Authors
J Thompson1; J Derrick1; KJ Else1; 1 Lydia Becker Institute of Immunology & Inflammation, UK Discussion
Trichuriasis is a disease that affects ~465 million people worldwide resulting from infection by the intestinal dwelling parasitic nematode T. trichiura, colloquially known as the human whipworm. Whipworm infections can cause colitis, growth retardation, and Trichuris dysentery syndrome (TDS). The current treatment strategies for Trichuriasis and other soil transmitted helminths promoted by the World Health Organisation (WHO) involve mass drug administration (MDA) campaigns. However, the effectiveness of these MDA campaigns, particularly against T. trichiura, is poor. Low drug efficacy has fuelled the search for alternative treatments for Trichuriasis including the development of anti-T. trichiura vaccines which have the potential to provide long lasting immunity. However, these novel vaccines face many challenges in the field that must be addressed if they are to be considered as viable treatment options for Trichuriasis. Specifically, the infection status of the target population is a concern, with an emerging body of literature detailing the ability of some parasitic infections to dampen vaccine-mediated immune responses. Here we investigated the influence of pre-existing Trichuris infections on the effectiveness of vaccine-mediated immunity provided by anti-Trichuris vaccines via the Trichuris mouse model, T. muris. We employ a crude vaccine composed of excretory/secretory (E/S) products in alum. This vaccine is known to provide immunity to naïve C57BL/6 mice against subsequent T. muris infections. We demonstrate that a low dose infection of T. muris, administered to C57BL/6 mice prior to E/S vaccination, inhibits the protective immunity provided by E/S vaccination when delivered prior to a low dose infection. As the vast majority of individuals living in areas where T. trichiura is endemic harbour low-level chronic T. trichiura infections by a very early age, this research provides insight into some of the challenges that anti-T. trichiura vaccines will face in the field. 
