). Then 40 volunteers were recruited into 4 consecutive cohorts of 10 subjects, who were randomly assigned to receive the flu vaccine plus 3, 10, 30 or 100 microg IMP321 or the flu vaccine plus saline control. All vaccine formulations were found to be generally well tolerated with similar frequency and intensity of adverse reaction in groups receiving IMP321 as in controls. Post-vaccination humoral immune responses, as determined 29 and 57 days later by assay of hemagglutinin inhibition activity were similar for both IMP321 and control groups. In contrast, the addition of 10, 30 or 100 microg IMP321 to the flu vaccine resulted in higher levels of Th1-type (IFN-gamma, TNF-alpha or IL-2) flu-specific CD4 T cells in PBMC recovered at D29 and D57 and tested in a short-term ex vivo restimulation assay (6-colour FACS analysis after intra-cellular staining of cytokines). In summary, IMP321 as an adjuvant to a model antigen (Agrippal) was well-tolerated and may enhance T cell response vaccine immunogenicity.
authors.affiliation: Immutep SA, Parc Club Orsay, 2 rue Jean Rostand, Orsay, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Brignone
authors.forename: Caroline
authors.initials: C
authors.lastname: Grygar
authors.forename: Manon
authors.initials: M
authors.lastname: Marcu
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Perrin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Triebel
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear; D008297:Male; D016037:Single-Blind Method; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015703:Antigens, CD; D007252:Influenza Vaccines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human; C000720328:soluble LAG-3 protein, human