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

BACKGROUND: 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...

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Autores principales: Norling, Martin, Bishop, Richard P., Pelle, Roger, Qi, Weihong, Henson, Sonal, Drábek, Elliott F., Tretina, Kyle, Odongo, David, Mwaura, Stephen, Njoroge, Thomas, Bongcam-Rudloff, Erik, Daubenberger, Claudia A., Silva, Joana C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583173/
https://www.ncbi.nlm.nih.gov/pubmed/26403690
http://dx.doi.org/10.1186/s12864-015-1910-9
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author Norling, Martin
Bishop, Richard P.
Pelle, Roger
Qi, Weihong
Henson, Sonal
Drábek, Elliott F.
Tretina, Kyle
Odongo, David
Mwaura, Stephen
Njoroge, Thomas
Bongcam-Rudloff, Erik
Daubenberger, Claudia A.
Silva, Joana C.
author_facet Norling, Martin
Bishop, Richard P.
Pelle, Roger
Qi, Weihong
Henson, Sonal
Drábek, Elliott F.
Tretina, Kyle
Odongo, David
Mwaura, Stephen
Njoroge, Thomas
Bongcam-Rudloff, Erik
Daubenberger, Claudia A.
Silva, Joana C.
author_sort Norling, Martin
collection PubMed
description BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1910-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-45831732015-09-26 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, Martin Bishop, Richard P. Pelle, Roger Qi, Weihong Henson, Sonal Drábek, Elliott F. Tretina, Kyle Odongo, David Mwaura, Stephen Njoroge, Thomas Bongcam-Rudloff, Erik Daubenberger, Claudia A. Silva, Joana C. BMC Genomics Research Article BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1910-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-24 /pmc/articles/PMC4583173/ /pubmed/26403690 http://dx.doi.org/10.1186/s12864-015-1910-9 Text en © Norling et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Norling, Martin
Bishop, Richard P.
Pelle, Roger
Qi, Weihong
Henson, Sonal
Drábek, Elliott F.
Tretina, Kyle
Odongo, David
Mwaura, Stephen
Njoroge, Thomas
Bongcam-Rudloff, Erik
Daubenberger, Claudia 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
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_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_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_sort genomes of three stocks comprising the most widely utilized live sporozoite theileria parva vaccine exhibit very different degrees and patterns of sequence divergence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583173/
https://www.ncbi.nlm.nih.gov/pubmed/26403690
http://dx.doi.org/10.1186/s12864-015-1910-9
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