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

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 corr...

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Vydáno v:	Nature communications Ročník 15; číslo 1; s. 8702 - 14
Hlavní autoři:	Tomaszewski, Kelly L., Blanchard, Meagan, Olaniyi, Reuben, Brenton, Hannah R., Hayes, Samantha, Fatma, Farheen, Amarasinghe, Gaya K., Cho, Byoung-Kyu, Goo, Young Ah, DeDent, Andrea C., Fritz, Stephanie A., Wardenburg, Juliane Bubeck
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 08.10.2024 Nature Publishing Group Nature Portfolio
Témata:	13/31 14 38 59 631/250/255/1318 631/326/41/2533 631/326/590/2294 64 64/60 692/308/575 82/58 ADAM10 Protein - immunology ADAM10 Protein - metabolism Amyloid Precursor Protein Secretases - immunology Amyloid Precursor Protein Secretases - metabolism Animal models Animals Animals, Newborn Antibodies, Bacterial - immunology Antibodies, Neutralizing - immunology Antibody response Antitoxins Bacterial diseases Bacterial Toxins - immunology Bacterial Toxins - metabolism Female Hemolysin Proteins - immunology Hemolysin Proteins - metabolism Histocompatibility antigen HLA Humanities and Social Sciences Humans Immunity Immunization Lymphocytes Lymphocytes T Membrane Proteins - immunology Membrane Proteins - metabolism Mice Mice, Inbred C57BL multidisciplinary Neonates Neutralizing Offspring Science Science (multidisciplinary) Staphylococcal Infections - immunology Staphylococcal Infections - prevention & control Staphylococcal Vaccines - administration & dosage Staphylococcal Vaccines - immunology Staphylococcus aureus Staphylococcus aureus - immunology Staphylococcus infections Toxins Vaccination Vaccine development Vaccines Virulence factors α-Toxin
ISSN:	2041-1723, 2041-1723
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Shrnutí:	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 (Hla H 35L/ R 66C/ E 70C , Hla HRE ) that elicits an ~100-fold increase in the neutralizing anti-Hla response. Immunization with Hla HRE enhances the T follicular helper (T FH ) cell response to S. aureus infection, correlating with the magnitude of the neutralizing anti-toxin response and disease protection. Furthermore, maternal Hla HRE immunization confers protection to offspring. Together, these findings illuminate a path for S. aureus vaccine development at the maternal-infant interface. Staphylococcus aureus infection results in robust induction of immunity but the development of efficacious vaccines remains challenging. Here the authors present a vaccine that amplifies T cell immunity early in life by targeting the S. aureus α-toxin-ADAM10 interaction in a murine model.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-52714-7