title: Sex-Differential Non-Vaccine-Specific Immunological Effects of Diphtheria-Tetanus-Pertussis and Measles Vaccination.
abstract: Vaccines can have nontargeted heterologous effects that manifest as increased protection against nonvaccine infections, as described for measles vaccine (MV), or increased susceptibility to infections and death, as described following diphtheria-tetanus-whole cell pertussis (DTP) vaccination. The mechanisms are unknown, and high-quality immunological studies are lacking. This study was designed to investigate the heterologous effects of MV and DTP in 302 Gambian infants. The results support a sex-differential immunosuppressive effect of DTP on innate proinflammatory responses and T-cell immunity. Males but not females receiving MV had enhanced proinflammatory innate responses. The results point to modified signaling via Toll-like receptor 4 (TLR4) as a possible mechanism for the effects on innate immunity. When both vaccines were administered together, purified protein derivative responses were enhanced in females but downregulated in males. Collectively, these data indicate immunological effects that could account for heterologous effects of MV and DTP, to take forward into prospective trials.
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Fatou
authors.initials: F
authors.lastname: Noho-Konteh
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Jane U
authors.initials: JU
authors.lastname: Adetifa
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Momodou
authors.initials: M
authors.lastname: Cox
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Safayet
authors.initials: S
authors.lastname: Hossin
authors.affiliation: Biostatistics Consulting Platform, Faculty of Medicine, Nursing and Health Sciences.
authors.forename: John
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: My Thanh
authors.initials: MT
authors.lastname: Le
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Lady Chilel
authors.initials: LC
authors.lastname: Sanyang
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Abdoulie
authors.initials: A
authors.lastname: Drammeh
authors.affiliation: Department of Immunology and Pathology Monash Institute of Medical Engineering, Monash University, Prahran, Victoria, Australia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
authors.affiliation: Division of Infection and Pathway Medicine, University of Edinburgh.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Forster
authors.affiliation: Division of Infection and Pathway Medicine, University of Edinburgh.
authors.forename: Paul
authors.initials: P
authors.lastname: Dickinson
authors.affiliation: Division of Infection and Pathway Medicine, University of Edinburgh.
authors.forename: Peter
authors.initials: P
authors.lastname: Ghazal
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia London School of Hygiene and Tropical Medicine.
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia Nuffield Department of Medicine, University of Oxford, United Kingdom.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Sutherland
authors.affiliation: Infant Immunology Group, Vaccines and Immunity Theme, Medical Research Council Unit, Fajara, The Gambia Department of Immunology and Pathology.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology*; D005260:Female; D005714:Gambia; D015894:Genome, Human; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007165:Immunosuppression Therapy; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008458:Measles Vaccine / Q000276:immunology*; D012313:RNA; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D007074:Immunoglobulin G; D008458:Measles Vaccine; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D012313:RNA
keywords: T cells; cytokines; heterologous effects; innate immunity; transcriptome