title: Host genetic factors and vaccine-induced immunity to hepatitis B virus infection.
abstract: BACKGROUND
  Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent carriage despite vaccination. We investigated the role of host genetic factors in long-term immunity against HBV infection based on peak anti-HBs level and seroconversion to anti-HBc.
  
  
  METHODS
  We analyzed 715 SNP across 133 candidate genes in 662 infant vaccinees from The Gambia, assessing peak vaccine-induced anti-HBs level and core antibody (anti-HBc) status, whilst adjusting for covariates. A replication study comprised 43 SNPs in a further 393 individuals.
  
  
  RESULTS
  In our initial screen we found variation in IFNG, MAPK8, and IL10RA to affect peak anti-HBs level (GMTratio of < 0.6 or > 1.5 and P < or = 0.001) and lesser associations in other genes. Odds of core-conversion was associated with variation in CD163. A coding change in ITGAL (R719V) with likely functional relevance showed evidence of association with increased peak anti-HBs level in both screens (1st screen: s595_22 GMTratio 1.71, P = 0.013; 2nd screen: s595_22 GMTratio 2.15, P = 0.011).
  
  
  CONCLUSIONS
  This is to our knowledge the largest study to date assessing genetic determinants of HBV vaccine-induced immunity. We report on associations with anti-HBs level, which is directly related to durability of antibody level and predictive of vaccine efficacy long-term. A coding change in ITGAL, which plays a central role in immune cell interaction, was shown to exert beneficial effects on induction of peak antibody level in response to HBV vaccination. Variation in this gene does not appear to have been studied in relation to immune responses to viral or vaccine challenges previously. Our findings suggest that genetic variation in loci other than the HLA region affect immunity induced by HBV vaccination.
authors: London School of Hygiene & Tropical Medicine, London, United Kingdom. branwen.hennig@lshtm.ac.uk
authors: Branwen J
authors: BJ
authors: Hennig
authors: Katherine
authors: K
authors: Fielding
authors: John
authors: J
authors: Broxholme
authors: Mathurin
authors: M
authors: Diatta
authors: Maimuna
authors: M
authors: Mendy
authors: Catrin
authors: C
authors: Moore
authors: Andrew J
authors: AJ
authors: Pollard
authors: Pura
authors: P
authors: Rayco-Solon
authors: Giorgio
authors: G
authors: Sirugo
authors: Marianne A
authors: MA
authors: van der Sande
authors: Pauline
authors: P
authors: Waight
authors: Hilton C
authors: HC
authors: Whittle
authors: Syed M
authors: SM
authors: Zaman
authors: Adrian V
authors: AV
authors: Hill
authors: Andrew J
authors: AJ
authors: Hall
mesh_terms: D006509:Hepatitis B / Q000235:genetics / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans
chemical_list: D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines