The candidate TB vaccine, MVA85A, induces highly durable Th1 responses

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dc.contributor.authorTameris, Micheleen_ZA
dc.contributor.authorGeldenhuys, Hennieen_ZA
dc.contributor.authorLuabeya, Angelique KanyKanyen_ZA
dc.contributor.authorSmit, Ericaen_ZA
dc.contributor.authorHughes, Jane Een_ZA
dc.contributor.authorVermaak, Samanthaen_ZA
dc.contributor.authorHanekom, Willem Aen_ZA
dc.contributor.authorHatherill, Marken_ZA
dc.contributor.authorMahomed, Hassanen_ZA
dc.contributor.authorMcShane, Helenen_ZA
dc.contributor.authorScriba,Thomas Jen_ZA
dc.date.accessioned2016-01-11T06:52:07Z
dc.date.available2016-01-11T06:52:07Z
dc.date.issued2014en_ZA
dc.description.abstractBACKGROUND: Vaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis ( M.tb ). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone. METHODS: We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011. RESULTS: Of 252 potential participants, 183 (72.6%) consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA−CCR7+ central memory or CD45RA−CCR7− effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination. CONCLUSION: MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants.en_ZA
dc.identifier.apacitationTameris, M., Geldenhuys, H., Luabeya, A. K., Smit, E., Hughes, J. E., Vermaak, S., ... (2014). The candidate TB vaccine, MVA85A, induces highly durable Th1 responses. <i>PLoS One</i>, http://hdl.handle.net/11427/16257en_ZA
dc.identifier.chicagocitationTameris, Michele, Hennie Geldenhuys, Angelique KanyKany Luabeya, Erica Smit, Jane E Hughes, Samantha Vermaak, Willem A Hanekom, et al "The candidate TB vaccine, MVA85A, induces highly durable Th1 responses." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16257en_ZA
dc.identifier.citationameris, M., Geldenhuys, H., Luabeya, A. K., Smit, E., Hughes, J. E., Vermaak, S., ... & Scriba, T. J. (2014). The candidate TB vaccine, MVA85A, induces highly durable Th1 responses. PLoS ONE, 9, 87340. doi:10.1371/journal.pone.0087340en_ZA
dc.identifier.ris TY - Journal Article AU - Tameris, Michele AU - Geldenhuys, Hennie AU - Luabeya, Angelique KanyKany AU - Smit, Erica AU - Hughes, Jane E AU - Vermaak, Samantha AU - Hanekom, Willem A AU - Hatherill, Mark AU - Mahomed, Hassan AU - McShane, Helen AU - Scriba,Thomas J AB - BACKGROUND: Vaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis ( M.tb ). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone. METHODS: We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011. RESULTS: Of 252 potential participants, 183 (72.6%) consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA−CCR7+ central memory or CD45RA−CCR7− effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination. CONCLUSION: MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0087340 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - The candidate TB vaccine, MVA85A, induces highly durable Th1 responses TI - The candidate TB vaccine, MVA85A, induces highly durable Th1 responses UR - http://hdl.handle.net/11427/16257 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16257
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0087340
dc.identifier.vancouvercitationTameris M, Geldenhuys H, Luabeya AK, Smit E, Hughes JE, Vermaak S, et al. The candidate TB vaccine, MVA85A, induces highly durable Th1 responses. PLoS One. 2014; http://hdl.handle.net/11427/16257.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentSouth African Tuberculosis Vaccine Initiative (SATVI)en_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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Tameris et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherVaccination and immunizationen_ZA
dc.subject.otherInfantsen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherAdolescentsen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherMemory T cellsen_ZA
dc.titleThe candidate TB vaccine, MVA85A, induces highly durable Th1 responsesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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