title: Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by hemagglutination inhibition and virus microneutralization assays in a cohort of seroconverting adults in Singapore.
abstract: BACKGROUND
  The rate of decline of antibody titers to influenza following infection can affect results of serological surveys, and may explain re-infection and recurrent epidemics by the same strain.
  
  
  METHODS
  We followed up a cohort who seroconverted on hemagglutination inhibition (HI) antibody titers (≥ 4-fold increase) to pandemic influenza A(H1N1)pdm09 during a seroincidence study in 2009. Along with the pre-epidemic sample, and the sample from 2009 with the highest HI titer between August and October 2009 (A), two additional blood samples obtained in April 2010 and September 2010 (B and C) were assayed for antibodies to A(H1N1)pdm09 by both HI and virus microneutralization (MN) assays. We analyzed pair-wise mean-fold change in titers and the proportion with HI titers ≥ 40 and MN ≥ 160 (which correlated with a HI titer of 40 in our assays) at the 3 time-points following seroconversion.
  
  
  RESULTS
  A total of 67 participants contributed 3 samples each. From the highest HI titer in 2009 to the last sample in 2010, 2 participants showed increase in titers (by HI and MN), while 63 (94%) and 49 (73%) had reduction in HI and MN titers, respectively. Titers by both assays decreased significantly; while 70.8% and 72.3% of subjects had titers of ≥ 40 and 160 by HI and MN in 2009, these percentages decreased to 13.9% and 36.9% by September 2010. In 6 participants aged 55 years and older, the decrease was significantly greater than in those aged below 55, so that none of the elderly had HI titers ≥ 40 nor MN titers ≥ 160 by the final sample. Due to this decline in titers, only 23 (35%) of the 65 participants who seroconverted on HI in sample A were found to seroconvert between the pre-epidemic sample and sample C, compared to 53 (90%) of the 59 who seroconverted on MN on Sample A.
  
  
  CONCLUSIONS
  We observed marked reduction in titers 1 year after seroconversion by HI, and to a lesser extent by MN. Our findings have implications for re-infections, recurrent epidemics, vaccination strategies, and for cohort studies measuring infection rates by seroconversion.
authors: Jung Pu
authors: JP
authors: Hsu
authors: Xiahong
authors: X
authors: Zhao
authors: Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, 16 Medical Drive, Kent Ridge, 117597 Singapore, Singapore. mark.chen.ic@gmail.com.
authors: Mark I-Cheng
authors: MI
authors: Chen
authors: Alex R
authors: AR
authors: Cook
authors: Vernon
authors: V
authors: Lee
authors: Wei Yen
authors: WY
authors: Lim
authors: Linda
authors: L
authors: Tan
authors: Ian G
authors: IG
authors: Barr
authors: Lili
authors: L
authors: Jiang
authors: Chyi Lin
authors: CL
authors: Tan
authors: Meng Chee
authors: MC
authors: Phoon
authors: Lin
authors: L
authors: Cui
authors: Raymond
authors: R
authors: Lin
authors: Yee Sin
authors: YS
authors: Leo
authors: Vincent T
authors: VT
authors: Chow
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D012846:Singapore / Q000453:epidemiology; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral