{"doi":"10.3389/fimmu.2022.800295","title":"Mucosal Vaccination With Recombinant Tm-WAP49 Protein Induces Protective Humoral and Cellular Immunity Against Experimental Trichuriasis in AKR Mice","abstract":"Trichuriasis is one of the most common neglected tropical diseases of the world’s poorest people. A recombinant vaccine composed of Tm- WAP49, an immunodominant antigen secreted by adult Trichuris 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 Trichuris muris infection, with the ultimate goal of producing a mucosal vaccine through intranasal delivery. Intranasal immunization of mice with Tm- 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 T. muris -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 + IL4 + (Th1) and CD8 + GnzB + (Th2) T cells, and antigen-specific INFγ-producing T cells in both spleen and MLNs and antibody-producing B cells (CD19 + B220 + /B220 + GL7 + ). Mucosal immunization further induced long-term T lymphocyte memory with increased central (CD62L + CD44 + ) and effector (CD62L - CD44 + ) memory subsets of both CD4 and CD8 T cells at 60 days after the last immunization. In summary, intranasal immunization with recombinant Tm- WAP49 protein induced strong protection versus murine trichuriasis. It represents a promising vaccination approach against intestinal nematodes.","journal":"Frontiers in Immunology","year":2022,"id":281996,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":557406,"name":"Venkatesh L. Hegde","orcid":"0000-0002-0949-919X","position":1,"is_corresponding":false},{"id":826783,"name":"Ananta V. Yanamandra","orcid":null,"position":2,"is_corresponding":false},{"id":957642,"name":"Madison P. O’Hara","orcid":"0009-0009-2435-3410","position":3,"is_corresponding":false},{"id":378361,"name":"Brian Keegan","orcid":"0000-0001-9140-8690","position":4,"is_corresponding":false},{"id":378362,"name":"Kathryn M. Jones","orcid":"0000-0001-8745-1987","position":5,"is_corresponding":false},{"id":231474,"name":"Ulrich Strych","orcid":"0000-0001-9455-7683","position":6,"is_corresponding":false},{"id":231472,"name":"María Elena Bottazzi","orcid":"0000-0002-8429-0476","position":7,"is_corresponding":false},{"id":342530,"name":"Bin Zhan","orcid":"0000-0002-6884-9452","position":8,"is_corresponding":false},{"id":279025,"name":"K. Jagannadha Sastry","orcid":"0000-0002-6987-4422","position":9,"is_corresponding":false},{"id":42798,"name":"Peter J. Hotez","orcid":"0000-0001-8770-1042","position":10,"is_corresponding":false},{"id":553628,"name":"Junfei Wei","orcid":"0000-0002-0041-5535","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T00:29:15.734856Z","pmid":"35197976","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}