Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome of Giardia lamblia
| Autor: | Kurt Hanevik, Marcela Ferella, Matej Radunovic, Ching M. Liu, Nina Langeland, Elaine M. Hanson, Staffan G. Svärd, Marvin Fischer, Majid Ghassemian, Jonathan Ang, Lars Eckmann, Christine Le, Barbara J. Davids, Yukiko Miyamoto |
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| Přispěvatelé: | Herbert, De'Broski R |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Giardiasis Male Protozoan Vaccines and promotion of well-being Proteome Protozoan Proteins Antibodies Protozoan medicine.disease_cause Proteomics Inbred C57BL Medical and Health Sciences Mass Spectrometry law.invention Mice 0302 clinical medicine law Peptide sequence Effector vaccines Biological Sciences Middle Aged Foodborne Illness Infectious Diseases 3.4 Vaccines Protozoan Microbial Immunity and Vaccines Recombinant DNA Zero Hunger Female Infection Biotechnology Adult 030231 tropical medicine Immunology Antigens Protozoan Biology Cross Reactions immunization Microbiology Antibodies Vaccine Related 03 medical and health sciences Young Adult Antigen Biodefense medicine Giardia lamblia Animals Humans Antigens Agricultural and Veterinary Sciences Prevention Prevention of disease and conditions Virology surface antigens Mice Inbred C57BL 030104 developmental biology Emerging Infectious Diseases Immunization Parasitology Digestive Diseases |
| Zdroj: | Infection and immunity, vol 87, iss 6 |
| ISSN: | 1098-5522 |
| Popis: | 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), α1-giardin, and α11-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. |
| Databáze: | OpenAIRE |
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