Host genetic factors and vaccine-induced immunity to hepatitis B virus infection.


Hennig, BJ; Fielding, K; Broxholme, J; Diatta, M; Mendy, M; Moore, C; Pollard, AJ; Rayco-Solon, P; Sirugo, G; van der Sande, MA; Waight, P; Whittle, HC; Zaman, SM; Hill, AV; Hall, AJ; (2008) Host genetic factors and vaccine-induced immunity to hepatitis B virus infection. PLoS One, 3 (3). e1898. ISSN 1932-6203 DOI: 10.1371/journal.pone.0001898

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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). CONCLUSION: 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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Tropical Epidemiology Group
Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 18365030
Web of Science ID: 260762400036
URI: http://researchonline.lshtm.ac.uk/id/eprint/8080

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