title: Enhancement of cytokine-driven NK cell IFN-γ production after vaccination of HCMV infected Africans.
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.
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.|MRC International Nutrition Group, Nutrition Theme, MRC Keneba, Cambridge, UK.
authors.forename: Alansana
authors.initials: A
authors.lastname: Darboe
authors.affiliation: MRC International Nutrition Group, Nutrition Theme, MRC Keneba, Cambridge, UK.
authors.forename: Ebrima
authors.initials: E
authors.lastname: Danso
authors.affiliation: Vaccine and Immunity Theme, Infant Immunology, Medical Research Council Unit The Gambia, Cambridge, UK.
authors.forename: Ed
authors.initials: E
authors.lastname: Clarke
authors.affiliation: Vaccine and Immunity Theme, Infant Immunology, Medical Research Council Unit The Gambia, Cambridge, UK.
authors.forename: Ama
authors.initials: A
authors.lastname: Umesi
authors.affiliation: Vaccine and Immunity Theme, Infant Immunology, Medical Research Council Unit The Gambia, Cambridge, UK.
authors.forename: Ebrima
authors.initials: E
authors.lastname: Touray
authors.affiliation: MRC International Nutrition Group, Nutrition Theme, MRC Keneba, Cambridge, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Wegmuller
authors.affiliation: MRC International Nutrition Group, Nutrition Theme, MRC Keneba, Cambridge, UK.|MRC Human Nutrition Research, Cambridge, UK.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Moore
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Martin R
authors.identifier: 0000-0002-1567-8389
authors.initials: MR
authors.lastname: Goodier
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa / Q000453:epidemiology; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000208:ethnology / Q000276:immunology* / Q000821:virology; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D023321:Poliovirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination; D064166:Vaccine Potency; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: C558158:DTPolio vaccine; D004168:Diphtheria Toxoid; C508017:IL2RA protein, human; D007252:Influenza Vaccines; D020382:Interleukin-18; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D052118:Lysosomal-Associated Membrane Protein 1; D023321:Poliovirus Vaccines; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: DTPiP vaccine; Influenza vaccine; NK cells; NKG2C; Vaccination