Journal article
Immune activation alters cellular and humoral responses to yellow fever 17D vaccine
The Journal of clinical investigation, v 124(7), pp 3147-3158
09 Jun 2014
PMID: 24911151
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background.
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.
Metrics
Details
- Title
- Immune activation alters cellular and humoral responses to yellow fever 17D vaccine
- Creators
- Enoch Muyanja - Uganda Virus Research InstituteAloysius Ssemaganda - Uganda Virus Research InstitutePearline Ngauv - Vaccine & Gene Therapy Institute of FloridaRafael Cubas - Vaccine & Gene Therapy Institute of FloridaHelene Perrin - Vaccine & Gene Therapy Institute of FloridaDivya Srinivasan - Vaccine & Gene Therapy Institute of FloridaGlenda Canderan - Vaccine & Gene Therapy Institute of FloridaBenton Lawson - Emory UniversityJakub Kopycinski - International AIDS Vaccine InitiativeAmanda S. Graham - Florida Gulf Coast UniversityDawne K. Rowe - Florida Gulf Coast UniversityMichaela J. Smith - Florida Gulf Coast UniversitySharon Isern - Florida Gulf Coast UniversityScott Michael - Florida Gulf Coast UniversityGuido Silvestri - Emory UniversityThomas H. Vanderford - Emory UniversityErika Castro - University of LausanneGiuseppe Pantaleo - University of LausanneJoel Singer - HIV Legal NetworkJill Gillmour - International AIDS Vaccine InitiativeNoah Kiwanuka - Makerere UniversityAnnet Nanvubya - Uganda Virus Research InstituteClaudia Schmidt - International AIDS Vaccine InitiativeJosephine Birungi - Uganda Virus Research InstituteJosephine Cox - International AIDS Vaccine InitiativeElias K. Haddad - Florida Gulf Coast UniversityPontiano Kaleebu - Medical Research CouncilPatricia Fast - International AIDS Vaccine InitiativeRafick-Pierre Sekaly - Vaccine & Gene Therapy Institute of FloridaLydie Trautmann - Vaccine & Gene Therapy Institute of Florida
- Publication Details
- The Journal of clinical investigation, v 124(7), pp 3147-3158
- Publisher
- American Society for Clinical Investigation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000338688400037
- Scopus ID
- 2-s2.0-84907528075
- Other Identifier
- 991020099212404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental