Intra nasal administration of poly-lactic acid microsphere co-encapsulated Yersinia pestis subunits confers protection from pneumonic plague in the mouse

Equivocal doses of soluble, or high molecular weight poly (lactic acid) microsphere co-encapsulated, F1 and V subunit antigens of Yersinia pestis were used to immunize mice intra-nasally. Animals were dosed on day 1 and 7 with 2.724 mu g V plus 0.956 mu g F1. Co-encapsulated antigens induced superior systemic and mucosal immunity in comparison with free F1 and V. All of the mice immunized with soluble antigens died shot-try after an aerosol challenge consisting of 1 x 10(5) colony-forming units of plague bacteria. In contrast 66% of the co-encapsulated subunit vaccinees survived this lethal challenge. Humoral immunity to plague was improved further; resulting in 80% protection from challenge, if a relatively high dose (10 mu g) of cholera toxin B subunit was added to the microsphere suspension prior to intra-nasal delivery, Significantly, by adding 10 mu g cholera toxin B subunit to the free antigen solution a 100% post-challenge survival rate was attained. We conclude that in this animal model of pneumonic plague, intra-nasal administration of microgram quantities of Yersinia pestis subunits confers protective immunity, provided the vaccines are microencapsulated or admixed with a strong mucosal adjuvant, such as the cholera toxin B subunit. (C) 1998 Elsevier Science Ltd. All rights reserved.