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Enhanced Staphylococcus aureus protection by uncoupling of the α-toxin-ADAM10 interaction during murine neonatal vaccination

Author

Listed:
  • Kelly L. Tomaszewski

    (Washington University School of Medicine
    LLC)

  • Meagan Blanchard

    (Washington University School of Medicine)

  • Reuben Olaniyi

    (Washington University School of Medicine
    Merck & Co)

  • Hannah R. Brenton

    (Washington University School of Medicine)

  • Samantha Hayes

    (Washington University School of Medicine
    St. Jude Children’s Research Hospital)

  • Farheen Fatma

    (Washington University School of Medicine)

  • Gaya K. Amarasinghe

    (Washington University School of Medicine)

  • Byoung-Kyu Cho

    (Mass Spectrometry Technology Access Center at the McDonnell Genome Institute - Washington University School of Medicine)

  • Young Ah Goo

    (Mass Spectrometry Technology Access Center at the McDonnell Genome Institute - Washington University School of Medicine)

  • Andrea C. DeDent

    (The University of Chicago
    Cleveland Clinic)

  • Stephanie A. Fritz

    (Washington University School of Medicine)

  • Juliane Bubeck Wardenburg

    (Washington University School of Medicine
    LLC)

Abstract

Staphylococcus aureus remains a leading global cause of bacterial infection-associated mortality and has eluded prior vaccine development efforts. S. aureus α-toxin (Hla) is an essential virulence factor in disease, impairing the T cell response to infection. The anti-Hla antibody response is a correlate of human protective immunity. Here we observe that this response is limited early in human life and design a vaccine strategy to elicit immune protection against Hla in a neonatal mice. By targeted disruption of the interaction of Hla with its receptor ADAM10, we identify a vaccine antigen (HlaH35L/R66C/E70C, HlaHRE) that elicits an ~100-fold increase in the neutralizing anti-Hla response. Immunization with HlaHRE enhances the T follicular helper (TFH) cell response to S. aureus infection, correlating with the magnitude of the neutralizing anti-toxin response and disease protection. Furthermore, maternal HlaHRE immunization confers protection to offspring. Together, these findings illuminate a path for S. aureus vaccine development at the maternal-infant interface.

Suggested Citation

  • Kelly L. Tomaszewski & Meagan Blanchard & Reuben Olaniyi & Hannah R. Brenton & Samantha Hayes & Farheen Fatma & Gaya K. Amarasinghe & Byoung-Kyu Cho & Young Ah Goo & Andrea C. DeDent & Stephanie A. Fr, 2024. "Enhanced Staphylococcus aureus protection by uncoupling of the α-toxin-ADAM10 interaction during murine neonatal vaccination," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52714-7
    DOI: 10.1038/s41467-024-52714-7
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    References listed on IDEAS

    as
    1. Fangming Zhu & Ryan J. McMonigle & Andrew R. Schroeder & Xianyou Xia & David Figge & Braxton D. Greer & Edahí González-Avalos & Diego O. Sialer & Yin-Hu Wang & Kelly M. Chandler & Adam J. Getzler & Em, 2023. "Spatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4+ T cell fate," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
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