{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:58:27Z","timestamp":1753891107465,"version":"3.41.2"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Trichuriasis is one of the most common neglected tropical diseases of the world\u2019s poorest people. A recombinant vaccine composed of<jats:italic>Tm-<\/jats:italic>WAP49, an immunodominant antigen secreted by adult<jats:italic>Trichuris<\/jats:italic>stichocytes into the mucosa of the cecum to which the parasite attaches, is under development. The prototype is being evaluated in a mouse model of<jats:italic>Trichuris muris<\/jats:italic>infection, with the ultimate goal of producing a mucosal vaccine through intranasal delivery. Intranasal immunization of mice with<jats:italic>Tm-<\/jats:italic>WAP49 formulated with the adjuvant OCH, a truncated analog of alpha-GalCer with adjuvanticity to stimulate natural killer T cells (NKT) and mucosal immunity, induced significantly high levels of IgG and its subclasses (IgG1 and IgG2a) in immunized mice. This also resulted in a significant reduction of worm burden after challenge with<jats:italic>T. muris<\/jats:italic>-infective eggs. The addition of QS-21 adjuvant to this vaccine formulation further reduced worm counts. The improved protection from the dual-adjuvanted vaccine correlated with higher serum antibody responses (IgG, IgG1, IgG2a, IgA) as well as with the induction of antigen-specific IgA in the nasal mucosa. It was also associated with the robust cellular responses including functional subsets of CD4 T cells producing IL-4, and cytotoxic CD8 T cells expressing granzyme B. The worm reduction achieved by mucosal immunization was higher than that induced by subcutaneous immunization. Intranasal immunization also induced a significantly higher nasal mucosa-secreted antigen-specific IgA response, as well as higher functional cellular responses including CD4<jats:sup>+<\/jats:sup>IL4<jats:sup>+<\/jats:sup>(Th1) and CD8<jats:sup>+<\/jats:sup>GnzB<jats:sup>+<\/jats:sup>(Th2) T cells, and antigen-specific INF\u03b3-producing T cells in both spleen and MLNs and antibody-producing B cells (CD19<jats:sup>+<\/jats:sup>B220<jats:sup>+<\/jats:sup>\/B220<jats:sup>+<\/jats:sup>GL7<jats:sup>+<\/jats:sup>). Mucosal immunization further induced long-term T lymphocyte memory with increased central (CD62L<jats:sup>+<\/jats:sup>CD44<jats:sup>+<\/jats:sup>) and effector (CD62L<jats:sup>-<\/jats:sup>CD44<jats:sup>+<\/jats:sup>) memory subsets of both CD4 and CD8 T cells at 60 days after the last immunization. In summary, intranasal immunization with recombinant<jats:italic>Tm-<\/jats:italic>WAP49 protein induced strong protection versus murine trichuriasis. It represents a promising vaccination approach against intestinal nematodes.<\/jats:p>","DOI":"10.3389\/fimmu.2022.800295","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T06:57:41Z","timestamp":1644217061000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Mucosal Vaccination With Recombinant Tm-WAP49 Protein Induces Protective Humoral and Cellular Immunity Against Experimental Trichuriasis in AKR Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Junfei","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venkatesh L.","family":"Hegde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananta V.","family":"Yanamandra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison P.","family":"O\u2019Hara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Keegan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn M.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Strych","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Elena","family":"Bottazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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