Prime-boost vaccination combining rF1-V subunit and novel live attenuated bacterial strains protects mice from virulent aerosolized nonencapsulated Yersinia pestis
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B931
Abstract ID: 5070
Presenting Author:
Michael L Davies
Abstract:
Yersinia pestis (Yp) is a security concern since it can be aerosolized and cause pneumonic plague, a rapidly progressing illness that is fatal if not treated promptly with antibiotics. There are no FDA-approved vaccines, and candidate vaccines are less effective against pneumonic than bubonic plague. The major protective vaccine antigen has been the F1 capsule protein; protection against nonencapsulated strains has been elusive. We constructed two novel live attenuated vaccine (LAV) strains on the pgm-pPst- background, which is excluded from the CDC select agent list due to established safety. These strains, Δcaf1 and ΔyopD/Δcaf1, lack F1 and may be more effective at inducing immunity against nonencapsulated strains like C12. Female BALB/c mice were immunized with a heterologous prime-boost strategy combining one subcutaneous injection of novel LAV and one of recombinant F1-V (rF1-V) subunit, then challenged with aerosolized virulent Yp C12 and monitored for survival, bacterial load, and immunological factors. Priming with rF1-V and boosting with LAV was more protective than the reverse strategy. Protection was accompanied by high antibody titers against rF1-V and rV. rF1-V prime and LAV boost also led to a higher IgG2a/IgG1 antibody ratio than the reverse, suggesting a balanced Th1/Th2 response. These data support rF1-V prime and pgm-pPst-Δcaf1 LAV boost as a promising strategy for a safe and effective vaccine against both encapsulated and nonencapsulated Yp.
Prime-boost vaccination combining rF1-V subunit and novel live attenuated bacterial strains protects mice from virulent aerosolized nonencapsulated Yersinia pestis
Category
Poster