Development and Immunogenicity of a Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine

Jeremy A. Duke, Amy V. Paschall, Lloyd S. Robinson, Cory J. Knoot, Evgeny Vinogradov, Nichollas E. Scott, Mario F. Feldman, Fikri Y. Avci, Christian M. Harding

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Group B Streptococcus (GBS) is a leading cause of neonatal infections and invasive diseases in nonpregnant adults worldwide. Developing a protective conjugate vaccine targeting the capsule of GBS has been pursued for more than 30 years; however, it has yet to yield a licensed product. In this study, we present a novel bioconjugation platform for producing a prototype multivalent GBS conjugate vaccine and its subsequent analytical and immunological characterizations. Using a glycoengineering strategy, we generated strains of Escherichia coli that recombinantly express the type Ia, type Ib, and type III GBS capsular polysaccharides. We then combined the type Ia-, Ib-, and III-capsule-expressing E. coli strains with an engineered Pseudomonas aeruginosa exotoxin A (EPA) carrier protein and the PglS oligosaccharyltransferase. Coexpression of a GBS capsule, the engineered EPA protein, and PglS enabled the covalent attachment of the target GBS capsule to an engineered serine residue on EPA, all within the periplasm of E. coli. GBS bioconjugates were purified, analytically characterized, and evaluated for immunogenicity and functional antibody responses. This proof-of-concept study signifies the first step in the development of a next-generation multivalent GBS bioconjugate vaccine, which was validated by the production of conjugates that are able to elicit functional antibodies directed against the GBS capsule.

Original languageEnglish
Pages (from-to)3111-3123
Number of pages13
JournalACS Infectious Diseases
Volume7
Issue number11
DOIs
StatePublished - Nov 12 2021

Keywords

  • bioconjugate
  • bioconjugation
  • capsule
  • conjugate vaccine
  • group B Streptococcus
  • multivalent

Fingerprint

Dive into the research topics of 'Development and Immunogenicity of a Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine'. Together they form a unique fingerprint.

Cite this