Lack of in vitro lymphoproliferative response to hepatitis B surface antigen in healthy vaccine recipients

A majority of HBsAg vaccine recipients show good anti-HBs antibody responses but poor antigen specific lymphoproliferative responses. We investigated the basis for this poor in vitro antigen specific proliferative responsiveness in vaccinees who had received the standard three dose schedule (0, 1 and 6 months) of plasma derived HBsAg vaccine. Peripheral blood mononuclear cells (PBMC) from 26 of 29 (89.7%) vaccinees failed to show lymphoproliferative responses to HBsAg in spite of having a very good anti-HBs antibody response (geometric mean titre 3154 IU/1). The mitogen (phytohaemagglutinin, PHA) and antigen (purified protein derivative, PPD) driven lymphoproliferative responses in these individuals were normal. Addition of exogenous recombinant interleukin-2 (rIL-2) along with HBsAg had no effect in the response to HBsAg in six of nine vaccinees, who were tested six months after the third vaccine dose or in four unvaccinated controls. However, in three vaccinees who did not have lymphoproliferative response to HBsAg alone, addition of exogenous rIL-2 resulted in a synergistic response. These data suggest that HBsAg reactive cells are few in the peripheral circulation of a majority of individuals following the standard three dose schedule of vaccination and addition of exogenous rIL-2 induces a response only in a subgroup of individuals. The inability of HBsAg to induce a T cell proliferative response may have implications for the maintenance of protective immunity and immunological memory following vaccination.