ANALYSIS OF LOCAL AND SYSTEMIC IMMUNOLOGICAL RESPONSES AFTER INTRA-TRACHEAL, INTRANASAL AND INTRA-MUSCULAR ADMINISTRATION OF MICROSPHERE CO-ENCAPSULATED YERSINIA-PESTIS SUBUNIT VACCINES

Intra-tracheal, intra-nasal and intra-muscular immunisation with admix ed Y. pestis sub-units (3 mu g V, 0.47 mu g F1) or equivalent doses of poly-L-lactide microsphere co-encapsulated antigens was done. Systemi c and mucosal responses to F1 and V differed according to immunisation route, and encapsulated status of the sub-units. Irrespective of immu nisation site, particulated sub-units stimulated statistically superio r primary systemic reactions, with intra-tracheal and nasal microspher e immunisations eliciting superior serum anti-V IgG titres in comparis on to intra-muscular injection of free vaccines (p<0.001 beyond day 8) . Pulmonary and nasal delivery of microspheres induced primary serum a nti-V IgG titres which were greater (p<0.039) or equal to (p>0.056) th ose after intra-muscular injection of spheres. In terms of serum anti- F1 titres, mice responded best to intra-muscular, and comparatively po orly to intra-nasal immunisations. Intra-tracheal administration of mi crospheres induced strongest responses in the respiratory tract, domin ated by IgG rather than IgA isotope. An intra-nasal booster immunisati on on day 63 potentiated strong local and circulating anti-V IgG titre s in microsphere vaccinees. Priming and boosting with free vaccines in duced significantly depressed secondary serum anti-F1 titres relative to microspheres immunisations (p<0.024 at days 78 and 120). In contras t to other priming sites, intratracheal instillation of encapsulated v accines facilitated the induction of IgG antibody to both F1 and V in day 146 broncho-alveolal washings. With the exception of primary respo nses to F1 in mice immunised intra-tracheally with microspheres, IgG(i ) was the dominant subclass of anti-F1/V IgG in serum. We conclude tha t introduction of biodegradable microspheres containing the F1 and V s ub-units into to the upper or lower respiratory tract engenders immune responses of a magnitude comparable with that induced by parenteral i mmunisation, and may present a means of protecting individuals from pl ague. (C) 1998 Elsevier Science Ltd. All rights reserved.