Protection studies following bronchopulmonary and intramuscular immunisation with Yersinia pestis F1 and V subunit vaccines coencapsulated in biodegradable microspheres: a comparison of efficacy

We have compared the ability of intramuscularly and intratracheally adminis tered recombinant F1 and V subunit antigens to safeguard mice from a lethal systemic challenge with plague. The combined subunits (1 mu g V plus 5 mu g F1) were inoculated either in the 'free' state as a solution, or entrappe d within microspheres composed of a biodegradable polyester (Poly-L-lactide ), on day 1 and 60 of the experiment. In comparison to the other regimens, introduction of microsphere suspensions into the respiratory tract resulted in statistically elevated levels of specific immunoglobulins in day 82 lun g wash samples. A subcutaneous challenge with virulent Yersinia pestis bact eria on day 137, equivalent to more than 10(5) mouse LD(50)s, was comparati vely well tolerated by all subunit treatment groups (with survival rates be tween 66 and 90%). In contrast, 80% of the mice injected intramuscularly wi th soluble F1 and V were defeated by a 10(7) MLD50 subcutaneous challenge, whereas the group immunised intramuscularly with microparticles were signif icantly better protected (p < 0.1) with 50% survival. Similarly, mice immun ised intratracheally with microparticles were significantly better safeguar ded (56% survival) compared with the group immunised with soluble subunits intramuscularly (p < 0.01). Soluble sub-units delivered intratracheally aff orded 33% protection against 10(7) MLD(50)s These data indicate that bronch opulmonary administration of microsphere co-encapsulated recombinant F1 and V antigens elicits a similar level of protective immunity against systemic plague infection as that evoked by injecting co-encapsulated subunits into the muscle. Such findings corroborate the thesis that introduction of appr opriately formulated F1 and V subunits into the respiratory tract may be an alternative to parenteral immunisation schedules for protecting individual s from plague. (C) 2000 Elsevier Science Ltd. All rights reserved.