AIM: Hepatitis B surface antigen (HBsAg) mutant of hepatitis B virus (HBV) is one of the important factors that result in immune escape and cause failure of immunization. In this study we reported and characterized a novel HBV mutant with A-to-G at nt551 and intended to provide theoretical data for prevention of HBV infection in China. METHODS: A methodology comprising polymerase chain reaction (PCR) amplifying, M13 bacteriophage cloning and nucleotide sequencing was used to analyze the sera of the pediatric patient who was hepatitis B (HB) immune failure. Expression plasmids containing the mutant S gene and a wild-type (adr) S gene were constructed respectively and the recombinant HBsAg were expressed in COS-7 cells under the regulation of SV40 early promoter. The recombinant proteins were investigated for their immunological reactivity with different monoclonal antibodies (mAb) against "a" determinant and vaccine-raised human neutralizing antibodies. RESULTS: It was found that there was a new point mutation at nt551 of the HBV (adr) genome from A to G, leading to a substitution of methionine (Met) to valine (Val) at position 133 in the "a" determinant of HBsAg. Compared to the wild-type HBsAg, the binding activity of the mutant HBsAg to mAbs (A6, A11 and S17) and to vaccine-raised human anti-hepatitis B surface antibody (anti-HBs) decreased significantly. CONCLUSION: According to the facts that the patient has been immunized with HB vaccine and that the serum is anti-HBs positive and HBsAg negative, and based on the nucleotide sequence analysis of the mutant HBV S gene and its alteration of antigenicity, the HBV is considered to be a new vaccine-induced immune escape mutant different from the known ones.
AIM: Hepatitis B surface antigen (HBsAg) mutant of hepatitis B virus (HBV) is one of the important factors that result in immune escape and cause failure of immunization. In this study we reported and characterized a novel HBV mutant with A-to-G at nt551 and intended to provide theoretical data for prevention of HBV infection in China. METHODS: A methodology comprising polymerase chain reaction (PCR) amplifying, M13 bacteriophage cloning and nucleotide sequencing was used to analyze the sera of the pediatric patient who was hepatitis B (HB) immune failure. Expression plasmids containing the mutant S gene and a wild-type (adr) S gene were constructed respectively and the recombinant HBsAg were expressed in COS-7 cells under the regulation of SV40 early promoter. The recombinant proteins were investigated for their immunological reactivity with different monoclonal antibodies (mAb) against "a" determinant and vaccine-raised human neutralizing antibodies. RESULTS: It was found that there was a new point mutation at nt551 of the HBV (adr) genome from A to G, leading to a substitution of methionine (Met) to valine (Val) at position 133 in the "a" determinant of HBsAg. Compared to the wild-type HBsAg, the binding activity of the mutant HBsAg to mAbs (A6, A11 and S17) and to vaccine-raised human anti-hepatitis B surface antibody (anti-HBs) decreased significantly. CONCLUSION: According to the facts that the patient has been immunized with HB vaccine and that the serum is anti-HBs positive and HBsAg negative, and based on the nucleotide sequence analysis of the mutant HBV S gene and its alteration of antigenicity, the HBV is considered to be a new vaccine-induced immune escape mutant different from the known ones.
Authors: S Seddigh-Tonekaboni; J A Waters; S Jeffers; R Gehrke; B Ofenloch; A Horsch; G Hess; H C Thomas; P Karayiannis Journal: J Med Virol Date: 2000-02 Impact factor: 2.327
Authors: T Shinji; N Koide; T Hanafusa; H Hada; T Oka; N Takayama; H Shiraha; M Nakamura; K Ujike; Y Yumoto; T Tsuji Journal: Hepatogastroenterology Date: 1998 Mar-Apr
Authors: X Y Wang; T J Harrison; X He; Q Y Chen; G J Li; M H Liu; H Li; J Y Yang; Z L Fang Journal: Epidemiol Infect Date: 2015-04-23 Impact factor: 4.434