Immune activation alters cellular and humoral responses to yellow fever 17D vaccine
Autor: | Sharon Isern, Rafael Cubas, Josephine Birungi, Lydie Trautmann, Josephine H. Cox, C. Schmidt, Jill Gillmour, Divya Srinivasan, Pearline Ngauv, Enoch Muyanja, Elias K. Haddad, Rafick Pierre Sekaly, Guido Silvestri, Jakub Kopycinski, Erika Castro, Benton Lawson, Pontiano Kaleebu, Giuseppe Pantaleo, Dawne K. Rowe, Scott F. Michael, Glenda Canderan, Noah Kiwanuka, Thomas H. Vanderford, Aloysius Ssemaganda, Michaela J. Smith, Joel Singer, Amanda S. Graham, Helene Perrin, Patricia E. Fast, Denis Gaucher, Annet Nanvubya |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Adult
Male T cell Immunization Secondary Yellow fever vaccine Adaptive Immunity CD8-Positive T-Lymphocytes Antibodies Viral Lymphocyte Activation Vaccines Attenuated Virus Replication Monocytes Cohort Studies Young Adult Immune system Immunity Yellow Fever Medicine Humans Uganda B cell B-Lymphocytes Immunity Cellular business.industry Yellow Fever Vaccine General Medicine Middle Aged Acquired immune system Virology Antibodies Neutralizing Immunity Innate Immunity Humoral Vaccination medicine.anatomical_structure Immunology Female Clinical Medicine Yellow fever virus Corrigendum business CD8 Switzerland medicine.drug |
Popis: | 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. |
Databáze: | OpenAIRE |
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