Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection.

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the "cold chain" is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.

Interleukin-23: immunological roles and clinical implications.

Increasing evidence has revealed the importance of IL-23, which closely resembles IL-12 both structurally and immunologically, in linking innate and adaptive immunity. IL-23, produced by activated type 1 macrophages and dendritic cells (DC), possesses unique roles in the differentiation and expansion of memory T cells. IL-23 has been associated with several inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (IBD) and Helicobacter pylori associated gastritis, mainly due to its capacity to induce a strong Th1 type immune response. IL-23 is also associated with Th17 responses and the cytokine produced by the antigen presenting cells (APC), i.e. IL-12 vs IL-23 determines in part if a response is Th1 or Th17. Recent studies have also associated chronic inflammatory diseases such as IBD, psoriasis and myocardial infarction with polymorphisms of the IL-23 receptor complex. The current review focuses on the immunological role of IL-23 and possible therapeutic avenues for inflammatory diseases.