Nexvax2
Nexpep worked under a collaborative agreement with The Walter and Eliza Hall Institute in Melbourne, Australia, to fully dissect the immune reaction to gluten in coeliac disease. Based upon this ground-breaking research, Nexpep has developed the peptide-based therapeutic vaccine, Nexvax2. Nexpep has completed preclinical development of Nexvax2, and has commenced clinical trials to test the effects of Nexvax2 in patients with coeliac disease.
Nexvax2 evolved from studies in patients with coeliac disease who had oral gluten challenge to reactivate the gluten immune response. (ref. 9, 10) This approach avoids many artifacts and uncertainties in interpreting results which may be caused by prolonged manipulation of cells and tissue in the laboratory, and in basing drug design on animal models.
Nexvax2 is one of an emerging class of therapeutic vaccines based on the same principles as “traditional” desensitisation therapy for allergic conditions using whole proteins (ref. 4, 5).
Peptides derived from gluten and mostly modified by the intestinal enzyme, tissue transglutaminase, bound to HLA DQ2 (present in 90% of patients with coeliac disease) are recognised by T cells and control the immune reaction to gluten (ref. 6–8).
Controlled reactivation of coeliac disease with short-term oral gluten challenge induces T cells in blood which have been used to select the gluten peptides recognised by the most T cells in the most patients (ref 9–11).
Nexvax2 encompasses peptides that account for a substantial proportion of the T-cell reaction to gluten in patients with HLA DQ2-associated coeliac disease. Nexpep has converted these peptides into a pharmaceutical agent capable of inducing immune tolerance in a rodent model of HLA DQ2-restritced T-cell immunity to gluten.
Peptide-based therapeutic vaccines have been successful in preventing and treating non-human models of immune diseases (ref. 4). Discovery of peptides driving the immune reactions causing human disease has been the obstacle to translating peptide-based therapeutic vaccines to clinical medicine.
Major international programmes are underway to discover and develop peptide-based therapeutic vaccines for multiple sclerosis, Type-1 diabetes, rheumatoid arthritis, and various allergic diseases including cat-sensitive asthma (ref. 4). Coeliac disease is uniquely suited for a peptide-based therapeutic vaccine because almost all patients possess either HLA DQ2 or DQ8, and patients with HLA DQ2 consistently recognise a defined set of gluten peptides following oral gluten challenge.