Regulation of innate and adaptive immune responses by synthetic and pathogen-derived immunomodulatory molecules

Abstract

The development of new and improved vaccine formulations for human use requires the discovery of efficacious non-toxic adjuvants that enhance immune responses to poorly immunogenic purified native or recombinant antigens. In addition, the route of vaccination may be an important factor in the generation of protective immunity against pathogens that infect the body through mucosal routes. Mucosal immunisation is a favoured alternative to conventional parenteral routes, as it dispenses with the use of needles, is easier to administer and allows the induction of local as well as systemic immunity. In this study, three novel peptides/proteins from Mycobacterium tuberculosis, HIV and Plasmodium falciparum formulated with mutant bacterial toxins, CTA1-DD or LTK63, as adjuvants with chitosan as a delivery vehicle were evaluated for their ability to generate antigen-specific cell-mediated and humoral immune responses following nasal immunisation. Intranasal immunisation with the peptides/proteins in the absence of adjuvant generated weak Th cell responses. However, formulation with LTK63 and chitosan enhanced antigenspecific Th1 responses to the nasally administered antigens. In addition, the combination of CTA1-DD with chitosan enhanced the generation of antigen-specific IgG antibodies. The results suggest that immune responses can be generated with poorly immunogenic antigens by the nasal route, using a combination of non-toxic mucosal adjuvants and an appropriate antigen delivery system.