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Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model
INTRODUCTION: The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and est...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582771/ https://www.ncbi.nlm.nih.gov/pubmed/26256523 http://dx.doi.org/10.1016/j.vaccine.2015.07.087 |
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author | Dunachie, Susanna Berthoud, Tamara Hill, Adrian V.S. Fletcher, Helen A. |
author_facet | Dunachie, Susanna Berthoud, Tamara Hill, Adrian V.S. Fletcher, Helen A. |
author_sort | Dunachie, Susanna |
collection | PubMed |
description | INTRODUCTION: The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and estimation of vaccine efficacy in the field. We have previously reported complete or partial efficacy against experimental sporozoite challenge by several vaccine regimens in healthy malaria-naïve subjects in Oxford. These include a prime-boost regimen with RTS,S/AS02A and modified vaccinia virus Ankara (MVA) expressing the CSP antigen, and a DNA-prime, MVA-boost regimen expressing the ME TRAP antigens. Using samples from these trials we performed transcriptional profiling, allowing a global assessment of responses to vaccination. METHODS: We used Human RefSeq8 Bead Chips from Illumina to examine gene expression using PBMC (peripheral blood mononuclear cells) from 16 human volunteers. To focus on antigen-specific changes, comparisons were made between PBMC stimulated with CSP or TRAP peptide pools and unstimulated PBMC post vaccination. We then correlated gene expression with protection against malaria in a human Plasmodium falciparum malaria challenge model. RESULTS: Differentially expressed genes induced by both vaccine regimens were predominantly in the IFN-γ pathway. Gene set enrichment analysis revealed antigen-specific effects on genes associated with IFN induction and proteasome modules after vaccination. Genes associated with IFN induction and antigen presentation modules were positively enriched in subjects with complete protection from malaria challenge, while genes associated with haemopoietic stem cells, regulatory monocytes and the myeloid lineage modules were negatively enriched in protected subjects. CONCLUSIONS: These results represent novel insights into the immune repertoires involved in malaria vaccination. |
format | Online Article Text |
id | pubmed-4582771 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45827712015-10-27 Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model Dunachie, Susanna Berthoud, Tamara Hill, Adrian V.S. Fletcher, Helen A. Vaccine Article INTRODUCTION: The complexity of immunity to malaria is well known, and clear correlates of protection against malaria have not been established. A better understanding of immune markers induced by candidate malaria vaccines would greatly enhance vaccine development, immunogenicity monitoring and estimation of vaccine efficacy in the field. We have previously reported complete or partial efficacy against experimental sporozoite challenge by several vaccine regimens in healthy malaria-naïve subjects in Oxford. These include a prime-boost regimen with RTS,S/AS02A and modified vaccinia virus Ankara (MVA) expressing the CSP antigen, and a DNA-prime, MVA-boost regimen expressing the ME TRAP antigens. Using samples from these trials we performed transcriptional profiling, allowing a global assessment of responses to vaccination. METHODS: We used Human RefSeq8 Bead Chips from Illumina to examine gene expression using PBMC (peripheral blood mononuclear cells) from 16 human volunteers. To focus on antigen-specific changes, comparisons were made between PBMC stimulated with CSP or TRAP peptide pools and unstimulated PBMC post vaccination. We then correlated gene expression with protection against malaria in a human Plasmodium falciparum malaria challenge model. RESULTS: Differentially expressed genes induced by both vaccine regimens were predominantly in the IFN-γ pathway. Gene set enrichment analysis revealed antigen-specific effects on genes associated with IFN induction and proteasome modules after vaccination. Genes associated with IFN induction and antigen presentation modules were positively enriched in subjects with complete protection from malaria challenge, while genes associated with haemopoietic stem cells, regulatory monocytes and the myeloid lineage modules were negatively enriched in protected subjects. CONCLUSIONS: These results represent novel insights into the immune repertoires involved in malaria vaccination. Elsevier Science 2015-09-29 /pmc/articles/PMC4582771/ /pubmed/26256523 http://dx.doi.org/10.1016/j.vaccine.2015.07.087 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Dunachie, Susanna Berthoud, Tamara Hill, Adrian V.S. Fletcher, Helen A. Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model |
title | Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model |
title_full | Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model |
title_fullStr | Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model |
title_full_unstemmed | Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model |
title_short | Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model |
title_sort | transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582771/ https://www.ncbi.nlm.nih.gov/pubmed/26256523 http://dx.doi.org/10.1016/j.vaccine.2015.07.087 |
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