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 p estis 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 anti gens induced superior systemic and mucosal immunity in comparison with free F1 and V. All of the mice immunized with soluble antigens died s hot-try after an aerosol challenge consisting of 1 x 10(5) colony-form ing units of plague bacteria. In contrast 66% of the co-encapsulated s ubunit vaccinees survived this lethal challenge. Humoral immunity to p lague was improved further; resulting in 80% protection from challenge , if a relatively high dose (10 mu g) of cholera toxin B subunit was a dded to the microsphere suspension prior to intra-nasal delivery, Sign ificantly, by adding 10 mu g cholera toxin B subunit to the free antig en solution a 100% post-challenge survival rate was attained. We concl ude that in this animal model of pneumonic plague, intra-nasal adminis tration of microgram quantities of Yersinia pestis subunits confers pr otective immunity, provided the vaccines are microencapsulated or admi xed with a strong mucosal adjuvant, such as the cholera toxin B subuni t. (C) 1998 Elsevier Science Ltd. All rights reserved.