Immune activation alters cellular and humoral responses to yellow fever 17D vaccine
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2014-06-09
Date Acceptance
2014-04-24
Citation
Journal of Clinical Investigation, 2014, 124 (7), pp.3147-3158
ISSN
1558-8238
Publisher
American Society for Clinical Investigation
Start Page
3147
End Page
3158
Journal / Book Title
Journal of Clinical Investigation
Volume
124
Issue
7
Copyright Statement
© 2014, The American Society for Clinical Investigation.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/24911151
Subjects
Adaptive Immunity Adult Antibodies, Neutralizing/blood Antibodies, Viral/blood B-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Cohort Studies Female Humans Immunity, Cellular Immunity, Humoral Immunity, Innate Immunization, Secondary Lymphocyte Activation Male Middle Aged Monocytes/immunology Switzerland Uganda Vaccines, Attenuated/administration & dosage/immunology Virus Replication/immunology Yellow Fever/*immunology/*prevention & control/virology Yellow Fever Vaccine/administration & dosage/*immunology Yellow fever virus/immunology/physiology Young Adult
Notes
Muyanja, Enoch Ssemaganda, Aloysius Ngauv, Pearline Cubas, Rafael Perrin, Helene Srinivasan, Divya Canderan, Glenda Lawson, Benton Kopycinski, Jakub Graham, Amanda S Rowe, Dawne K Smith, Michaela J Isern, Sharon Michael, Scott Silvestri, Guido Vanderford, Thomas H Castro, Erika Pantaleo, Giuseppe Singer, Joel Gillmour, Jill Kiwanuka, Noah Nanvubya, Annet Schmidt, Claudia Birungi, Josephine Cox, Josephine Haddad, Elias K Kaleebu, Pontiano Fast, Patricia Sekaly, Rafick-Pierre Trautmann, Lydie eng P30 AI050409/AI/NIAID NIH HHS/ R01AI099210/AI/NIAID NIH HHS/ Canadian Institutes of Health Research/Canada Clinical Trial Comparative Study Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2014/06/10 06:00 J Clin Invest. 2014 Jul 1;124(7):3147-58. doi: 10.1172/JCI75429. Epub 2014 Jun 9. 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.
Publication Status
Published