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Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia
Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
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2019 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 87, no 6, article id e00219-19Article in journal (Refereed) Published
Abstract [en]

Giardia lamblia, one of the most common protozoal infections of the human intestine, is an important worldwide cause of diarrheal disease, malabsorption, malnutrition, delayed cognitive development in children, and protracted postinfectious syndromes. Despite its medical importance, no human vaccine is available against giardiasis. A crude veterinary vaccine has been developed, and experimental vaccines based on expression of multiple variant-specific surface proteins have been reported, but poorly defined vaccine components and excessive antigen variability are problematic for pharmaceutical vaccine production. To expand the repertoire of antigen candidates for vaccines, we reasoned that surface proteins may provide an enriched source of such antigens since key host effectors, such as secretory IgA, can directly bind to such antigens in the intestinal lumen and interfere with epithelial attachment. Here, we have applied a proteomics approach to identify 23 novel surface antigens of G. lamblia that show >90% amino acid sequence identity between the two human-pathogenic genetic assemblages (A and B) of the parasite. Surface localization of a representative subset of these proteins was confirmed by immunostaining. Four selected proteins, uridine phosphorylase-like protein-1, protein 21.1 (GL50803_ 27925), alpha 1-giardin, and alpha 11-giardin, were subsequently produced in recombinant form and shown to be immunogenic in mice and G. lamblia-infected humans and confer protection against G. lamblia infection upon intranasal immunization in rodent models of giardiasis. These results demonstrate that identification of conserved surface antigens provides a powerful approach for overcoming a key rate-limiting step in the design and construction of an effective vaccine against giardiasis.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY , 2019. Vol. 87, no 6, article id e00219-19
Keywords [en]
giardiasis, immunization, surface antigens, vaccines
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:uu:diva-385959DOI: 10.1128/IAI.00219-19ISI: 000468521100017PubMedID: 30962402OAI: oai:DiVA.org:uu-385959DiVA, id: diva2:1327467
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NIH (National Institute of Health), AI112594Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-06-19Bibliographically approved

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Ferella, MarcelaSvärd, Staffan

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