A Streptococcus suis Live Vaccine Suppresses Streptococcal Toxic Shock-Like Syndrome and Provides Sequence Type-Independent Protection

Abstract Background Streptococcus suis is an encapsulated zoonotic pathogen. Increasing antimicrobial resistance invokes the need for effective vaccines. Despite many attempts to develop an effective vaccine, none is currently available. Methods A capsular polysaccharide (CPS)-expressing attenuated...

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Published in:The Journal of infectious diseases 2019-01, Vol.219 (3), p.448-458
Main Authors: Li, Zhiwei, Chang, Peixi, Xu, Jiali, Tan, Chen, Wang, Xiaohong, Bei, Weicheng, Li, Jinquan
Format: Article
Language:English
Subjects:
Antimicrobial resistance
Capsular polysaccharides
Cell culture
Cytotoxicity
Feasibility studies
Immunization
Innate immunity
Lymphocytes T
Mutants
Pathogens
Septic shock
Streptococcus infections
Streptococcus suis
Vaccines
Virulence
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Summary:Abstract Background Streptococcus suis is an encapsulated zoonotic pathogen. Increasing antimicrobial resistance invokes the need for effective vaccines. Despite many attempts to develop an effective vaccine, none is currently available. Methods A capsular polysaccharide (CPS)-expressing attenuated mutant 2015033 was constructed by deleting 5 virulence-associated factors (sly, scpA, ssnA, fhb, and ssads) in an infective S. suis strain SC19. The safety and immune effect of 2015033 were determined both in vitro and in vivo. Results Deletion of 5 genes did not impact the growth ability and CPS generation of 2015033, and the mutant exhibited no cytotoxicity in different cell models. 2015033 was more easily eliminated by innate immunity both in vitro and in vivo. In addition, 2015033 showed a diminished invasive ability in different mouse organs (brain, lung, and liver) and avirulent properties in mice associated with weak inflammation-inducing ability. Immunization with 2015033 triggered T cell-dependent immunity, suppressed streptococcal toxic shock-like syndrome, and conferred sequence type-independent protection to mice during infection. Conclusions This study presents the feasibility of the strategy of multigene deletion for the development of promising live vaccines against invasive encapsulated pathogens. We constructed a capsular polysaccharide-expressing live vaccine against Streptococcus suis. Safety of the vaccine strain was evaluated in vitro and in vivo. Immunization with this live vaccine suppressed streptococcal toxic shock-like syndrome and conferred sequence type-independent protection.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiy512