Extracellular vesicles induce protective immunity against Trichuris muris

Abstract

Gastrointestinal nematodes, such as Trichuris trichiura (human whipworm), are a major source of morbidity in humans and their livestock. There is a paucity of commercially available vaccines against these parasites, and vaccine development for T. trichiura has been impeded by a lack of known host protective antigens. Experimental vaccinations with T. muris (murine whipworm) soluble Excretory/Secretory (ES) material have demonstrated that it is possible to induce protective immunity in mice; however, the potential for extracellular vesicles (EVs) as a source of antigenic material has remained relatively unexplored. Here, we demonstrate that EVs isolated from T. muris ES can induce protective immunity in mice when administered as a vaccine without adjuvant and show that the protective properties of these EVs are dependent on intact vesicles. We also identified several proteins within EV preparations that are targeted by the host antibodies following vaccination and subsequent infection with T. muris. Many of these proteins, including VWD and vitellogenin N and DUF1943‐domain‐containing protein, vacuolar protein sorting‐associated protein 52 and TSP‐1 domain‐containing protein, were detected in both soluble ES and EV samples and have homologues in other parasites of medical and veterinary importance, and as such are possible protective antigens.

Proteomic Analysis Of Trichuris Trichiura Egg Extract Reveals Potential Immunomodulators And Diagnostic Targets

“…They are produced by extraovarian tissues, secreted into the circulatory system and then taken up by the developing oocytes through receptor mediated endocytosis to provide the growing embryo with amino acids [36]. On the other hand, the detection of PCHTP-2 as the second most frequently detected protein is in accordance to Shears and collaborators [37] who found it to be the most abundant protein in the T. muris adult secretome; even though a speci c function has not been assigned yet. Likewise, Bancroft and collaborators [38] identi ed PCHTP-2 as the most abundant protein in cecal mucus from chronically infected mice with T. muris and con rmed its expression in all developmental stages.…”

“…Shears and collaborators [37] identi ed VgNVD in extracellular vesicles (EVs) of T. muris as a potential immunogenic candidate. Antigenic homologs have been identi ed in both free-living nematodes such as C. elegans, and adult parasites secretomes of Ascaris suum, Nippostrongylus brasiliensis, Heligmosomoides polygyrus and Litomosoides sigmodontis [56][57][58][59] and also in H. polygyrus eggs [60].…”

Trichinella spiralis muscle larvae release extracellular vesicles with immunomodulatory properties

“…Helminths produce EVs which are involved in parasite‐parasite and in parasite‐host communication . They can be released by the tegument and are found in ES products .…”

“…5 Helminths produce EVs which are involved in parasite-parasite and in parasite-host communication. [6][7][8][9][10] They can be released by the tegument and are found in ES products. 7 Although not associated with the term EVs at the time, vesicles were first detected on the tegument surfaces of Fasciola hepatica and Echinostoma caproni.…”

Schistosoma haematobiumextracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

“…EVs from helminths also contain vaccine candidate antigens. For example, EVs from S. mansoni contain molecules that have known vaccine efficacy in animal models of schistosomiasis [27], and vaccination of mice with helminth EVs stimulates the production of protective immune responses that significantly reduce faecal egg counts, worm burdens and symptom severity and mortality induced by infection after parasite challenge [25,41-44]. Moreover, antibodies produced against recombinant forms of Opisthorchis viverrini EV surface proteins hinders the uptake of EVs by cholangiocytes and suppresses the immune response that fuels pathogenesis [29,42].…”