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

There 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. We 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. Differences 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.

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Main Authors: Norling, M., Bishop, Richard P., Pelle, Roger, Weihong Qi, Henson, S., Drábek, E.F., Tretina, Kyle, Odongo, D., Mwaura, S., Njoroge, T., Bongcam-Rudloff, E., Daubenberger, C.A., Silva, Joana C.
Format: Journal Article biblioteca
Language:English
Published: Springer 2015-12
Subjects:animal diseases, genetics, biotechnology,
Online Access:https://hdl.handle.net/10568/69467
https://doi.org/10.1186/s12864-015-1910-9
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spelling dig-cgspace-10568-694672023-12-08T19:36:04Z The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence Norling, M. Bishop, Richard P. Pelle, Roger Weihong Qi Henson, S. Drábek, E.F. Tretina, Kyle Odongo, D. Mwaura, S. Njoroge, T. Bongcam-Rudloff, E. Daubenberger, C.A. Silva, Joana C. animal diseases genetics biotechnology There 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. We 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. Differences 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. 2015-12 2016-01-05T17:41:12Z 2016-01-05T17:41:12Z Journal Article Norling, M., Bishop, R.P., Pelle, R., Weihong Qi, Henson, S., Drábek, E.F., Tretina, K., Odongo, D., Mwaura, S., Njoroge, T., Bongcam-Rudloff, E., Daubenberger, C.A. and Silva, J.C. 2016. The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence. BMC Genomics 16:729. 1471-2164 https://hdl.handle.net/10568/69467 https://doi.org/10.1186/s12864-015-1910-9 en CC-BY-4.0 Open Access Springer BMC Genomics
institution CGIAR
collection DSpace
country Francia
countrycode FR
component Bibliográfico
access En linea
databasecode dig-cgspace
tag biblioteca
region Europa del Oeste
libraryname Biblioteca del CGIAR
language English
topic animal diseases
genetics
biotechnology
animal diseases
genetics
biotechnology
spellingShingle animal diseases
genetics
biotechnology
animal diseases
genetics
biotechnology
Norling, M.
Bishop, Richard P.
Pelle, Roger
Weihong Qi
Henson, S.
Drábek, E.F.
Tretina, Kyle
Odongo, D.
Mwaura, S.
Njoroge, T.
Bongcam-Rudloff, E.
Daubenberger, C.A.
Silva, Joana C.
The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
description There 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. We 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. Differences 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.
format Journal Article
topic_facet animal diseases
genetics
biotechnology
author Norling, M.
Bishop, Richard P.
Pelle, Roger
Weihong Qi
Henson, S.
Drábek, E.F.
Tretina, Kyle
Odongo, D.
Mwaura, S.
Njoroge, T.
Bongcam-Rudloff, E.
Daubenberger, C.A.
Silva, Joana C.
author_facet Norling, M.
Bishop, Richard P.
Pelle, Roger
Weihong Qi
Henson, S.
Drábek, E.F.
Tretina, Kyle
Odongo, D.
Mwaura, S.
Njoroge, T.
Bongcam-Rudloff, E.
Daubenberger, C.A.
Silva, Joana C.
author_sort Norling, M.
title The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
title_short The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
title_full The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
title_fullStr The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
title_full_unstemmed The genomes of three stocks comprising the most widely utilized live sporozoite Theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
title_sort genomes of three stocks comprising the most widely utilized live sporozoite theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
publisher Springer
publishDate 2015-12
url https://hdl.handle.net/10568/69467
https://doi.org/10.1186/s12864-015-1910-9
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