Genetic Mapping Identifies Novel Highly Protective Antigens for an Apicomplexan Parasite

PLoS Pathogens

Michael A. Quail¹  Richard D. Oakes¹  Damer P. Blake¹  Susan L. Copestake¹  Martin W. Shirley²  Karen J. Billington³  Adrian L. Smith⁴  Kiew-Lian Wan⁵ 

[1] Institute for Animal Health, Compton, Berkshire, United Kingdom;Malaysia Genome Institute, UKM-MTDC Technology Centre, Selangor, Malaysia;Pathology and Infectious Diseases, Royal Veterinary College, University of London, North Mymms, United Kingdom;School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia;Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom

关键词: Eimeria;    Polymerase chain reaction;    Immunity;    Oocysts;    Genetic loci;    Bird genomics;    Chickens;    Parasitic diseases;   

DOI  :  10.1371/journal.ppat.1001279

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Apicomplexan parasites are responsible for a myriad of diseases in humans and livestock; yet despite intensive effort, development of effective sub-unit vaccines remains a long-term goal. Antigenic complexity and our inability to identify protective antigens from the pool that induce response are serious challenges in the development of new vaccines. Using a combination of parasite genetics and selective barriers with population-based genetic fingerprinting, we have identified that immunity against the most important apicomplexan parasite of livestock (Eimeria spp.) was targeted against a few discrete regions of the genome. Herein we report the identification of six genomic regions and, within two of those loci, the identification of true protective antigens that confer immunity as sub-unit vaccines. The first of these is an Eimeria maxima homologue of apical membrane antigen-1 (AMA-1) and the second is a previously uncharacterised gene that we have termed ‘immune mapped protein-1’ (IMP-1). Significantly, homologues of the AMA-1 antigen are protective with a range of apicomplexan parasites including Plasmodium spp., which suggest that there may be some characteristic(s) of protective antigens shared across this diverse group of parasites. Interestingly, homologues of the IMP-1 antigen, which is protective against E. maxima infection, can be identified in Toxoplasma gondii and Neospora caninum. Overall, this study documents the discovery of novel protective antigens using a population-based genetic mapping approach allied with a protection-based screen of candidate genes. The identification of AMA-1 and IMP-1 represents a substantial step towards development of an effective anti-eimerian sub-unit vaccine and raises the possibility of identification of novel antigens for other apicomplexan parasites. Moreover, validation of the parasite genetics approach to identify effective antigens supports its adoption in other parasite systems where legitimate protective antigen identification is difficult.

【 授权许可】

CC BY