Although the vast surface area occupied by mucosal membranes (400m2 in humans) infers susceptibility to pathogenic entities in the external milieu, parenteral modes of immunisation are generally ineffectual in terms of protecting these sites with neutralising antibodies [ I ] . A prerequisite for the induction of specific antibodies of the secretory IgA (sIgA) isotype at mucosae, is delivery of vaccine to IgA-inductive lymphoid compartments such as GALT [2, 31. Fortuitously, the intestinal epithelium is not completely impermeable to the passage of macromolecules and particles which access GALT, and systemic compartments, via M-cells and other uptake mechanisms. Most orally administered antigens, are however, ineffective immunogens because of their lumenal degradation and poor absorption into GALT. One approach is to encapsulate antigenic molecules. Microsphere encapsulation both protects antigen from lumenal degradation, and enhances uptake. Furthermore, conversion of soluble antigen into particulate species confers adjuvanticity [4]. The existence of a common mucosal immune system dictates that successful delivery of vaccine to GALT may ultimately result in the concomitant production of specific sIgA at a variety of anatomically disparate mucosal membranes [5]. Oral immunisation offers the added advantage that some degree of systemic immunity can be induced alongside peripheral mucosal responses [2-5, 61. Protein subunits of Y. pestis have the ability to protect animals against injected challenge with virulent strains of the bacterium. Fraction 1 (FI) (MW 17.5 Kd) is the major protein component of the Y. pestis capsule, whilst the V antigen (MW 37 Kd) is a secreted regulatory protein and / or virulence factor [7]. The pneumonic form of plague is transmissible via airborne droplets, and thus a need for effective mucosal vaccination procedures exists. In this study we have investigated immunological responses in mice following oral administration of free and PLA microsphere encapsulated F1 and V antigens. A modified double emulsion-solvent evaporation technique [8] was employcd for subunit encapsulation. This involved emulsification of an aqueous solution of antigen into polymer (PLA2Kd and PLA100Kd in the case of F1 and V respectively) dissolved in dichloromethane. The resultant water in oil product was further emulsified into an external aqueous phase containing polyvinyl alcohol. Microspheres were harvested by centrifugation at 15000g, and lyophilised. Antigen loading was determined with the bicinchonic protein assay [9]. Particle sizing was achieved using laser diffractometry. Formulated F1 and V microspheres had mean diameters of 3.1 and 6.0 pm respectively. Antigen loading was 0.34 (Fl) and 0.13 (V) % wlw. Prepared microspheres were administered orally to two groups of Balblc mice (n=2). Each animal received 100 pg of microencapsulated F1 or V suspended in 0.4 ml of 3 % NaHC03 on day 1. 3 and 28. Equivocal doses of free antigen were administered orally as a control (n=3). Periodically, serum was analysed using an ELISA for evidence of specific antiF1 / V IgG induction. The proliferative activity of splenic T cells from treated animals, following exposure to antigen in vitro, was investigated on day 170 [ lo] . Cultured PP derived cells were used in a modified ELISA designed to quantify local antibody production. A phasic systemic response resulted from oral administration of free and encapsulated F1 and V subunits (Fig 1.). Relative to free, IgG titres were elevated in mice immunised with encapsulated antigen, consistent with the thesis that microencapsulation may adjuvantise antigenic material and / or facilitate its translocation to systemic compartments. Relative anti-F1 and V IgA titres were found to be significantly higher in cells cultured from PP excised from mice treated with microsphere encapsulated subunits as opposed to free antigen (Fig. 2).