Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

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dc.contributor.authorMuyanja, Enoch
dc.contributor.authorSsemaganda, Aloysius
dc.contributor.authorNgauv, Pearline
dc.contributor.authorCubas, Rafael
dc.contributor.authorPerrin, Helene
dc.contributor.authorSrinivasan, Divya
dc.contributor.authorCanderan, Glenda
dc.contributor.authorLawson, Benton
dc.contributor.authorKopycinski, Jakub
dc.contributor.authorGraham, Amanda S.
dc.contributor.authorRowe, Dawne K.
dc.contributor.authorSmith, Michaela J.
dc.contributor.authorIsern, Sharon
dc.contributor.authorMichael, Scott
dc.contributor.authorSilvestri, Guido
dc.contributor.authorVanderford, Thomas H.
dc.contributor.authorCastro, Erika
dc.contributor.authorPantaleo, Giuseppe
dc.contributor.authorSinger, Joel
dc.contributor.authorGillmour, Jill
dc.contributor.authorKiwanuka, Noah
dc.contributor.authorNanvubya, Annet
dc.contributor.authorSchmidt, Claudia
dc.contributor.authorBirungi, Josephine
dc.contributor.authorCox, Josephine
dc.contributor.authorHaddad, Elias K.
dc.contributor.authorKaleebu, Pontiano
dc.contributor.authorFast, Patricia
dc.contributor.authorSekaly, Rafick-Pierre
dc.contributor.authorTrautmann, Lydie
dc.date.accessioned2018-08-06T11:15:23Z
dc.date.available2018-08-06T11:15:23Z
dc.date.issued2014-07
dc.descriptionThis study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort.en_US
dc.description.abstractBackground. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D–induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D–neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada’s Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.en_US
dc.identifier.citationMuyanja et al. Immune activation alters cellular and humoral responses to yellow fever 17D vaccine. The Journal of Clinical Investigation Vol. 124 No. 7 Pages 3147-3158 (July 2014) 3147–3158. DOI: 10.1172/JCI75429 http://www.jci.orgen_US
dc.identifier.urihttps://hdl.handle.net/20.500.11951/334
dc.language.isoenen_US
dc.publisherThe Journal of Clinical Investigationen_US
dc.subjectYellow fever 17D vaccineen_US
dc.subjectMalariaen_US
dc.subjectTuberculosisen_US
dc.subjectDengue virus infectionsen_US
dc.titleImmune activation alters cellular and humoral responses to yellow fever 17D vaccineen_US
dc.typeArticleen_US
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