Protective efficacy of novel live-attenuated and subunit vaccines against pneumonic plague: comparative analyses of humoral and cellular immune responses in wild-type and IL-17 knockdown mice
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B927
Abstract ID: 4349
Presenting Author:
Emily K Hendrix , PhD Candidate at Univ. of Texas Med. Br., Galveston
Abstract:
Resistance of plague-causing Yersinia pestis to antibiotics and no FDA-approved plague vaccine highlight the importance of our study. Two live-attenuated triple mutants of Y. pestis, LMA and LMP, were generated and were avirulent in a pneumonic mouse model while retaining immunogenicity. A trivalent subunit adenoviral vector-based Ad5-YFV vaccine was also developed, effective in mice and non-human primates. We performed detailed immunological studies on LMA and LMP as well as a prime-boost strategy using combinations of Ad5-YFV with LMA or LMP to assess protective efficacy. Groups included IL-17 knockdown (KD) mice, to discern its role in protection. All vaccinated mice generated a significant humoral immune response based on IgG and its isotypes to F1-V antigen compared to unvaccinated controls. These animals were protected from disease when challenged with a virulent Y. pestis CO92. Enhanced T cell activation as well as memory and germinal center B cell responses were noted in vaccinated mice receiving LMA or LMP. Combination of vaccines increased percentages of T cells positive for IFNγ, IL-2, -4, and TNFα. While T cells positive for IL-17 were increased by vaccination of wild-type mice, the corresponding percentage was undetectable in IL-17 KD mice. Overall, LMA or LMP as well as a prime-boost vaccination with Ad5-YFV provided complete protection, with similar humoral immune responses but variable and distinct cellular immune responses in wild-type versus IL-17 KD mice.
Protective efficacy of novel live-attenuated and subunit vaccines against pneumonic plague: comparative analyses of humoral and cellular immune responses in wild-type and IL-17 knockdown mice
Category
Poster and Podium (Block Symposium)