Referee 2's Review:

This is an extensive association study of 715 genomewide SNP with peak anti-HBs values after HBsAg vaccination and anti-HBc conversion in a large population of Gambian infants. Significant asociation from a first screen regarding peak anti-HBs levels were asessed in a second screen. The stuy encompasses a very large population of well characterized Gambian infant vaccinees It is one of the largest studies on this subject up to now. Only few stuis have investigated immunogenetic factors other than HLA-antigens (polymophisms).

However, there are a number of problems with the paper:
1. As stated above, the paper investigate the association of SNPs with peak anti-HBs titers and not durable vaccine induced immunity as suggested in the title. Peak anti-HBs titers are the key determinant of antibody persistence. Other determinans are natural reboostering due to contact with the HBV virus. The paper does not convince me that there are genetic factors that detrmine the durability of the vaccine response. The read out are aniti-HBs titres. The authors did not investigate the association of the rate of decay of anti-HBs with SNPs.

2 The investigated population is very heterogeneous largely due to vaccination schedule and distinct vaccines used. This appears to be the major determinant of the observed variation although the authors apply statistical modells to correct for this type of variation. However, it would be very interesting for the reader to get an estimate of the strength of influence of an individual SNP (e.g. the identified ITGAL SNP) in comparison to the importance of the vaccine schedule.

3. All anti-HBc positive vaccinees were investigated with age matched controls in the 1st screen. No anti-HBc positive patients were investigated in the second screen. As the breakthrough infections (the authors group vacinees that developed chronic hepatitis together with vaccinees that only seroconverted to anti-HBc) might very well have a genetic background, this grouping induces a considerable bias and could account for the lach of reproducibility of the findings in the second screen.

4. Were all vaccinees investigated for HBsAg and anti-HBc before vacination?

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.