A promising bioconjugate vaccine against hypervirulent Klebsiella pneumoniae .

Autor:	Feldman MF; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.; VaxNewMo, St. Louis, MO 63108., Mayer Bridwell AE; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110., Scott NE; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC 3010, Australia., Vinogradov E; Human Health Therapeutics, National Research Council Canada, Ottawa, ON K1A 0R6, Canada., McKee SR; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110., Chavez SM; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110., Twentyman J; Division of Pediatric Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110., Stallings CL; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110., Rosen DA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110.; Division of Pediatric Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110., Harding CM; VaxNewMo, St. Louis, MO 63108; christian.harding@vaxnewmo.com.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Sep 10; Vol. 116 (37), pp. 18655-18663. Date of Electronic Publication: 2019 Aug 27.
DOI:	10.1073/pnas.1907833116
Abstrakt:	Hypervirulent Klebsiella pneumoniae (hv Kp ) is globally disseminating as a community-acquired pathogen causing life-threatening infections in healthy individuals. The fact that a dose as little as 50 bacteria is lethal to mice illustrates the dramatic increase of virulence associated with hv Kp strains compared with classical K. pneumoniae (c Kp ) strains, which require lethal doses greater than 10 7 bacteria. Until recently, these virulent strains were mostly antibiotic-susceptible. However, multidrug-resistant (MDR) hv Kp strains have been emerging, spawning a new generation of hypervirulent "superbugs." The mechanisms of hypervirulence are not fully defined, but overproduction of capsular polysaccharide significantly impedes host clearance, resulting in increased pathogenicity of hv Kp strains. While there are more than 80 serotypes of K. pneumoniae , the K1 and K2 serotypes cause the vast majority of hypervirulent infections. Therefore, a glycoconjugate vaccine targeting these 2 serotypes could significantly reduce hv Kp infection. Conventionally, glycoconjugate vaccines are manufactured using intricate chemical methodologies to covalently attach purified polysaccharides to carrier proteins, which is widely considered to be technically challenging. Here we report on the recombinant production and analytical characterization of bioconjugate vaccines, enzymatically produced in glycoengineered Escherichia coli cells, against the 2 predominant hypervirulent K. pneumoniae serotypes, K1 and K2. The K. pneumoniae bioconjugates are immunogenic and efficacious, protecting mice against lethal infection from 2 hv Kp strains, NTUH K-2044 and ATCC 43816. This preclinical study constitutes a key step toward preventing further global dissemination of hypervirulent MDR hv Kp strains. Competing Interests: Conflict of interest statement: M.F.F. and C.M.H. have a financial stake in VaxNewMo, a for-profit entity developing bioconjugate vaccines against Streptococcus pneumoniae and Klebsiella pneumoniae using patented technology derived from the data presented in this and other published manuscripts. (Copyright © 2019 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu