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Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.
J Clin Invest. 2014 Jul; 124(7):3147-58.JCI

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.

Authors

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Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
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.

Language

eng

PubMed ID

24911151

Citation

Muyanja, Enoch, et al. "Immune Activation Alters Cellular and Humoral Responses to Yellow Fever 17D Vaccine." The Journal of Clinical Investigation, vol. 124, no. 7, 2014, pp. 3147-58.
Muyanja E, Ssemaganda A, Ngauv P, et al. Immune activation alters cellular and humoral responses to yellow fever 17D vaccine. J Clin Invest. 2014;124(7):3147-58.
Muyanja, E., Ssemaganda, A., Ngauv, P., Cubas, R., Perrin, H., Srinivasan, D., Canderan, G., Lawson, B., Kopycinski, J., Graham, A. S., Rowe, D. K., Smith, M. J., Isern, S., Michael, S., Silvestri, G., Vanderford, T. H., Castro, E., Pantaleo, G., Singer, J., ... Gaucher, D. (2014). Immune activation alters cellular and humoral responses to yellow fever 17D vaccine. The Journal of Clinical Investigation, 124(7), 3147-58. https://doi.org/10.1172/JCI75429
Muyanja E, et al. Immune Activation Alters Cellular and Humoral Responses to Yellow Fever 17D Vaccine. J Clin Invest. 2014;124(7):3147-58. PubMed PMID: 24911151.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune activation alters cellular and humoral responses to yellow fever 17D vaccine. AU - Muyanja,Enoch, AU - Ssemaganda,Aloysius, AU - Ngauv,Pearline, AU - Cubas,Rafael, AU - Perrin,Helene, AU - Srinivasan,Divya, AU - Canderan,Glenda, AU - Lawson,Benton, AU - Kopycinski,Jakub, AU - Graham,Amanda S, AU - Rowe,Dawne K, AU - Smith,Michaela J, AU - Isern,Sharon, AU - Michael,Scott, AU - Silvestri,Guido, AU - Vanderford,Thomas H, AU - Castro,Erika, AU - Pantaleo,Giuseppe, AU - Singer,Joel, AU - Gillmour,Jill, AU - Kiwanuka,Noah, AU - Nanvubya,Annet, AU - Schmidt,Claudia, AU - Birungi,Josephine, AU - Cox,Josephine, AU - Haddad,Elias K, AU - Kaleebu,Pontiano, AU - Fast,Patricia, AU - Sekaly,Rafick-Pierre, AU - Trautmann,Lydie, AU - Gaucher,Denis, Y1 - 2014/06/09/ PY - 2014/01/28/received PY - 2014/04/24/accepted PY - 2014/6/10/entrez PY - 2014/6/10/pubmed PY - 2014/10/7/medline SP - 3147 EP - 58 JF - The Journal of clinical investigation JO - J Clin Invest VL - 124 IS - 7 N2 - 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. SN - 1558-8238 UR - https://www.unboundmedicine.com/medline/citation/24911151/Immune_activation_alters_cellular_and_humoral_responses_to_yellow_fever_17D_vaccine_ L2 - https://doi.org/10.1172/JCI75429 DB - PRIME DP - Unbound Medicine ER -