Analysis of local and systemic immunological responses after intra-tracheal, intra-nasal and intra-muscular administration of microsphere co-encapsulated Yersinia pestis sub-unit vaccines.
Intra-tracheal, intra-nasal and intra-muscular immunisation with admixed Y. pestis sub-units (3 micrograms V, 0.47 microgram F1) or equivalent doses of poly-L-lactide microsphere co-encapsulated antigens was done. Systemic and mucosal responses to F1 and V differed according to immunisation route, and encapsulated status of the sub-units. Irrespective of immunisation site, particulated sub-units stimulated statistically superior primary systemic reactions, with intra-tracheal and nasal microsphere immunisations eliciting superior serum anti-V IgG titres in comparison to intra-muscular injection of free vaccines (p < 0.001 beyond day 8). Pulmonary and nasal delivery of microspheres induced primary serum anti-V IgG titres which were greater (p < 0.039) or equal to (p > 0.056) those after intra-muscular injection of spheres. In terms of serum anti-F1 titres, mice responded best to intra-muscular, and comparatively poorly to intra-nasal immunisations. Intra-tracheal administration of microspheres induced strongest responses in the respiratory tract, dominated by the IgG rather than IgA isotype. An intra-nasal booster immunisation on day 63 potentiated strong local and circulating anti-V IgG titres in microsphere vaccinees. Priming and boosting with free vaccines induced significantly depressed secondary serum anti-F1 titres relative to microsphere immunisations (p < 0.024 at days 78 and 120). In contrast to other priming sites, intra-tracheal instillation of encapsulated vaccines facilitated the induction of IgG antibody to both F1 and V in day 146 broncho-alveolal washings. With the exception of primary responses to F1 in mice immunised intra-tracheally with microspheres, IgG1 was the dominant subclass of anti-F1/V IgG in serum. We conclude that introduction of biodegradable microspheres containing the F1 and V sub-units into to the upper or lower respiratory tract engenders immune responses of a magnitude comparable with that induced by parenteral immunisation, and may present a means of protecting individuals from plague.
Eyles
J E
JE
Department of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK.
Spiers
I D
ID
Williamson
E D
ED
Alpar
H O
HO
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D018893:Bronchoalveolar Lavage; D004797:Enzyme-Linked Immunosorbent Assay; D007273:Injections, Intramuscular; D051379:Mice; D008863:Microspheres; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D011322:Primary Prevention; D014132:Trachea; D015010:Yersinia pestis / Q000276:immunology*
D000907:Antibodies, Bacterial; D010931:Plague Vaccine