Immunization with DNA, adenovirus or both in biodegradable alginate microspheres: effect of route of inoculation on immune response

To determine the potential for biodegradable alginate microspheres to be us ed as a delivery vehicle for DNA based vaccines, we constructed a plasmid, pMNe-gal-SV40, containing the bacterial P-galactosidase (LacZ) gene under t he control of the murine cytomegalovirus (MCMV) immediate-early promoter an d the simian virus 40 (SV40) polyadenylation signal. The effect of the rout e of administration and co-administration of adenovirus on systemic and muc osal immune responses were investigated. Mice were inoculated orally, intra nasally (i.n.), intramuscularly (i.m,), subcutaneously (s.c.) or intraperit oneally (i.p.) on days 0, 14 and 28 with microspheres containing plasmid DN A, bovine adenovirus type 3 (BAd3) or plasmid DNA + BAd3. Systemic routes o f immunization (i.m., s.c, and i.p.) resulted in higher LacZ- or BAd3-speci fic IgG ELISA titers compared to those obtained by mucosal routes of inocul ation (oral and i.n.). Mucosal immunization led to slightly higher titers o f LacZ- or BAd3-specific IgA at mucosal sites compared to those obtained by the various systemic routes. All the routes of immunization induced LacZ-s pecific lymphoproliferation. Co-administration of BAd3 enhanced the LacZ-sp ecific IgG response irrespective of the route of administration. (C) 2000 E lsevier Science Ltd. All rights reserved.