{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T01:16:36Z","timestamp":1778980596498,"version":"3.51.4"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p><jats:italic>Trichuris trichiura<\/jats:italic> and <jats:italic>T<\/jats:italic>. <jats:italic>suis<\/jats:italic> are gastrointestinal dwelling roundworms that infect humans and pigs, respectively. Heavy infections cause gastrointestinal symptoms and impaired growth and development. Vaccination has the potential to reduce the disease burden of whipworm infection; however, there are currently no commercially available vaccines against these parasites and very few against other gastrointestinal-dwelling nematodes of medical and agricultural importance. The naturally occurring mouse whipworm, <jats:italic>T<\/jats:italic>. <jats:italic>muris<\/jats:italic>, has been used for decades to model human trichuriasis, and the immunogenic potential of the excretory\/secretory material (E\/S, which can be collected following ex vivo culture of worms) has been studied in the context of vaccine candidate identification. Despite this, researchers are yet to progress an effective vaccine candidate to clinical trials. The <jats:italic>T<\/jats:italic>. <jats:italic>muris<\/jats:italic>, <jats:italic>T<\/jats:italic>. <jats:italic>trichiura<\/jats:italic>, and <jats:italic>T<\/jats:italic>. <jats:italic>suis<\/jats:italic> genomes each encode between 10 and 27 whey acidic protein (WAP) domain-containing proteins and 15 to 34 cysteine-rich secretory protein\/antigen 5\/pathogenesis related-1 (CAP) family members. WAP and CAP proteins have been postulated to play key roles in host\u2013parasite interactions and may possess immunomodulatory functions. In addition, both protein families have been explored in the context of helminth vaccines. Here, we use phylogenetic and functional analysis to investigate the evolutionary relationship between WAP and CAP proteins encoded by <jats:italic>T<\/jats:italic>. <jats:italic>muris<\/jats:italic>, <jats:italic>T<\/jats:italic>. <jats:italic>trichiura<\/jats:italic>, and <jats:italic>T<\/jats:italic>. <jats:italic>suis<\/jats:italic>. We highlight several WAP and CAP proteins that warrant further study to understand their biological function and as possible vaccine candidates against <jats:italic>T<\/jats:italic>. <jats:italic>trichiura<\/jats:italic> and\/or <jats:italic>T<\/jats:italic>. <jats:italic>suis<\/jats:italic>, based on the close evolutionary relationship with WAP or CAP proteins identified within <jats:italic>T<\/jats:italic>. <jats:italic>muris<\/jats:italic> E\/S products.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010933","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T18:28:09Z","timestamp":1671733689000},"page":"e0010933","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Trichuris WAP and CAP proteins: Potential whipworm vaccine candidates?"],"prefix":"10.1371","volume":"16","author":[{"given":"Eleanor","family":"Wainwright","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0279-2801","authenticated-orcid":true,"given":"Rebecca K.","family":"Shears","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"issue":"1","key":"pntd.0010933.ref001","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41572-020-0171-3","article-title":"Whipworm and roundworm infections","volume":"6","author":"KJ Else","year":"2020","journal-title":"Nat Rev Dis Primers"},{"issue":"7","key":"pntd.0010933.ref002","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/ng.3010","article-title":"Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction","volume":"46","author":"BJ Foth","year":"2014","journal-title":"Nat Genet"},{"issue":"7","key":"pntd.0010933.ref003","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/ng.3012","article-title":"Genome and transcriptome of the porcine whipworm Trichuris suis","volume":"46","author":"AR Jex","year":"2014","journal-title":"Nat Genet"},{"issue":"9521","key":"pntd.0010933.ref004","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/S0140-6736(06)68653-4","article-title":"Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm","volume":"367","author":"J Bethony","year":"2006","journal-title":"Lancet"},{"issue":"3","key":"pntd.0010933.ref005","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1586\/14760584.2014.872035","article-title":"Advancing a multivalent \u2018Pan-anthelmintic\u2019 vaccine against soil-transmitted nematode infections","volume":"13","author":"B Zhan","year":"2014","journal-title":"Expert Rev Vaccines"},{"issue":"1","key":"pntd.0010933.ref006","first-page":"96","article-title":"Efficacy of Anthelminthic Drugs and Drug Combinations Against Soil-transmitted Helminths: A Systematic Review and Network Meta-analysis","volume":"68","author":"NE Clarke","year":"2019","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pntd.0010933.ref007","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ijpddr.2014.03.003","article-title":"Uptake of benzimidazoles by Trichuris suis in vivo in pigs","volume":"4","author":"TV Hansen","year":"2014","journal-title":"Int J Parasitol Drugs Drug Resist"},{"issue":"14","key":"pntd.0010933.ref008","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1017\/S0031182021000500","article-title":"Advances in vaccine development for human trichuriasis","volume":"148","author":"J Hayon","year":"2021","journal-title":"Parasitology"},{"issue":"1","key":"pntd.0010933.ref009","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1186\/s13071-022-05483-5","article-title":"Whipworm secretions and their roles in host-parasite interactions","volume":"15","author":"RK Shears","year":"2022","journal-title":"Parasit Vectors"},{"key":"pntd.0010933.ref010","doi-asserted-by":"crossref","first-page":"576748","DOI":"10.3389\/fimmu.2020.576748","article-title":"Soil-Transmitted Helminth Vaccines: Are We Getting Closer?","volume":"11","author":"A Zawawi","year":"2020","journal-title":"Front Immunol"},{"issue":"14","key":"pntd.0010933.ref011","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0020-7519(01)00281-8","article-title":"The effect of challenge and trickle Trichuris muris infections on the polarisation of the immune