Using a murine model, our objective is to optimize various formulations of our novel, univalent GBS vaccine and determine if they safely promote short and long term immunity and prevent vaginal colonization to multiple GBS serotypes.
C5a peptidase, a surface protein found on multiple serotypes of GBS, was microencapsulated in Poly lactide-co-glycolide acid (PLGA) using a water in oil in water double emulsion technique. 6-8 week old female ICR mice were vaccinated with 5 different formulations of vaccine: free C5a antigen, PLGA 72:25 0ug, PLGA 75:25 10ug, PLGA 75:25 30ug, and PLGA 50:50 30ug. Vaccines were administered either intramuscular (IM) or intranasal (IN). Mice were given booster doses of the same formulation and the same route of administration at 4 and 8 weeks. Serial serum and vaginal washings were obtained at weeks 4, 8, 11, 15, and 27 to determine antibody response. C5a specific IgG and IgA antibody responses were determined by colormetric ELISA. Mice were also challenged vaginally with GBS serotypes Ia, III, and V. After 24 hours, vaginal swabs were obtained, grown on blood agar plates, and number of GBS colonies were counted.
Of the various formulations and routes of delivery tested, both PLGA 75:25 30ug and 50:50 30ug IM and IN vaccines elicited a significant systemic IgG immune response with highest titers attained of 1:100,000. IgA immune responses were observed, but were inconsistent. For the vaginal colonization studies, mice vaccinated with PLGA 50:50 30ug and 75:25 30ug via the IM route showed no vaginal colonization with serotypes Ia and III. For GBS serotype V, less protective immunity was observed.
In the murine model, IM and IN administration of PLGA 50:50 30ug and 75:25 30ug vaccine formulations rendered a strong systemic immune response and prevented GBS colonization of the vaginal vault by serotypes Ia and III. Differences in protection to colonization by serotype V may be explained by differential C5a peptidase expression.
© 2011 Mosby, Inc. Published by Elsevier Inc. All rights reserved.