title: A randomized, placebo-controlled trial of subcutaneous administration of GM-CSF as a vaccine adjuvant: effect on cellular and humoral immune responses.
abstract: Thirty healthy volunteers were randomly assigned to receive either a single subcutaneous injection of GM-CSF or placebo at the time of vaccination with tetanus and diptheria toxoid (Td), influenza and hepatitis A vaccines. Humoral response was measured by weekly serum samples assayed for antibodies to tetanus toxoid (TT), influenza and hepatitis A; while cellular response to TT was determined by measuring IL-2 expression in T-cells following in vitro exposure to TT antigen using a flow cytometric assay. It was hypothesized that (1). GM-CSF would augment immune response and (2). that the frequencies of TT responsive T-cells in the blood would predict humoral responses. The administration of subcutaneous GM-CSF as an adjuvant at the time of vaccination did not augment the antibody responses to influenza or hepatitis A in normal volunteers when compared to placebo. Subjects who received GM-CSF had statistically significant lower increases in anti-tetanus antibodies than placebo recipients. Immunization with TT resulted in an increase in the frequency of antigen responsive T-cells in the blood over time. The frequencies of TT responsive T-cells in baseline blood samples were correlated with baseline anti-tetanus antibody titers, but humoral and cellular responses were not correlated following vaccination. Recipients of GM-CSF did not develop significantly higher numbers of TT responsive T-cells after vaccination compared to recipients who received placebo.
authors.affiliation: Department of Medicine, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA. jsomani@emory.edu
authors.forename: Jyoti
authors.initials: J
authors.lastname: Somani
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Hilary
authors.initials: H
authors.lastname: Rosenthal
authors.forename: Suzanne
authors.initials: S
authors.lastname: Resnick
authors.forename: Irina
authors.initials: I
authors.lastname: Kakhniashvili
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000917:Antibody Formation / Q000276:immunology*; D022422:Diphtheria-Tetanus Vaccine; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000276:immunology; D022362:Hepatitis A Vaccines; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007279:Injections, Subcutaneous; D008297:Male; D013745:Tetanus Toxoid / Q000276:immunology; D014611:Vaccination; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D022422:Diphtheria-Tetanus Vaccine; D022362:Hepatitis A Vaccines; D007252:Influenza Vaccines; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D016178:Granulocyte-Macrophage Colony-Stimulating Factor