Modulation of the immune response to tetanus toxoid by polylactide-polyglycolide microspheres.

The cellular and antibody responses in mice to tetanus toxoid (TT), alone or adsorbed to aluminium hydroxide TT were compared to those obtained with TT incorporated in polylactide-polyglycolide (PLGA) microspheres, a candidate single dose vaccine. After subcutaneous injection, the serum IgM antibody to TT followed similar overall patterns for all preparations although the highest levels were achieved with the alum-adsorbed material. A similar pattern was observed with the overall IgG antibody responses. The isotype distribution of antibodies was broadly similar for all types of preparation although considerable qualitative differences were observed. IgG1 antibodies predominated although IgG2a and IgG2b made a substantial contribution, especially at three months in the case of the two adjuvanted preparations. The IgG3 responses to each type of vaccine were very low. Both alum and microsphere vaccines induced proliferative responses to TT in splenic lymphocytes at three months after vaccination. Each type of vaccine was much less effective in inducing proliferative responses in lymph node cells. There was evidence of induction of IL2, IL4 and interferon-gamma genes by microsphere vaccines in splenic but not lymph node cells. There were indications that PLGA microspheres alone exerted a modulating effect on cellular responses after immunization. These results suggest that TT encapsulated in microspheres induces a pattern of cellular and antibody responses qualitatively similar to those induced by conventional TT vaccines.