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Advancing a multivalent 'Pan-anthelmintic' vaccine against soil-transmitted nematode infections.

Zhan B, Beaumier CM, Briggs N, Jones KM, Keegan BP, Bottazzi ME, Hotez PJ - Expert Rev Vaccines (2014)

Bottom Line: Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively.Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions.Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.

View Article: PubMed Central - PubMed

Affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine , Houston, TX , USA.

ABSTRACT
The Sabin Vaccine Institute Product Development Partnership is developing a Pan-anthelmintic vaccine that simultaneously targets the major soil-transmitted nematode infections, in other words, ascariasis, trichuriasis and hookworm infection. The approach builds off the current bivalent Human Hookworm Vaccine now in clinical development and would ultimately add both a larval Ascaris lumbricoides antigen and an adult-stage Trichuris trichiura antigen from the parasite stichosome. Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively. Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions. Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.

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Related in: MedlinePlus

The stichosome of Trichuris spp. Single row of gland cells (stichocytes) in the esophagus of Trichuris suis; this characteristic structure of the esophagus is unique to enoplid nematodes.
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Figure 1: The stichosome of Trichuris spp. Single row of gland cells (stichocytes) in the esophagus of Trichuris suis; this characteristic structure of the esophagus is unique to enoplid nematodes.

Mentions: Trichuris trichiura is a parasite of the superfamily Trichinelloidea, known as the common whipworm of humans and nonhuman primates. Due to its host specificity, there is no established laboratory animal model for this pathogen. Fortunately, the closely related Trichuris muris parasite, specific for rats and mice, has emerged as a useful surrogate for immunogenicity and efficacy models. Additionally, animal models for Trichinella spiralis (a cause of trichinellosis), also a member of the Trichinelloidea superfamily, exhibit some immunological similarities for Trichuris sp. Both Trichuris sp. and Trichinella sp. possess a unique stichosome – a modified esophagus and esophageal gland that contains longitudinally arranged cells known as stichocytes – which is a rich source of ES antigens (Figure 1). Such ES antigens are produced in the stichosome and released through the anterior ends of adult whipworms embedded in the colonic mucosa. The stichosome and its stichocytes are being explored through proteomics approaches.


Advancing a multivalent 'Pan-anthelmintic' vaccine against soil-transmitted nematode infections.

Zhan B, Beaumier CM, Briggs N, Jones KM, Keegan BP, Bottazzi ME, Hotez PJ - Expert Rev Vaccines (2014)

The stichosome of Trichuris spp. Single row of gland cells (stichocytes) in the esophagus of Trichuris suis; this characteristic structure of the esophagus is unique to enoplid nematodes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3934375&req=5

Figure 1: The stichosome of Trichuris spp. Single row of gland cells (stichocytes) in the esophagus of Trichuris suis; this characteristic structure of the esophagus is unique to enoplid nematodes.
Mentions: Trichuris trichiura is a parasite of the superfamily Trichinelloidea, known as the common whipworm of humans and nonhuman primates. Due to its host specificity, there is no established laboratory animal model for this pathogen. Fortunately, the closely related Trichuris muris parasite, specific for rats and mice, has emerged as a useful surrogate for immunogenicity and efficacy models. Additionally, animal models for Trichinella spiralis (a cause of trichinellosis), also a member of the Trichinelloidea superfamily, exhibit some immunological similarities for Trichuris sp. Both Trichuris sp. and Trichinella sp. possess a unique stichosome – a modified esophagus and esophageal gland that contains longitudinally arranged cells known as stichocytes – which is a rich source of ES antigens (Figure 1). Such ES antigens are produced in the stichosome and released through the anterior ends of adult whipworms embedded in the colonic mucosa. The stichosome and its stichocytes are being explored through proteomics approaches.

Bottom Line: Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively.Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions.Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.

View Article: PubMed Central - PubMed

Affiliation: Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, National School of Tropical Medicine, Baylor College of Medicine , Houston, TX , USA.

ABSTRACT
The Sabin Vaccine Institute Product Development Partnership is developing a Pan-anthelmintic vaccine that simultaneously targets the major soil-transmitted nematode infections, in other words, ascariasis, trichuriasis and hookworm infection. The approach builds off the current bivalent Human Hookworm Vaccine now in clinical development and would ultimately add both a larval Ascaris lumbricoides antigen and an adult-stage Trichuris trichiura antigen from the parasite stichosome. Each selected antigen would partially reproduce the protective immunity afforded by UV-attenuated Ascaris eggs and Trichuris stichosome extracts, respectively. Final antigen selection will apply a ranking system that includes the evaluation of expression yields and solubility, feasibility of process development and the absence of circulating antigen-specific IgE among populations living in helminth-endemic regions. Here we describe a five year roadmap for the antigen discovery, feasibility and antigen selection, which will ultimately lead to the scale-up expression, process development, manufacture, good laboratory practices toxicology and preclinical evaluation, ultimately leading to Phase 1 clinical testing.

Show MeSH
Related in: MedlinePlus