Demonstration of the preclinical correlate of protection for Staphylococcus aureus clumping factor A in a murine model of infection

Vaccine
Ingrid L ScullyAnnaliesa S Anderson

Abstract

The Staphylococcus aureus virulence factor clumping factor A (ClfA) is a component of an investigational S. aureus prophylactic vaccine. ClfA enables S. aureus to bind to fibrinogen and platelets during the initial stages of invasive disease. Here we demonstrate that ectopic expression of ClfA is sufficient to render nonpathogenic Lactococcus lactis lethal in a murine model of systemic infection. In contrast, L. lactis expressing ClfAY338A, which cannot bind fibrinogen, did not cause death in the mice. Pathogenicity was also prevented by immunization with ClfA. This model was then used to define a preclinical correlate of protection by measuring functional antibody in a S. aureus fibrinogen binding inhibition assay (FBI) and correlating that titer with protective outcomes. Although many humans have pre-existing antibodies that bind to ClfA, only sera with a threshold functional titer in the FBI were protective in this preclinical model. This confirms that fibrinogen binding is critical for ClfA-mediated pathogenesis and demonstrates that functional antibodies against ClfA are sufficient to protect against ClfA-mediated pathogenesis in vivo, enabling the definition of a preclinical correlate of protection for ClfA-containing vac...Continue Reading

References

Nov 25, 1998·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·E F BerbariD R Osmon
Jul 10, 2004·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·Glenys HarringtonMelissa Aberline
Jun 12, 2008·The Journal of Infectious Diseases·Pamela S HairKenji M Cunnion
Oct 27, 2011·PLoS Pathogens·Molly McAdowDominique M Missiakas

❮ Previous
Next ❯

Citations

Sep 2, 2016·Nature Reviews. Disease Primers·Thomas L HollandVance G Fowler
Apr 28, 2016·Expert Review of Vaccines·Gustavo H DayanAnnaliesa S Anderson
Jan 26, 2017·The British Journal of Surgery·N MohamedA S Anderson
Sep 15, 2018·Human Vaccines & Immunotherapeutics·A GurtmanA S Anderson
Aug 24, 2018·MSphere·Christopher D DupontJ Christopher Love
Mar 27, 2020·Dermatitis : Contact, Atopic, Occupational, Drug·Jonwei HwangVivian Y Shi
Apr 4, 2021·International Journal of Molecular Sciences·Anne-Marije HulshofHugo Ten Cate

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR & Staphylococcus

CRISPR-Cas system enables the editing of genes to create or correct mutations. Staphylococci are associated with life-threatening infections in hospitals, as well as the community. Here is the latest research on how CRISPR-Cas system can be used for treatment of Staphylococcal infections.