response","volume":"31","author":"AJ Bancroft","year":"2001","journal-title":"Int J Parasitol"},{"issue":"Pt 1","key":"pntd.0010933.ref012","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1017\/S0031182000057188","article-title":"Functional antigens of Trichuris muris released during in vitro maintenance: their immunogenicity and partial purification","volume":"86","author":"SN Jenkins","year":"1983","journal-title":"Parasitology"},{"issue":"1","key":"pntd.0010933.ref013","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1038\/s41598-018-22783-y","article-title":"Vaccination Against Whipworm: Identification of Potential Immunogenic Proteins in Trichuris muris Excretory\/Secretory Material","volume":"8","author":"RK Shears","year":"2018","journal-title":"Sci Rep"},{"issue":"8","key":"pntd.0010933.ref014","doi-asserted-by":"crossref","first-page":"e1007273","DOI":"10.1371\/journal.ppat.1007273","article-title":"Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm","volume":"14","author":"N Briggs","year":"2018","journal-title":"PLoS Pathog"},{"key":"pntd.0010933.ref015","doi-asserted-by":"crossref","first-page":"800295","DOI":"10.3389\/fimmu.2022.800295","article-title":"Mucosal Vaccination With Recombinant Tm-WAP49 Protein Induces Protective Humoral and Cellular Immunity Against Experimental Trichuriasis in AKR Mice","volume":"13","author":"J Wei","year":"2022","journal-title":"Front Immunol"},{"issue":"3","key":"pntd.0010933.ref016","doi-asserted-by":"crossref","first-page":"e1008243","DOI":"10.1371\/journal.ppat.1008243","article-title":"In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection","volume":"16","author":"A Zawawi","year":"2020","journal-title":"PLoS Pathog"},{"issue":"1","key":"pntd.0010933.ref017","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1038\/s41467-019-09996-z","article-title":"The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function","volume":"10","author":"AJ Bancroft","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"pntd.0010933.ref018","doi-asserted-by":"crossref","first-page":"1428004","DOI":"10.1080\/20013078.2018.1428004","article-title":"Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication","volume":"7","author":"RM Eichenberger","year":"2018","journal-title":"J Extracell Vesicles"},{"key":"pntd.0010933.ref019","unstructured":"WormBase ParaSite Version: WBPS16 (WS279). Release 16\u2014September 2021 [cited 2022 Jun 21]. https:\/\/parasite.wormbase.org\/index.html."},{"issue":"5","key":"pntd.0010933.ref020","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1042\/BST0391409","article-title":"WAP domain proteins as modulators of mucosal immunity","volume":"39","author":"TS Wilkinson","year":"2011","journal-title":"Biochem Soc Trans"},{"issue":"9","key":"pntd.0010933.ref021","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.jprot.2011.06.002","article-title":"Proteomic analysis of secretory products from the model gastrointestinal nematode Heligmosomoides polygyrus reveals dominance of venom allergen-like (VAL) proteins","volume":"74","author":"JP Hewitson","year":"2011","journal-title":"J Proteomics"},{"issue":"10","key":"pntd.0010933.ref022","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1074\/mcp.M114.038950","article-title":"Secreted proteomes of different developmental stages of the gastrointestinal nematode Nippostrongylus brasiliensis","volume":"13","author":"J Sotillo","year":"2014","journal-title":"Mol Cell Proteomics"},{"issue":"12","key":"pntd.0010933.ref023","first-page":"6672","article-title":"Cloning and characterization of Ancylostoma-secreted protein. A novel protein associated with the transition to parasitism by infective hookworm larvae","volume":"271","author":"JM Hawdon","year":"1996","journal-title":"J Biol Chem"},{"issue":"Pt 4","key":"pntd.0010933.ref024","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1107\/S1744309105007748","article-title":"Crystallization and preliminary X-ray analysis of Na-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite Necator americanus","volume":"61","author":"OA Asojo","year":"2005","journal-title":"Acta Crystallogr Sect F Struct Biol Cryst Commun"},{"issue":"3","key":"pntd.0010933.ref025","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.jmb.2004.12.023","article-title":"X-ray structure of Na-ASP-2, a pathogenesis-related-1 protein from the nematode parasite, Necator americanus, and a vaccine antigen for human hookworm infection","volume":"346","author":"OA Asojo","year":"2005","journal-title":"J Mol Biol"},{"issue":"1","key":"pntd.0010933.ref026","doi-asserted-by":"crossref","first-page":"15921","DOI":"10.1038\/s41598-018-34174-4","article-title":"Analysis of the Trichuris suis excretory\/secretory proteins as a function of life cycle stage and their immunomodulatory properties","volume":"8","author":"LP Leroux","year":"2018","journal-title":"Sci Rep"},{"key":"pntd.0010933.ref027","first-page":"4342789","article-title":"Identification, Characterization, and Structure of Tm16 from Trichuris muris","volume":"2017","author":"Z Liu","year":"2017","journal-title":"J Parasitol Res"},{"issue":"8","key":"pntd.0010933.ref028","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1093\/nar\/10.8.2677","article-title":"Mouse whey acidic protein is a novel member of the family of \u2018four-disulfide core\u2019 proteins","volume":"10","author":"LG Hennighausen","year":"1982","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pntd.0010933.ref029","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jaci.2012.04.027","article-title":"Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths","volume":"130","author":"DJ Diemert","year":"2012","journal-title":"J Allergy Clin Immunol"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010933","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T18:28:27Z","timestamp":1671733707000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010933"}},"subtitle":[],"editor":[{"given":"Bruce A.","family":"Rosa","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,22]]},"references-count":29,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0010933","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,22]]}}}