Vaccination of chronic hepatitis B virus carriers with preS2/S envelope protein is not associated with the emergence of envelope escape mutants

PreS2/S vaccination of chronic hepatitis B virus (HBV) carriers led to a re duction in HBV replication or clearance of virus in 30% of treated patients . This study assessed whether vaccinotherapy of chronic HBV carriers induce d the selection of escape mutants in the envelope 'a' determinant and wheth er envelope genetic variability might affect the response to vaccination. N o amino acid differences were observed in the 'a' determinant between seque nces obtained before and after treatment (five responders and seven nonresp onders). However, alignment with HBV prototype sequences revealed seven ami no acid changes. Two mutations (T140S and P127L) diverged from subtype vari ations. In the complete envelope sequence (five non-responders and five res ponders), ten amino acid modifications were detected between sequences obta ined before and after treatment. The absence of any common mutations did no t enable the definition of a hot spot of mutations implicated in the respon se to vaccination. Moreover, vaccinotherapy does not induce the selection o f escape mutants in the 'a' determinant.