Enhanced Staphylococcus aureus protection by uncoupling of the α-toxin-ADAM10 interaction during murine neonatal vaccination.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39379345.
- Also identified by DOI 10.1038/s41467-024-52714-7 and PMC identifier 11461939.
- Licence recorded as CC BY-NC-ND.
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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 (Hla<sub>H35L/R66C/E70C</sub>, Hla<sub>HRE</sub>) that elicits an ~100-fold increase in the neutralizing anti-Hla response. Immunization with Hla<sub>HRE</sub> enhances the T follicular helper (T<sub>FH</sub>) cell response to S. aureus infection, correlating with the magnitude of the neutralizing anti-toxin response and disease protection. Furthermore, maternal Hla<sub>HRE</sub> immunization confers protection to offspring. Together, these findings illuminate a path for S. aureus vaccine development at the maternal-infant interface.
Medical subject headings
- Staphylococcus aureus
- ADAM10 Protein
- Hemolysin Proteins
- Staphylococcal Infections
- Bacterial Toxins
- Animals, Newborn
- Staphylococcal Vaccines
- Vaccination