Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A

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dc.contributor.authorTanner, Rachel
dc.contributor.authorKakalacheva, Kristina
dc.contributor.authorMiller, Ellen
dc.contributor.authorPathan, Ansar A
dc.contributor.authorChalk, Rod
dc.contributor.authorSander, Clare R
dc.contributor.authorScriba, Tom
dc.contributor.authorTameris, Michelle
dc.contributor.authorHawkridge, Tony
dc.contributor.authorMahomed, Hassan
dc.contributor.authorHussey, Greg
dc.contributor.authorHanekom, Willem
dc.contributor.authorCheckley, Anna
dc.contributor.authorMcShane, Helen
dc.contributor.authorFletcher, Helen A
dc.date.accessioned2015-07-30T04:00:50Z
dc.date.available2015-07-30T04:00:50Z
dc.date.issued2014-12-03
dc.date.updated2015-01-15T17:55:22Z
dc.description.abstractAbstract Background There is an urgent need for improved vaccines to protect against tuberculosis. The currently available vaccine Bacille Calmette-Guerin (BCG) has varying immunogenicity and efficacy across different populations for reasons not clearly understood. MVA85A is a modified vaccinia virus expressing antigen 85A from Mycobacterium tuberculosis which has been in clinical development since 2002 as a candidate vaccine to boost BCG-induced protection. A recent efficacy trial in South African infants failed to demonstrate enhancement of protection over BCG alone. The immunogenicity was lower than that seen in UK trials. The enzyme Indoleamine 2,3-dioxygenase (IDO) catalyses the first and rate-limiting step in the breakdown of the essential amino acid tryptophan. T cells are dependent on tryptophan and IDO activity suppresses T-cell proliferation and function. Methods Using samples collected during phase I trials with MVA85A across the UK and South Africa we have investigated the relationship between vaccine immunogenicity and IDO using IFN-γ ELISPOT, qPCR and liquid chromatography mass spectrometry. Results We demonstrate an IFN-γ dependent increase in IDO mRNA expression in peripheral blood mononuclear cells (PBMC) following MVA85A vaccination in UK subjects. IDO mRNA correlates positively with the IFN-γ ELISPOT response indicating that vaccine specific induction of IDO in PBMC is unlikely to limit the development of vaccine specific immunity. IDO activity in the serum of volunteers from the UK and South Africa was also assessed. There was no change in serum IDO activity following MVA85A vaccination. However, we observed higher baseline IDO activity in South African volunteers when compared to UK volunteers. In both UK and South African serum samples, baseline IDO activity negatively correlated with vaccine-specific IFN-γ responses, suggesting that IDO activity may impair the generation of a CD4+ T cell memory response. Conclusions Baseline IDO activity was higher in South African volunteers when compared to UK volunteers, which may represent a potential mechanism for the observed variation in vaccine immunogenicity in South African and UK populations and may have important implications for future vaccination strategies. Trial registration Trials are registered at ClinicalTrials.gov; UK cohort NCT00427830 , UK LTBI cohort NCT00456183 , South African cohort NCT00460590 , South African LTBI cohort NCT00480558 .
dc.identifier.apacitationTanner, R., Kakalacheva, K., Miller, E., Pathan, A. A., Chalk, R., Sander, C. R., ... Fletcher, H. A. (2014). Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/13611en_ZA
dc.identifier.chicagocitationTanner, Rachel, Kristina Kakalacheva, Ellen Miller, Ansar A Pathan, Rod Chalk, Clare R Sander, Tom Scriba, et al "Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A." <i>BMC Infectious Diseases</i> (2014) http://hdl.handle.net/11427/13611en_ZA
dc.identifier.citationTanner, R., Kakalacheva, K., Miller, E., Pathan, A. A., Chalk, R., Sander, C. R., ... & Fletcher, H. A. (2014). Serum indoleamine 2, 3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A. BMC infectious diseases, 14(1), 660.
