Vaccination With Trichuris muris Poly-Cysteine and Histidine-Tailed Protein p43 Protects Against Chronic Infection

Trichuris trichiura is one of the soil transmitted geohelminths which together currently affect approximately 25% of the global population resulting in considerable morbidity particularly in children and young adults. Recent estimates put infection by T. trichiura at approximately 513 million. De-worming programmes are often not completely effective against T. trichiura and fail to provide resistance to reinfection. Vaccination against these multicellular parasites has proved difficult as they have complex antigenic make-up and the potential to harness the host immune system to their own advantage. Previous vaccination experiments in mice using excretory secretory (ES) material have proved successful although the specific antigens responsible for protection have remained elusive. Here we show that vaccination of mice with native (n)p43, the dominant secreted protein from adult T. muris, formulated with Alum adjuvant can protect against chronic infection. The vaccine candidate generated a strong Type 2 response and host protection was dependent on signalling through IL-4 Rα. Vaccination with a recombinant (r)p43 formulated with alum resulted in stunted worms and reduced worm fecundity but no significant reduction in worm burden. Deglycosylation of np43 significantly abrogated protection against infection suggesting p43 glycans play a role in mediating the protective efficacy of np43. Vaccination using an adenoviral p43 construct generated a robust antibody response to np43 but no protection against challenge infection. Orthologues of p43 are present in other closely related nematodes including T. trichiura and T. suis which infects wild and domestic pigs, suggesting potential for similar vaccine development for both human and veterinary trichiuriasis.