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

Abstract

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 micrograms V plus 0.956 micrograms 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 shortly 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 micrograms) of cholera toxin B subunit was added to the microsphere suspension prior to intra-nasal delivery. Significantly, by adding 10 micrograms 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.