Publication: Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model
Issued Date
2015-09-29
Resource Type
ISSN
18732518
0264410X
0264410X
Other identifier(s)
2-s2.0-84941811406
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Mahidol University
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SCOPUS
Bibliographic Citation
Vaccine. Vol.33, No.40 (2015), 5321-5331
Suggested Citation
Susanna Dunachie, Tamara Berthoud, Adrian V.S. Hill, Helen A. Fletcher Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model. Vaccine. Vol.33, No.40 (2015), 5321-5331. doi:10.1016/j.vaccine.2015.07.087 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35378
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Title
Transcriptional changes induced by candidate malaria vaccines and correlation with protection against malaria in a human challenge model
Abstract
© 2015 The Authors. 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.