Monomeric Crystal Structure of the Vaccine Carrier Protein CRM197 and Implications for Vaccine Development

Published

March 30, 2023

Author(s)

Andrew Lees, Natalia Oganesyan, David Travis Gallagher

Abstract

CRM197 is a genetically detoxified mutant of diphtheria toxin (DT) that is widely used as a carrier protein for conjugate vaccines. Protective immune responses to H. influenzae b, S. pneumoniae, S. Typhi and meningococcal diseases are obtained by coupling CRM to glycans and other components from those pathogens. Wild type DT has been described in two oligomeric forms, a monomer and a domain-swapped dimer. However, all available crystal structures of CRM197 have until now been dimeric, despite 30 years of research and increasing applications of CRM197 in conjugate vaccines. Here we report the crystal structure of a monomeric CRM197, expressed in E. coli. The structure enables detailed comparisons across expression system and oligomeric state, leading to a model for the monomer-dimer transition mechanism and implications for vaccine development.

Citation

Acta Crystallographica Section F - Structural Biology Communications

Volume

79

Issue

4

Pub Type

Journals

Download Paper

https://doi.org/10.1107/S2053230X23002364

Local Download

Keywords

carrier, conjugate vaccine, diphtheria toxin, domain swapping, CRM197, toxoid

Citation

Lees, A. , Oganesyan, N. and Gallagher, D. (2023), Monomeric Crystal Structure of the Vaccine Carrier Protein CRM197 and Implications for Vaccine Development, Acta Crystallographica Section F - Structural Biology Communications, [online], https://doi.org/10.1107/S2053230X23002364, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=934714 (Accessed July 23, 2025)