Advancing a multivalent ‘Pan-anthelmintic’ vaccine against soil-transmitted nematode infections

Zhan, Bin; Beaumier, Coreen M; Briggs, Neima; Jones, Kathryn M; Keegan, Brian P; Bottazzi, Maria Elena; Hotez, Peter J

antigens (FIGURE 1). Such ES antigens are produced in the stichosome and released through the anterior ends of adult whipworms embedded in the colonic mucosa. The stichosome and its stichocytes are being explored through proteomics approaches. Both T. trichiura and T. muris follow a similar oral-fecal life cycle. Once embryonated eggs are ingested, they hatch in the small intestine. The larvae then mature and develop to adult worms in the cecum and ascending colon [49] . Different mouse strains vary in their degree of resistance or susceptibility to T. muris. The most notable strains are BALB/c (resistant) and AKR (susceptible) mice. BALB/c mice exhibit a T H 2-skewed immune protective response against T. muris, associated with elevations in host IL-4 and IgG1 [49, [51] [52] [53] . In addition to the T. muris-specific adaptive immune response, innate responses have also been identified including a multipotent progenitor type 2 cell population in the gut-associated lymphoid tissue that is induced by IL-25 and can differentiate into innate immune cells such as monocytes, macrophages, mast cells and basophils [54] . Furthermore, an interesting mechanism of parasite expulsion has been linked to the aforementioned cytokine profiles. This mechanism is known as the 'epithelial escalator' in which the epithelial cells migrate from the crypt area to the top of the epithelium while bringing the parasite along with it and ultimately shedding the parasite [55] . This phenomenon appeared to be more efficient in the resistant BALB/c model compared with the susceptible AKR model [55] . Additionally, this turnover was linked to the cytokine profiles where T H 2 responses were linked to the upregulation of turnover, and T H 1 responses were correlated with downregulation of turnover [55] .