Enhancement of cytokine-driven NK cell IFN-γ production after vaccination of HCMV infected Africans

Alansana Darboe, Ebrima Danso, Ed Clarke, Ama Umesi, Ebrima Touray, Rita Wegmuller, Sophie E. Moore, Eleanor M Riley, Martin R. Goodier

Research output: Contribution to journalArticlepeer-review

Abstract

Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK-cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure. In contrast to populations with lower prevalence of HCMV infection, no significant enhancement of NK-cell responses (IFN-γ, CD107a, CD25) occurred after in vitro re-stimulation of post-vaccination NK cells with TIV or DTPiP antigens compared to pre-vaccination baseline cells. However, both vaccinations resulted in higher frequencies of NK cells producing IFN-γ in response to exogenous IL-12 with IL-18, which persisted for up to 6 months. Enhanced cytokine responsiveness was restricted to less differentiated NK cells, with increased frequencies of IFN-γ+cells observed within CD56brightCD57-, CD56dimCD57-NKG2C-and CD56dimCD57-NKG2C+NK-cell subsets. These data suggest a common mechanism whereby different vaccines enhance NK cell IFN-γ function in HCMV infected donors and raise the potential for further exploitation of NK cell "pre-activation" to improve vaccine effectiveness.

Original languageEnglish
Pages (from-to)1040-1050
Number of pages11
JournalEuropean Journal of Immunology
Volume47
Issue number6
Early online date6 Apr 2017
DOIs
Publication statusPublished - Jun 2017

Keywords

  • Adolescent
  • Adult
  • Africa
  • Aged
  • Child
  • Child, Preschool
  • Cytomegalovirus
  • Cytomegalovirus Infections
  • Diphtheria Toxoid
  • Female
  • Humans
  • Immunization, Secondary
  • Influenza Vaccines
  • Interferon-gamma
  • Interleukin-12
  • Interleukin-18
  • Interleukin-2 Receptor alpha Subunit
  • Interleukins
  • Killer Cells, Natural
  • Lysosomal-Associated Membrane Protein 1
  • Male
  • Middle Aged
  • Poliovirus Vaccines
  • Tetanus Toxoid
  • Vaccination
  • Vaccine Potency
  • Vaccines, Combined
  • Young Adult
  • Journal Article
  • Research Support, Non-U.S. Gov't

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