Dendritic cell discoveries provide new insight into the cellular immunobiology of DNA vaccines

The evolution of increasingly virulent human pathogens, together with the r apid onset of antimicrobial resistance has created a need for new vaccinati on strategies. Nucleic acid vaccines, based on recombinant DNA technology a re a promising new vaccine formulation capable of eliciting both humoral an d cellular immune responses. This technology has been experimentally valida ted in animal models of pathogen challenge and tumor protection following a dministration of a DNA vaccine and has led to extensive research into the m echanisms of protective immunity. We focus here on the cellular and molecul ar mechanisms leading to cell-mediated immune responses to DNA vaccines and discuss these mechanisms in light of recent advances in the field of dendr itic cell immunobiology. In particular, the potential involvement of. (i) t he CpG pattern-recognition receptor, toll-like receptor-9; (ii) the dendrit ic cell-specific surface adhesion molecule, DC-SIGN; and (iii) the molecula r interactions between CD40 and CD154 in the evolution of protective cell-m ediated immunity to DNA vaccines are discussed. An improved understanding o f the precise mechanisms leading to protective cellular immunity following DNA vaccination may help in the design of novel DNA constructs containing i mmunostimulatory features that target one or more of these mechanisms, with the aim of increasing the immunogenic potential and protective efficacy of DNA vaccines. (C) 2001 Elsevier Science B.V. All rights reserved.