title: Immuno-epidemiologic correlates of pandemic H1N1 surveillance observations: higher antibody and lower cell-mediated immune responses with advanced age.
abstract: BACKGROUND
  Pandemic H1N1 (pH1N1) surveillance data showed lower attack rates but higher risk of severe outcomes with advanced age. We explored immuno-epidemiologic correlates of surveillance findings including humoral and cell-mediated immunity (CMI).
  
  
  METHODS
  In an age-based design, ∼100 banked/residual sera per 10-year age stratum were assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays for preexisting antibody to pH1N1 and recent seasonal H1N1 and H3N2 strains. In a separate birth cohort design defined by childhood influenza A/subtype priming (1919-1929: H1N1; 1945-1949: H1N1; 1958-1960: H2N2; 1969-1970: H3N2; 1978-1989: H3N2/H1N1), whole blood was collected from up to 50 volunteers per birth cohort. The ratio of Th1(IFN-γ):Th2(IL-10) cytokine responses was evaluated in vitro.
  
  
  RESULTS
  Antibody to seasonal viruses was highest in school-age children. Cross-reactive HI/MN antibody to pH1N1 was low among participants <70 years of age (yoa; 6%/4% ≥ 40), but seroprevalence increased at 70-79 yoa (27%/6%), increased even more at 80-89 yoa (65%/47%), and was highest at ≥90 yoa (88%/76%). CMI to pH1N1 was evident in all 5 birth cohorts but was lower compared with seasonal strains. There was little differentiation by subtype priming, but the Th1:Th2 ratio for all viruses dropped significantly in the 2 oldest cohorts.
  
  
  CONCLUSIONS
  Preexisting antibody may have protected the very old from pH1N1 infection, while diminished CMI may have contributed to greater severity once infected. In the young, cross-reactive pH1N1 antibody was mostly absent, while more intact CMI may have protected against severe outcomes.
authors.affiliation: British Columbia Centre for Disease Control, Vancouver, BC, V5Z 4R4, Canada. danuta.skowronski@bccdc.ca
authors.forename: Danuta M
authors.initials: DM
authors.lastname: Skowronski
authors.forename: Travis S
authors.initials: TS
authors.lastname: Hottes
authors.forename: Janet E
authors.initials: JE
authors.lastname: McElhaney
authors.forename: Naveed Z
authors.initials: NZ
authors.lastname: Janjua
authors.forename: Suzana
authors.initials: S
authors.lastname: Sabaiduc
authors.forename: Tracy
authors.initials: T
authors.lastname: Chan
authors.forename: Beth
authors.initials: B
authors.lastname: Gentleman
authors.forename: Dale
authors.initials: D
authors.lastname: Purych
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gardy
authors.forename: David M
authors.initials: DM
authors.lastname: Patrick
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
authors.forename: Gaston
authors.initials: G
authors.lastname: De Serres
authors.forename: Martin
authors.initials: M
authors.lastname: Petric
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053121:Influenza A Virus, H2N2 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D058873:Pandemics; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral