title: Mucosal antibody responses are directed by viral burden in children with acute influenza infection.
abstract: BACKGROUND
  Influenza infection causes excess hospitalizations and deaths in younger patients, but susceptibility to severe disease is poorly understood. While mucosal antibodies can limit influenza-associated infection and disease, little is known about acute mucosal antibody responses to influenza infection.
  
  
  OBJECTIVE
  These studies characterize mucosal antiviral antibody production in children during lower respiratory infection (LRI) with H1N1 influenza versus other viral LRI and examine the relationship between mucosal antiviral antibodies and protection against severe disease.
  
  
  METHODS
  B lymphocytes were assessed by immunohistochemistry in lung tissue from infants with fatal acute seasonal influenza infection. Nasopharyngeal secretions (NPS) were obtained at presentation from children with acute respiratory illness, including H1N1 (2009) influenza infection. Total and antiviral antibodies, and inflammatory and immune mediators, were quantified by ELISA. Neutralizing activity in NPS was detected using a pseudotyped virus assay. Viral burden was assessed by qPCR.
  
  
  CONCLUSIONS
  B lymphocytes were abundant in lung tissue of infants with fatal acute influenza LRI. Among surviving children with H1N1 infection, only a small subset (11%) demonstrated H1N1 neutralizing activity in NPS. H1N1 neutralizing activity coincided with high local levels of antiviral IgM, IgG and IgA, greater detection of inflammatory mediators, and higher viral burden (P = 0·016). Patients with mucosal antiviral antibody responses demonstrated more severe respiratory symptoms including greater hypoxia (P = 0·0018) and pneumonia (P = 0·038). These patients also trended toward younger age, longer duration of illness and longer hospital stays. Prophylaxis strategies that heighten neutralizing antibody production in the mucosa are likely to benefit both older and younger children.
authors.affiliation: Food and Drug Administration, Center for Biologics Evaluation and Research, Bethesda, MD, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Afsheen
authors.initials: A
authors.lastname: Abid
authors.forename: Robert
authors.initials: R
authors.lastname: Fisher
authors.forename: Nancy
authors.initials: N
authors.lastname: Eller
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Mikolajczyk
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welliver
authors.forename: Aleta B
authors.initials: AB
authors.lastname: Bonner
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Scott
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reed
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007150:Immunohistochemistry; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology* / Q000821:virology; D008168:Lung / Q000166:cytology / Q000276:immunology; D008297:Male; D009092:Mucous Membrane / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D019562:Viral Load; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines