A semisynthetic glycoconjugate vaccine against resistant klebsiella pneumoniae st258

Session: 
S3.1 Vaccines
Code: 
OL3.1.3
Location (hall): 
Glucose
Start/end time: 
Monday, July 1, 2019 - 17:45 to 18:00
Marilda
Lisboa

Marilda P. Lisboa1, Jessica Przygodda1, Bopanna Monnanda1, Sharavathi G. Parameswarappa1, Sylvia Oestreich1, Arun Naini1, Daniel Knopp1, Arne Von Bonin2, Claney L. Pereira1

1Vaxxilon, Berlin, Germany, 2Vaxxilon, Reinach, Switzerland

Klebsiella pneumoniae is a frequent pathogen in antibiotic resistant nosocomial infections and a leading  cause  of serious bacterial neonatal infections in developing countries. [1],[2] K. pneumoniae is the second most common cause of Gram-negative bloodstream infections, mainly in immunocompromised patients.[3] Vaccines are important tools against antimicrobial resistance and nosocomial infections. Capsular polysaccharides and lipopolysaccharides are key vaccine targets. K. pneumoniae produces a diverse array of capsular polysaccharides or K antigens (78 types) compared to only 9 different lipopolysaccharides (O-antigen).  A 24-valent K. pneumoniae capsular polysaccharide vaccine showed safety and immunogenicity in human trials (phase 1), however the protection coverage was not over 70%.[4] Herein, we focus on the development of a semi-synthetic conjugate vaccine against the hypervirulent ST258 strain, which is present in 70% of the infections caused by carbapenem-resistant K. pneumoniae. The predominant LPS O-antigen expressed by the ST258 strain is galactan III (→3)-β-D-Galf-(1→3)-[α-D-Galp-(1→4)]-α-D-Galp-(1→). A series of oligosaccharides containing different lengths of galactan III were synthesized, conjugated to the carrier protein CRM197 and the immunogenicity tested in mice. The vaccine was shown to be immunogenic and cross-reactive against the LPS O-antigen.

References: 
  1. Zaidi AK, Huskins WC, Thaver D et al. Lancet 2005, 365, 1175.
  2. Landman D, Babu E, Shah N, Kelly P et al. J Antimicrob Chemother 2012, 67, 1427.
  3. Brady M, Cunney R, Murchan S et al. Eur J Clin Microbiol 2016, 35, 1777.
  4. Ahmad TA, El-Sayed LH, Haroun M et al. Vaccine 2012a, 30, 2411.

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