title: Human newborn bacille Calmette-Guérin vaccination and risk of tuberculosis disease: a case-control study.
abstract: BACKGROUND
  An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette-Guérin (BCG) vaccination.
  
  
  METHODS
  In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls).
  
  
  RESULTS
  Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays.
  
  
  CONCLUSIONS
  Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development.
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Fletcher
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Filali-Mouhim
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Elisa
authors.initials: E
authors.lastname: Nemes
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Anthony
authors.initials: A
authors.lastname: Hawkridge
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Alana
authors.initials: A
authors.lastname: Keyser
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Samuel
authors.initials: S
authors.lastname: Njikan
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Brian
authors.initials: B
authors.lastname: Abel
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Kagina
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Ashley
authors.initials: A
authors.lastname: Veldsman
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética, Sede de Investigación Universitaria, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Nancy Marín
authors.initials: NM
authors.lastname: Agudelo
authors.affiliation: Public Health Research Institute, Rutgers Biomedical and Health Sciences, Newark, NJ, USA.
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Rafick-Pierre
authors.initials: RP
authors.lastname: Sekaly
authors.affiliation: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa. willem.hanekom@gatesfoundation.org.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000009:adverse effects*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine
keywords: Correlates of risk; Systems biology; Tuberculosis; Vaccine