Therapeutic effect of preS2-containing vaccine in an infant infected with a vaccine-escape variant (Thr127) of hepatitis B virus

Abstract

A male baby born to HBV-infected mother received HBIG and vaccine (S-gene recombinant) according to the conventional protocol for prevention of vertical HBV transmission, but did not show active production of anti-HBs. Additional two shots of S-gene recombinant vaccines at months 9 and 12 also failed to induce antibody despite increased doses. Then, at months 14, 15, and 19, a preS2-containing vaccine was injected, followed by a prompt seroconversion to anti-HBs. Retrospective analyses of the baby's sera revealed that HBV DNA was repeatedly positive in this baby's sera throughout the period of time when anti-HBs antibody remained negative (months 6–15). Genetic analyses of HBV DNA from the mother and her baby showed that: (i) mother's HBV DNA was a mixture of adw and adr subtypes, whereas baby's HBV DNA consisted solely of adr subtype; and (ii) baby's HBV was a S-gene variant with its 127th codon coding for threonine instead of proline that is typical to wild type HBV/adr (Thr¹²⁷). Thus, it seems in this case that the Thr¹²⁷ mutant did escape conventional vaccines but could not escape preS2-induced immune response, and that eventually the preS2-containing vaccine worked as a therapeutic vaccine.