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Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine

BACKGROUND: The T-cell mediated immune response plays a central role in the control of malaria after natural infection or vaccination. There is increasing evidence that T-cell responses are heterogeneous and that both the quality of the immune response and the balance between pro-inflammatory and re...

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Autores principales: Mwacharo, Jedidah, Dunachie, Susanna J., Kai, Oscar, Hill, Adrian V. S., Bejon, Philip, Fletcher, Helen A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792766/
https://www.ncbi.nlm.nih.gov/pubmed/20037644
http://dx.doi.org/10.1371/journal.pone.0008434
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author Mwacharo, Jedidah
Dunachie, Susanna J.
Kai, Oscar
Hill, Adrian V. S.
Bejon, Philip
Fletcher, Helen A.
author_facet Mwacharo, Jedidah
Dunachie, Susanna J.
Kai, Oscar
Hill, Adrian V. S.
Bejon, Philip
Fletcher, Helen A.
author_sort Mwacharo, Jedidah
collection PubMed
description BACKGROUND: The T-cell mediated immune response plays a central role in the control of malaria after natural infection or vaccination. There is increasing evidence that T-cell responses are heterogeneous and that both the quality of the immune response and the balance between pro-inflammatory and regulatory T-cells determines the outcome of an infection. As Malaria parasites have been shown to induce immunosuppressive responses to the parasite and non-related antigens this study examined T-cell mediated pro-inflammatory and regulatory immune responses induced by malaria vaccination in children in an endemic area to determine if these responses were associated with vaccine immunogenicity. METHODS: Using real–time RT- PCR we profiled the expression of a panel of key markers of immunogenecity at different time points after vaccination with two viral vector vaccines expressing the malaria TRAP antigen (FP9-TRAP and MVA-TRAP) or following rabies vaccination as a control. PRINCIPAL FINDINGS: The vaccine induced modest levels of IFN-γ mRNA one week after vaccination. There was also an increase in FoxP3 mRNA expression in both TRAP stimulated and media stimulated cells in the FFM ME-TRAP vaccine group; however, this may have been driven by natural exposure to parasite rather than by vaccination. CONCLUSION: Quantitative PCR is a useful method for evaluating vaccine induced cell mediated immune responses in frozen PBMC from children in a malaria endemic country. Future studies should seek to use vaccine vectors that increase the magnitude and quality of the IFN-γ immune response in naturally exposed populations and should monitor the induction of a regulatory T cell response.
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spelling pubmed-27927662009-12-24 Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine Mwacharo, Jedidah Dunachie, Susanna J. Kai, Oscar Hill, Adrian V. S. Bejon, Philip Fletcher, Helen A. PLoS One Research Article BACKGROUND: The T-cell mediated immune response plays a central role in the control of malaria after natural infection or vaccination. There is increasing evidence that T-cell responses are heterogeneous and that both the quality of the immune response and the balance between pro-inflammatory and regulatory T-cells determines the outcome of an infection. As Malaria parasites have been shown to induce immunosuppressive responses to the parasite and non-related antigens this study examined T-cell mediated pro-inflammatory and regulatory immune responses induced by malaria vaccination in children in an endemic area to determine if these responses were associated with vaccine immunogenicity. METHODS: Using real–time RT- PCR we profiled the expression of a panel of key markers of immunogenecity at different time points after vaccination with two viral vector vaccines expressing the malaria TRAP antigen (FP9-TRAP and MVA-TRAP) or following rabies vaccination as a control. PRINCIPAL FINDINGS: The vaccine induced modest levels of IFN-γ mRNA one week after vaccination. There was also an increase in FoxP3 mRNA expression in both TRAP stimulated and media stimulated cells in the FFM ME-TRAP vaccine group; however, this may have been driven by natural exposure to parasite rather than by vaccination. CONCLUSION: Quantitative PCR is a useful method for evaluating vaccine induced cell mediated immune responses in frozen PBMC from children in a malaria endemic country. Future studies should seek to use vaccine vectors that increase the magnitude and quality of the IFN-γ immune response in naturally exposed populations and should monitor the induction of a regulatory T cell response. Public Library of Science 2009-12-23 /pmc/articles/PMC2792766/ /pubmed/20037644 http://dx.doi.org/10.1371/journal.pone.0008434 Text en Mwacharo et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mwacharo, Jedidah
Dunachie, Susanna J.
Kai, Oscar
Hill, Adrian V. S.
Bejon, Philip
Fletcher, Helen A.
Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine
title Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine
title_full Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine
title_fullStr Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine
title_full_unstemmed Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine
title_short Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine
title_sort quantitative pcr evaluation of cellular immune responses in kenyan children vaccinated with a candidate malaria vaccine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792766/
https://www.ncbi.nlm.nih.gov/pubmed/20037644
http://dx.doi.org/10.1371/journal.pone.0008434
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