Dissecting the components of the humoral immune response elicited by DNA vaccines

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. (c) 2005 Elsevier Ltd. All rights reserved.