dc.identifier.ris TY - Journal Article AU - Tanner, Rachel AU - Kakalacheva, Kristina AU - Miller, Ellen AU - Pathan, Ansar A AU - Chalk, Rod AU - Sander, Clare R AU - Scriba, Tom AU - Tameris, Michelle AU - Hawkridge, Tony AU - Mahomed, Hassan AU - Hussey, Greg AU - Hanekom, Willem AU - Checkley, Anna AU - McShane, Helen AU - Fletcher, Helen A AB - Abstract Background There is an urgent need for improved vaccines to protect against tuberculosis. The currently available vaccine Bacille Calmette-Guerin (BCG) has varying immunogenicity and efficacy across different populations for reasons not clearly understood. MVA85A is a modified vaccinia virus expressing antigen 85A from Mycobacterium tuberculosis which has been in clinical development since 2002 as a candidate vaccine to boost BCG-induced protection. A recent efficacy trial in South African infants failed to demonstrate enhancement of protection over BCG alone. The immunogenicity was lower than that seen in UK trials. The enzyme Indoleamine 2,3-dioxygenase (IDO) catalyses the first and rate-limiting step in the breakdown of the essential amino acid tryptophan. T cells are dependent on tryptophan and IDO activity suppresses T-cell proliferation and function. Methods Using samples collected during phase I trials with MVA85A across the UK and South Africa we have investigated the relationship between vaccine immunogenicity and IDO using IFN-γ ELISPOT, qPCR and liquid chromatography mass spectrometry. Results We demonstrate an IFN-γ dependent increase in IDO mRNA expression in peripheral blood mononuclear cells (PBMC) following MVA85A vaccination in UK subjects. IDO mRNA correlates positively with the IFN-γ ELISPOT response indicating that vaccine specific induction of IDO in PBMC is unlikely to limit the development of vaccine specific immunity. IDO activity in the serum of volunteers from the UK and South Africa was also assessed. There was no change in serum IDO activity following MVA85A vaccination. However, we observed higher baseline IDO activity in South African volunteers when compared to UK volunteers. In both UK and South African serum samples, baseline IDO activity negatively correlated with vaccine-specific IFN-γ responses, suggesting that IDO activity may impair the generation of a CD4+ T cell memory response. Conclusions Baseline IDO activity was higher in South African volunteers when compared to UK volunteers, which may represent a potential mechanism for the observed variation in vaccine immunogenicity in South African and UK populations and may have important implications for future vaccination strategies. Trial registration Trials are registered at ClinicalTrials.gov; UK cohort NCT00427830 , UK LTBI cohort NCT00456183 , South African cohort NCT00460590 , South African LTBI cohort NCT00480558 . DA - 2014-12-03 DB - OpenUCT DO - 10.1186/s12879-014-0660-7 DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A TI - Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A UR - http://hdl.handle.net/11427/13611 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13611
dc.identifier.urihttp://dx.doi.org/10.1186/s12879-014-0660-7
dc.identifier.vancouvercitationTanner R, Kakalacheva K, Miller E, Pathan AA, Chalk R, Sander CR, et al. Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A. BMC Infectious Diseases. 2014; http://hdl.handle.net/11427/13611.en_ZA
dc.language.rfc3066en
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License*
dc.rights.holderTanner et al.; licensee BioMed Central Ltd.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0*
dc.sourceBMC Infectious Diseasesen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcinfectdis/
dc.subject.otherIndoleamine 2,3-dioxygenaseen_ZA
dc.subject.otherTryptophanen_ZA
dc.subject.otherKynurenineen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherVaccineen_ZA
dc.subject.otherMVA85Aen_ZA
dc.subject.otherBCGen_ZA
dc.subject.otherInterferon-γen_ZA
dc.subject.otherLC-MSen_ZA
dc.titleSerum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A
dc.typeJournal Articleen_ZA
uct.type.filetype
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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