title: Dissecting the components of the humoral immune response elicited by DNA vaccines.
abstract: Although DNA vaccines appear to be efficient at inducing strong cellular immune responses, a number of questions remain regarding their ability to induce humoral immunity. The essential components for generating an antibody response include B and T cell recognition of antigen, subsequent activation, clonal expansion of each lymphocyte type and migration of T cells into B cell follicles to provide help, all leading to germinal centre formation and antibody production. We have employed a double adoptive transfer system based on ovalbumin (OVA)-specific CD4+ DO11.10 T cells and hen egg lysozyme (HEL)-specific MD4 B cells to assess all of these parameters in the context of DNA vaccination in vivo. We find that vaccination with DNA constructs expressing an OVA-HEL gene fusion (encoding contiguous T and B cell epitopes) can induce T cell activation, clonal expansion and migration into B cell follicles accompanied by B cell activation, blastogenesis, expansion and antibody production. These findings show that DNA vaccination can induce all of the components required for humoral immunity and also provide a system for in depth analysis of factors that influence the development of antibody responses. Such strategies may facilitate the rational design of vaccines capable of inducing effective humoral immunity.
authors.affiliation: Division of Immunology, Infection and Inflammation, Western Infirmary, University of Glasgow, Glasgow G116NT, UK. C.Rush@clinmed.gla.ac.uk
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Rush
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchell
authors.forename: Bernard
authors.initials: B
authors.lastname: Burke
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D019444:Vaccines, DNA