Journal Article

Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development

Abdalgader Moftah, Venkatachalam Thenmozhi, Kumarasamy Thangaraj, Rajat Garg, Emily L. Clark, Adam James Reid, Fiona M. Tomley, Damer P. Blake, M. Raman, Sarah E. Macdonald, Arni S. R. Srinivasa Rao, Partha S. Banerjee, G. Dhinakar-Raj, Simeon Ayoade, Ramón Álvarez Zapata, Krishnendu Kundu, Isa D. Jatau, Fumiya Kawahara, Ayotunde O. Adebambo

2015

Overview

Sixty billion chickens are produced worldwide each year, and all are at risk from Eimeria , parasites that cause coccidiosis. Control relies widely on chemoprophylaxis, but pressure to reduce drug use in farming urges development of cost-effective vaccines. Antigens such as apical membrane antigen 1 (AMA1) offer promise as anticoccidial vaccine candidates, but experience with related apicomplexans such as Plasmodium , in which pre-existing antigenic diversity and incompatible population structure have undermined vaccine development, tempers confidence. Parasite genotyping identified enormous region-specific variation in haplotype diversity for Eimeria tenella but a contrastingly low level of polymorphism for Et AMA1. Although high levels of polyclonal Eimeria infection and hybridization indicate an ability to disseminate vaccine resistance rapidly, the low level of Et AMA1 diversity promotes vaccine development. The phylum Apicomplexa includes serious pathogens of humans and animals. Understanding the distribution and population structure of these protozoan parasites is of fundamental importance to explain disease epidemiology and develop sustainable controls. Predicting the likely efficacy and longevity of subunit vaccines in field populations relies on knowledge of relevant preexisting antigenic diversity, population structure, the likelihood of coinfection by genetically distinct strains, and the efficiency of cross-fertilization. All four of these factors have been investigated for Plasmodium species parasites, revealing both clonal and panmictic population structures with exceptional polymorphism associated with immunoprotective antigens such as apical membrane antigen 1 (AMA1). For the coccidian Toxoplasma gondii only genomic diversity and population structure have been defined in depth so far; for the closely related Eimeria species, all four variables are currently unknown. Using Eimeria tenella , a major cause of the enteric disease coccidiosis, which exerts a profound effect on chicken productivity and welfare, we determined population structure, genotype distribution, and likelihood of cross-fertilization during coinfection and also investigated the extent of naturally occurring antigenic diversity for the E . tenella AMA1 homolog. Using genome-wide Sequenom SNP-based haplotyping, targeted sequencing, and single-cell genotyping, we show that in this coccidian the functionality of Et AMA1 appears to outweigh immune evasion. This result is in direct contrast to the situation in Plasmodium and most likely is underpinned by the biology of the direct and acute coccidian life cycle in the definitive host.

• Publisher: National Acad Sciences,National Academy of Sciences
• Subject: Animals / Antigenic Variation / Antigens / Antigens, Protozoan - immunology / Apicomplexa / Base Sequence / Biological Sciences / Chickens - parasitology / Coccidiosis - parasitology / Cross-fertilization / Crosses, Genetic / Eimeria tenella / Eimeria tenella - genetics / Eimeria tenella - immunology / Epidemiology / Feces / Genetic Variation / Genetics / Genetics, Population / Genotype / Geography / Molecular Sequence Data / Oocysts / Parasites / Phylogeny / Plasmodium / Plasmodium - genetics / Plasmodium - immunology / PNAS Plus / Polymorphism / Polymorphism, Single Nucleotide / Population structure / Poultry Diseases - parasitology / Protozoan Vaccines / Toxoplasma gondii / Vaccines