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

Front Immunol. 2022 Feb 7:13:800295. doi: 10.3389/fimmu.2022.800295. eCollection 2022.


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.

Keywords: Tm-WAP49; Trichuriasis; adjuvants; intranasal immunization; mucosal immunity; vaccine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred BALB C
  • Mucous Membrane / immunology
  • Th1 Cells / immunology
  • Trichuriasis / immunology*
  • Trichuris / immunology
  • Vaccination / methods
  • Vaccines, Synthetic


  • Adjuvants, Immunologic
  • Immunoglobulin A
  • Immunoglobulin G
  • Vaccines, Synthetic