title: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Registration is not required for observational studies.
  
  
  BACKGROUND
  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.forename: Enoch
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authors.lastname: Muyanja
authors.forename: Aloysius
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authors.forename: Glenda
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authors.forename: Jakub
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authors.lastname: Kopycinski
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authors.forename: Michaela J
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authors.lastname: Smith
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authors.lastname: Isern
authors.forename: Scott
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authors.lastname: Michael
authors.forename: Guido
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authors.lastname: Silvestri
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authors.lastname: Vanderford
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authors.forename: Giuseppe
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authors.lastname: Pantaleo
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authors.lastname: Gillmour
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authors.lastname: Kiwanuka
authors.forename: Annet
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authors.lastname: Nanvubya
authors.forename: Claudia
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authors.lastname: Schmidt
authors.forename: Josephine
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authors.lastname: Birungi
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: Patricia
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authors.lastname: Fast
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.forename: Lydie
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authors.lastname: Trautmann
authors.forename: Denis
authors.initials: D
authors.lastname: Gaucher
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007113:Immunity, Innate; D007117:Immunization, Secondary; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D013557:Switzerland; D014454:Uganda; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014779:Virus Replication / Q000276:immunology; D015004:Yellow Fever / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D022341:Yellow Fever Vaccine / Q000008:administration & dosage / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology / Q000502:physiology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D022341:Yellow Fever Vaccine