Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.

Schistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now...

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Main Authors: Juan U Rojo, Michael W Melkus, Kameswara Rao Kottapalli, Oscar E Okiya, Justin Sudduth, Weidong Zhang, Adebayo J Molehin, Darrick Carter, Afzal A Siddiqui
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5305113?pdf=render
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author Juan U Rojo
Michael W Melkus
Kameswara Rao Kottapalli
Oscar E Okiya
Justin Sudduth
Weidong Zhang
Adebayo J Molehin
Darrick Carter
Afzal A Siddiqui
author_facet Juan U Rojo
Michael W Melkus
Kameswara Rao Kottapalli
Oscar E Okiya
Justin Sudduth
Weidong Zhang
Adebayo J Molehin
Darrick Carter
Afzal A Siddiqui
author_sort Juan U Rojo
collection DOAJ
description Schistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now ready to move to clinical trials. In order to better assess Sm-p80 vaccine immunogenicity; here we used a systems biology approach employing RNA-sequencing to identify gene signatures and epistatic interactions following Sm-p80 vaccination in mouse and baboon models that may predict vaccine efficacy. Recombinant Sm-p80 + CpG-oligodeoxynucleotide (ODN) vaccine formulation induced both cellular and humoral immunity genes with a predominant TH1 response as well as TH2 and TH17 gene signatures. Early gene responses and gene-network interactions in mice immunized with rSm-p80 + ODN appear to be initiated through TLR4 signaling. CSF genes, S100A alarmin genes and TNFRSF genes appear to be a signature of vaccine immunogenicity/efficacy as identified by their participation in gene network interactions in both mice and baboons. These gene families may provide a basis for predicting desirable outcomes for vaccines against schistosomiasis leading to a better understanding of the immune system response to vaccination.
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spelling doaj.art-43276af558654fccb8e7e0a38ed3f1762022-12-22T00:19:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017167710.1371/journal.pone.0171677Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.Juan U RojoMichael W MelkusKameswara Rao KottapalliOscar E OkiyaJustin SudduthWeidong ZhangAdebayo J MolehinDarrick CarterAfzal A SiddiquiSchistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now ready to move to clinical trials. In order to better assess Sm-p80 vaccine immunogenicity; here we used a systems biology approach employing RNA-sequencing to identify gene signatures and epistatic interactions following Sm-p80 vaccination in mouse and baboon models that may predict vaccine efficacy. Recombinant Sm-p80 + CpG-oligodeoxynucleotide (ODN) vaccine formulation induced both cellular and humoral immunity genes with a predominant TH1 response as well as TH2 and TH17 gene signatures. Early gene responses and gene-network interactions in mice immunized with rSm-p80 + ODN appear to be initiated through TLR4 signaling. CSF genes, S100A alarmin genes and TNFRSF genes appear to be a signature of vaccine immunogenicity/efficacy as identified by their participation in gene network interactions in both mice and baboons. These gene families may provide a basis for predicting desirable outcomes for vaccines against schistosomiasis leading to a better understanding of the immune system response to vaccination.http://europepmc.org/articles/PMC5305113?pdf=render
spellingShingle Juan U Rojo
Michael W Melkus
Kameswara Rao Kottapalli
Oscar E Okiya
Justin Sudduth
Weidong Zhang
Adebayo J Molehin
Darrick Carter
Afzal A Siddiqui
Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.
PLoS ONE
title Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.
title_full Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.
title_fullStr Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.
title_full_unstemmed Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.
title_short Sm-p80-based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons.
title_sort sm p80 based schistosomiasis vaccine mediated epistatic interactions identified potential immune signatures for vaccine efficacy in mice and baboons
url http://europepmc.org/articles/PMC5305113?pdf=render
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