Identification and characterization of a new 34 kDa MORN motif-containing sporozoite surface-exposed protein,Cp-P34, unique to Cryptosporidium |
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| Institution: | 1. Center for Global Health and Diseases, Case Western Reserve University, Biomedical Research Building, 2109 Adelbert Rd., Cleveland, OH 44106, USA;2. University of New Mexico, Department of Anthropology, Albuquerque, 1 University of New Mexico, NM 87131, USA;3. Bahiana School of Medicine and Public Health, Av. Silveira Martins, n° 3386, Salvador, Bahia 41150-100, Brazil;4. Gonçalo Moniz Research Centre, Oswaldo Cruz Foundation, Rua Waldemar Falcão, 121 Brotas, Salvador, Bahia 40296-710, Brazil;5. School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil;6. Yale School of Public Health, Yale University, New Haven, CT, USA;7. Department of Tropical Medicine, Tulane School of Public Health and Tropical Medicine, Tidewater Building, 1440 Canal Street, New Orleans, LA 70112, USA;1. Instituto de Patobiología Veterinaria (INTA-CONICET), CICVyA, INTA-Castelar, 1686 Hurlingham, Argentina;2. CONICET, Ciudad de Buenos Aires, Argentina;1. Biology Department, Mills College, 5000 MacArthur Blvd., Oakland, CA 94631, USA;2. Odum School of Ecology, University of Georgia, 140 E Green St, Athens, GA 30602, USA;3. Department of Environmental Science and Policy, University of California Davis, One Shields Avenue, Davis, CA 95616, USA;1. Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo, Brazil;2. Nucleo de Microscopia Eletrônica, Instituto Adolfo Lutz, Sao Paulo, Brazil;3. Laboratório Regional de Sorocaba, Instituto Adolfo Lutz, Sao Paulo, Brazil;4. Centro de Patologia, Instituto Adolfo Lutz, Sao Paulo, Brazil;5. Departamento de Morfologia e Patologia, Faculdade de Ciências Médicas e Saúde, Pontifícia Universidade Católica, São Paulo, Brazil;1. School of Biological Sciences, Queen’s University Belfast, Belfast, UK;2. Agri-Food and Biosciences Institute (AFBI), Belfast, UK;1. School of Veterinary Medicine & Science, University of Nottingham, Sutton Boningto, LE12 5RD, UK;2. Department of Infection Biology, Institute of Infection & Global Health, University of Liverpool, L3 5RF, UK;3. Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Thailand |
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| Abstract: | Despite the public health impact of childhood diarrhea caused by Cryptosporidium, effective drugs and vaccines against this parasite are unavailable. Efforts to identify vaccine targets have focused on critical externally exposed virulence factors expressed in the parasite s invasive stages. However, no single surface antigen has yet been found that can elicit a significant protective immune response and it is likely that pooling multiple immune targets will be necessary. Discovery of surface proteins on Cryptosporidium sporozoites is therefore vital to this effort to develop a multi-antigenic vaccine. In this study we applied a novel single-domain camelid antibody (VHH) selection method to identify immunogenic proteins expressed on the surface of Cryptosporidium parvum sporozoites. By this approach, VHHs were identified that recognize two sporozoite surface-exposed antigens, the previously identified gp900 and an unrecognized immunogenic protein, Cp-P34. This Cp-P34 antigen, which contains multiple Membrane Occupation and Recognition Nexus (MORN) repeats, is found in excysted sporozoites as well as in the parasite s intracellular stages. Cp-P34 appears to accumulate inside the parasite and transiently appears on the surface of sporozoites to be shed in trails. Identical or nearly identical orthologs of Cp-P34 are found in the Cryptosporidium hominis and Cryptosporidium tyzzeri genomes. Except for the conserved MORN motifs, the Cp-P34 gene shares no significant homology with genes of other protozoans and thus appears to be unique to Cryptosporidium spp. Cp-P34 elicits immune responses in naturally exposed alpacas and warrants further investigation as a potential vaccine candidate. |
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| Keywords: | Sporozoite Surface antigen MORN VHH P34 gp900 |
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