Advances in vaccine development for human trichuriasis

Hayon, Jesica; Hotez, Peter J.; Bottazzi, María Elena; Zhan, Bin

doi:10.1017/s0031182021000500

Cited by 7 publications

(7 citation statements)

References 119 publications

(194 reference statements)

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“…Nevertheless, the need for a vaccine is clear, especially given the climate of emerging infectious diseases and the impact of STH infections on susceptibility to other pathogens and co-morbidities (Salgame et al ., 2013 ) (see also Hayes and Grencis, 2021 within this special issue). Vaccine development is discussed in detail by Hayon et al ( 2021 ) within this special issue.…”

Section: The Human Disease Trichuriasis As a Driver For T Muris Researchmentioning

confidence: 99%

Trichuris muris as a tool for holistic discovery research: from translational research to environmental bio-tagging

2021

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Section: The Human Disease Trichuriasis As a Driver For T Muris Researchmentioning

confidence: 99%

Trichuris muris as a tool for holistic discovery research: from translational research to environmental bio-tagging

2021

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“…Research advances in whipworm antigen discovery are reviewed in Hayon et al . (2021) which ends with a view of the global health policy needs if we are to develop and implement vaccine delivery in the field. Whilst a case can be made for anti-whipworm vaccine research based on the impact the parasite itself has on human health, whipworm infections also have substantial, widespread systemic effects despite being localized within the large intestine.…”

Section: Vaccine Developmentmentioning

confidence: 99%

“…Promising recombinant Ascaris antigens such as As14, As16 and As37(Tsuji et al, 2001;2002) have been identified and a recent study byde Castro et al (2021) outlines the use of a more intricate vaccine target, an adjuvanted chimeric protein derived from the three recombinants with an efficacy of 73.54% in BALB/c mice. Our continued paucity of knowledge of the totality of the Ascaris immune responses and the possibility that other undiscovered proteins may exist and act as better vaccine targets remain an ongoing challenge.Research advances in whipworm antigen discovery are reviewed inHayon et al (2021) which ends with a view of the global health policy needs if we are to develop and implement vaccine delivery in the field. Whilst a case can be made for anti-whipworm vaccine research based on the impact the parasite itself has on human health, whipworm infections also have substantial, widespread systemic effects despite being localised within the large intestine.Co-Morbidities, Immunomodulation and Co-Infectionhttps://www.cambridge.org/core/terms.…”

mentioning

confidence: 99%

Lessons from studying roundworm and whipworm in the mouse: common themes and unique features

Holland

Else

2021

Parasitology

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Ascaris lumbricoides, the roundworm, and Trichuris trichiura, the whipworm, are human intestinal nematode parasites; both are soil-transmitted helminths, are often placed together in an epidemiological context and both remain neglected despite high prevalence. Our understanding of parasitic disease continues to be enhanced through animal models. Despite the similarities between whipworm and roundworm, there are key differences between the two species and these have influenced the application of their respective animal models. In the case of T. trichiura, the fact that a murine equivalent, T. muris completes its life cycle in a mouse model has greatly enhanced our knowledge of whipworm biology, pathogenicity and immunology. In contrast, A. lumbricoides and its porcine equivalent, Ascaris suum, lack a rodent model in which the life cycle is completed. However, evidence continues to accumulate demonstrating that mice represent useful models of early Ascaris infection, a key stage of the life cycle. The use of mouse models for both Ascaris and Trichuris has a long history with early pioneers discovering fundamental aspects of each parasite's biology. Novel technologies and perspectives, as outlined in this special issue, demonstrate how through the prism of mouse models, we can continue to explore the similarities and differences between roundworms and whipworms.

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“…The infection causes malnutrition, diarrhea, anemia, and even rectal prolapse (4)(5)(6). The highest prevalence rates of infection occur in resource-poor regions of Southeast Asia, Sub-Saharan Africa, and the tropical regions of the Americas, where children carry the largest burden of T. trichiura infections (4,7,8). Most of these parasitized children are coinfected with other soiltransmitted helminths (STHs), further negatively impacting growth and cognitive development (9,10).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Advances in vaccine development for human trichuriasis

Abstract: Abstract

Cited by 7 publications

References 119 publications

Trichuris muris as a tool for holistic discovery research: from translational research to environmental bio-tagging

Trichuris muris as a tool for holistic discovery research: from translational research to environmental bio-tagging

Lessons from studying roundworm and whipworm in the mouse: common themes and unique features

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

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