Construction and screening of attenuated ΔphoP/Q Salmonella typhimurium vectored plague vaccine candidates

Human Vaccines & Immunotherapeutics
Donata R SizemoreK P Killeen

Abstract

Preclinical studies evaluating plague vaccine candidates have demonstrated that the F1 and V protein antigens of Yersinia pestis confer protection against challenge from virulent strains. Live-attenuated ΔphoP/Q Salmonella typhimurium recombinants were constructed expressing either F1, V antigens, F1 and V antigens, or a F1-V fusion from Asd (+) balanced-lethal plasmids. To improve antigen delivery, genes encoding plague antigens were modified in order to localize antigens to specific bacterial cellular compartments which include cytoplasmic, outer membrane, or secreted. Candidate vaccine strains were evaluated for growth characteristics, full-length lipopolysaccharide (LPS), plasmid stability, and antigen expression in vitro. Plague vaccine candidate strains with favorable in vitro profiles were evaluated in murine or rabbit preclinical oral immunogenicity studies. Attenuated S. typhimurium strains expressing cytoplasmically localized F1-V and V antigen antigens were more immunogenic than strains that secreted or localized plague antigens to the outer membrane. In particular, S. typhimurium M020 and M023, which express Asd(+)-plasmid derived soluble F1-V and soluble V antigen, respectively, at high levels in the bacterial cell...Continue Reading

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Citations

Aug 10, 2012·Expert Review of Vaccines·Jason A Rosenzweig, Ashok K Chopra
Jun 12, 2013·Expert Review of Vaccines·Xiaoyi WangRuifu Yang
Sep 24, 2013·Expert Review of Vaccines·Kenneth L Roland, Karen E Brenneman
Dec 18, 2013·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Onur SerefStephen S Fong
Dec 20, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Josephine E Clark-Curtiss, Roy Curtiss

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