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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Host genetic factors and vaccine-induced immunity to hepatitis B virus infection
PLoS ONE, Volume 3, No. 3, Article e1898, Year 2008
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Description
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 vacination. 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≤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: s545_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. © 2008 Hennig et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2268746/bin/pone.0001898.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2268746/bin/pone.0001898.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2268746/bin/pone.0001898.s003.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2268746/bin/pone.0001898.s004.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2268746/bin/pone.0001898.s005.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2268746/bin/pone.0001898.s006.xls
Authors & Co-Authors
Hennig, Branwen J.W.
Unknown Affiliation
Fielding, Katherine Linda
Unknown Affiliation
Broxholme, John
Unknown Affiliation
Diatta, Mathurin A.
Unknown Affiliation
Mendy, Maimuna E.
Unknown Affiliation
Moore, Catrin E.
Unknown Affiliation
Pollard, Andrew J.
Unknown Affiliation
Rayco-Solon, Pura
Unknown Affiliation
Sirugo, G.
Unknown Affiliation
van der Sande, Marianne A.B.
Unknown Affiliation
Waight, Pauline A.
Unknown Affiliation
Whittle, Hilton C.
Unknown Affiliation
Zaman, Syed M.A.
Unknown Affiliation
Hill, Adrian V. S.
Unknown Affiliation
Hall, Andrew J.
Unknown Affiliation
Statistics
Citations: 86
Authors: 15
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pone.0001898
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Locations
Gambia