Mucosal Vaccination With Recombinant Tm- WAP49 Protein Induces Protective Humoral and Cellular Immunity Against Experimental Trichuriasis in AKR Mice

• Published in: Frontiers in immunology 2022-02, Vol.13, p.800295-800295
• Main Authors: Wei, Junfei, Hegde, Venkatesh L, Yanamandra, Ananta V, O'Hara, Madison P, Keegan, Brian, Jones, Kathryn M, Strych, Ulrich, Bottazzi, Maria Elena, Zhan, Bin, Sastry, K Jagannadha, Hotez, Peter J
• Format: Article
• Language: English
• Subjects: adjuvants; Adjuvants, Immunologic - pharmacology; Administration, Intranasal; Animals; Antibody Formation - drug effects; CD8-Positive T-Lymphocytes - immunology; Female; Immunity, Cellular - drug effects; Immunity, Mucosal - immunology; Immunization; Immunoglobulin A - immunology; Immunoglobulin G - immunology; Immunology; intranasal immunization; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; mucosal immunity; Mucous Membrane - immunology; Th1 Cells - immunology; Tm-WAP49; Trichuriasis; Trichuriasis - immunology; Trichuris - immunology; Vaccination - methods; vaccine; Vaccines, Synthetic
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.800295

Trichuriasis is one of the most common neglected tropical diseases of the world's poorest people. A recombinant vaccine composed of WAP49, an immunodominant antigen secreted by adult 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 infection, with the ultimate goal of producing a mucosal vaccine through intranasal delivery. Intranasal immunization of mice with 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 -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 WAP49 protein induced strong protection versus murine trichuriasis. It represents a promising vaccination approach against intestinal nematodes.