The EG95 antigen of Echinococcus spp. contains positively selected amino acids, which may influence host specificity and vaccine efficacy.
Echinococcosis is a worldwide zoonotic parasitic disease of humans and various herbivorous domestic animals (intermediate hosts) transmitted by the contact with wild and domestic carnivores (definitive hosts), mainly foxes and dogs. Recently, a vaccine was developed showing high levels of protection against one parasite haplotype (G1) of Echinococcus granulosus, and its potential efficacy against distinct parasite variants or species is still unclear. Interestingly, the EG95 vaccine antigen is a secreted glycosylphosphatydilinositol (GPI)-anchored protein containing a fibronectin type III domain, which is ubiquitous in modular proteins involved in cell adhesion. EG95 is highly expressed in oncospheres, the parasite life cycle stage which actively invades the intermediate hosts. After amplifying and sequencing the complete CDS of 57 Echinococcus isolates belonging to 7 distinct species, we uncovered a large amount of genetic variability, which may influence protein folding. Two positively selected sites are outside the vaccine epitopes, but are predicted to alter protein conformation. Moreover, phylogenetic analyses indicate that EG95 isoform evolution is convergent with regard to the number of beta-sheets and alpha-helices. We conclude that having a variety of EG95 isoforms is adaptive for Echinococcus parasites, in terms of their ability to invade different hosts, and we propose that a mixture of isoforms could possibly maximize vaccine efficacy.
Haag
Karen Luisa
KL
Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. karen.haag@ufrgs.br
Gottstein
Bruno
B
Ayala
Francisco Jose
FJ
D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D018509:DNA, Helminth / Q000235:genetics; D004443:Echinococcosis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D004446:Echinococcus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D019143:Evolution, Molecular; D015801:Helminth Proteins / Q000235:genetics* / Q000276:immunology*; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D018510:RNA, Helminth / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D014612:Vaccines / Q000235:genetics* / Q000276:immunology*
D000947:Antigens, Helminth; D017931:DNA Primers; D018509:DNA, Helminth; C446034:EG95 protein, Echinococcus granulosus; C460870:EM95 protein, Echinococcus multilocularis; D015801:Helminth Proteins; D018510:RNA, Helminth; D012333:RNA, Messenger; D014612:Vaccines