The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence

Abstract

BackgroundThere are no commercially available vaccines against human protozoan parasitic diseases, despite the success of vaccination-induced long-term protection against infectious diseases. East Coast fever, caused by the protist Theileria parva, kills one million cattle each year in sub-Saharan Africa, and contributes significantly to hunger and poverty in the region. A highly effective, live, multi-isolate vaccine against T. parva exists, but its component isolates have not been characterized. Here we sequence and compare the three component T. parva stocks within this vaccine, the Muguga Cocktail, namely Muguga, Kiambu5 and Serengeti-transformed, aiming to identify genomic features that contribute to vaccine efficacy.ResultsWe find that Serengeti-transformed, originally isolated from the wildlife carrier, the African Cape buffalo, is remarkably and unexpectedly similar to the Muguga isolate. The 420 detectable non-synonymous SNPs were distributed among only 53 genes, primarily subtelomeric antigens and antigenic families. The Kiambu5 isolate is considerably more divergent, with close to 40,000 SNPs relative to Muguga, including >8,500 non-synonymous mutations distributed among >1,700 (42.5 %) of the predicted genes. These genetic markers of the component stocks can be used to characterize the composition of new batches of the Muguga Cocktail.ConclusionsDifferences among these three isolates, while extensive, represent only a small proportion of the genetic variation in the entire species. Given the efficacy of the Muguga Cocktail in inducing long-lasting protection against infections in the field, our results suggest that whole-organism vaccines against parasitic diseases can be highly efficacious despite considerable genome-wide differences relative to the isolates against which they protect.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1910-9) contains supplementary material, which is available to authorized users.

Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions

“…A recent study by Lemieux and colleagues56, released while this article was under review, suggests that all non-R1 isolates sequenced here likely belong to a New England lineage of B. microti separate from that containing the R1 reference. Second, non-R1 specific mutations, and differences in gene expression among isolates, are significantly associated with chromosome ends, a pattern similar to the accumulation of new mutations documented in other apicomplexans5758. Finally, much of the non-synonymous variation identified among isolates falls disproportionately in a small number of genes, including many members of the secretome, suggestive of immune system-related selective pressure.…”

A review of recent research on Theileria parva : Implications for the infection and treatment vaccination method for control of East Coast fever

“…The ability of Serengeti to induce a carrier state has never been investigated. Although, as already mentioned, very similar to T. parva Muguga, Serengeti does contain 53 loci with non‐synonymous SNPS relative to the T. parva Muguga reference genome at certain highly polymorphic loci (Norling et al., ). There had been no application of Muguga cocktail ITM vaccination anywhere in Kenya at the time this study was performed.…”

Approaches to vaccination against Theileria parva and Theileria annulata

“…52 These findings are consistent with sequencing data on parasite genes encoding two polymorphic antigens (Tp1 and Tp2) and genomewide SNP density, which revealed much greater genotypic diversity in parasites isolated from buffalo compared with those of cattle origin. 54 The results of two recent studies of the Muguga cocktail vaccine, one involving genomic sequencing of the three component parasites 55 and the other based on high-throughput sequencing of PCR amplicons of six genes encoding T. parva antigens (including Tp1 and Tp2), 56 have indicated that the vaccine contains only a small component of the genetic and antigenic diversity detected in field populations of T. parva. Each of the three parasite isolates in the Muguga cocktail exhibited very limited diversity, and two of them (Muguga and Serengeti) showed a remarkably high level of sequence similarity, but differed significantly from the third isolate (Kiambu).…”

“…109 The impact of genome size variations on parasite gene content and biology, however, remains to be fully documented. Such data are beginning to accumulate for T. parva as more strains are sequenced 55,110,111 and their impact on genotypic diversity has been briefly reviewed elsewhere. 31 Both genomes exhibit a highly compact structure.…”