CD40-expressing plasmid induces anti-CD40 antibody and enhances immune responses to DNA vaccination.

BACKGROUND

Various approaches have been used to improve the efficacy of DNA vaccination, including the incorporation of molecular adjuvants. Because the CD40 ligand-CD40 interaction plays a major role in initiating immune responses, we sought to develop a molecular adjuvant targeting this interaction.

METHODS AND RESULTS

We immunized mice with a foot-and-mouth disease virus DNA vaccine, pcD-VP1, together with a CD40-expressing plasmid, pcD-CD40. We found that pcD-CD40 induced anti-CD40 antibodies, which temporally correlated with the augmented production of anti-VP1 antibody. pcD-CD40 similarly augmented the humoral response of another DNA vaccine that targets hepatitis B virus, and passive transfer of anti-CD40 antisera also showed a similar effect. Furthermore, the pcD-CD40-elicited anti-CD40 antibodies were able to activate the CD40 signal pathway in antigen-presenting cells in vitro, which led to the maturation of dendritic cells (DCs) and DC-mediated T cell activation. Thus, pcD-CD40 augments DNA vaccination by inducing anti-CD40 antibodies, which in turn promotes T cell activation.

CONCLUSIONS

This is the first reported 'proadjuvant' that augments DNA vaccination indirectly by eliciting agonistic antibodies.