Dataset Information

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

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.

SUBMITTER: Muyanja E

PROVIDER: S-EPMC4071376 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Muyanja Enoch E Ssemaganda Aloysius A Ngauv Pearline P Cubas Rafael R Perrin Helene H Srinivasan Divya D Canderan Glenda G Lawson Benton B Kopycinski Jakub J Graham Amanda S AS Rowe Dawne K DK Smith Michaela J MJ Isern Sharon S Michael Scott S Silvestri Guido G Vanderford Thomas H TH Castro Erika E Pantaleo Giuseppe G Singer Joel J Gillmour Jill J Kiwanuka Noah N Nanvubya Annet A Schmidt Claudia C Birungi Josephine J Cox Josephine J Haddad Elias K EK Kaleebu Pontiano P Fast Patricia P Sekaly Rafick-Pierre RP Trautmann Lydie L Gaucher Denis D

The Journal of clinical investigation 20140609 7

<h4>Background</h4>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.<h4>Methods</h4>We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 v ...[more]

PMID: 24911151

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Project description:The non-human primate (NHP) model (specifically rhesus and cynomolgus macaques) has facilitated our understanding of the pathogenic mechanisms of yellow fever (YF) disease and allowed evaluation of safety and efficacy of YF-17D vaccines. However, the accuracy of this model in mimicking vaccine-induced immunity in humans remains to be fully determined. We used a system biology approach to compare hematological, biochemical, transcriptomic, innate and antibody-mediated immune responses in cynomolgus macaques and human participants following YF-17D vaccination. Immune response progression in cynomolgus macaques followed a similar course as in adult humans, but with slightly earlier onset. Yellow fever virus neutralizing antibody responses occurred earlier in cynomolgus macaques (by Day 7 [D7]), but titers >10 were reached in both species by D14 post-vaccination and were not significantly different by D28 (PRNT50 titers 3.6 Log vs 3.5 Log in cynomolgus macaques and human participants, respectively; p = 0.821). Changes in neutrophils, NK cells, monocytes, T and B cell frequency were higher in cynomolgus macaques and persisted for four weeks versus less than two weeks in humans. Low levels of systemic inflammatory cytokines (IL-1Ra, IL-8, MIP-1α, IP-10, MCP-1 or VEGF) were detected in either or both species, but with no or only slight changes versus baseline. Similar changes in gene expression profiles were elicited in both species. These included enriched and up-regulated type I IFN-associated viral sensing, antiviral innate response, and dendritic cell activation pathways D3–D7 post-vaccination in both species. Hematological and blood biochemical parameters remained relatively unchanged versus baseline in both species. Low level YF-17D viremia (RNAemia) was transiently detected in some cynomolgus macaques (28% [5/18]) but generally absent in humans (except one participant [5%; 1/20]). Importance: Cynomolgus macaques were confirmed as a valid surrogate model for replicating YF-17D vaccine-induced responses in humans, and suggest a key role for type I IFN.

Dataset Information

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

Background

Methods

Results

Conclusion

Trial registration

Funding

Publications

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

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