P-1159. S. aureus α-toxin Neutralization Antibody Reduces Risk for Recurrent Skin and Soft Tissue Infection in Children
Authors: Kao Carol , Wright Jaclyn , Boyle Mary G , Forbes Andrea , Hulten Kristina G , McNeil Jonathon C , Kaplan Sheldon L , Fritz Stephanie A , Bubeck-Wardenburg Juliane 
Published: January 2025

Abstract

Background
Staphylococcus aureus is the leading bacterial cause of infectious-related mortality worldwide. To date, immune correlates of protection are undefined, resulting in unsuccessful vaccine development attempts. Anti-S. aureus α-toxin (Hla) IgG response is the only identified correlate of protection against recurrent infection in children. We aimed to correlate the anti-Hla neutralization antibody (Nab) response against risk of recurrent S. aureus infection.

Methods
We utilized serum and plasma samples from two prospective, observational studies enrolling children: 1) healthy controls with or without S. aureus colonization, 2) culture-confirmed S. aureus skin and soft tissue infection (SSTI), or 3) acute invasive S. aureus infection. Patients with risk factors for healthcare-associated S. aureus infections were excluded. Acute blood samples were drawn at enrollment/acute infection and convalescent samples 4-8 weeks later. Fold induction titer was calculated as a ratio between the convalescent and acute anti-Hla Nab titer. All participants were followed longitudinally every 3 months for 1 year to document recurrent infection. Anti-Hla IgG was determined by ELISA and anti-Hla Nab titer by RBC lysis assay.

Results
A total of 254 participants were included in the overall analyses. Children with SSTI had a 4.77 (95% CI: 2.15 to 10.19) increased odds of having a recurrent infection and were younger (mean age: 2.51 vs 5.17 years, p&lt; 0.0001) compared to those with invasive infection (Table 1). Acute and convalescent titers were compared across patients: children with invasive infections had the highest acute anti-Hla NAb titers while non-colonized controls had the lowest (1.62 vs. 0.55, p&lt; 0.0001). Children with SSTI and no recurrent infections had higher convalescent to acute anti-Hla NAb titers. Among patients with SSTI, for each unit increase in the log fold induction anti-Hla NAb titer, children with SSTI had a 0.54 (95% CI: 0.31-0.96) decreased odds of recurrent infection within 12 months of follow-up. We did not see a similar trend in the invasive group.

Conclusion
Higher anti-Hla NAb fold induction titer correlated significantly with a decreased risk of recurrent SSTI infection. Our study supports the advancement of Hla as an antigenic target for S. aureus vaccine development.

Disclosures
Kristina G. Hulten, PhD, Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Jonathon C. McNeil, MD, Nabriva: site investigator on clinical trial Sheldon L. Kaplan, MD, Pfizer: Grant/Research Support Juliane Bubeck-Wardenburg, MD, PhD, Aridis Pharmaceuticals: I have a financial agreement with Aridis Pharmaceuticals related to patents owned by the University of Chicago|Forward Defense, LLC: I may receive royalty income based on a technology developed in my laboratory that is currently owned by Washington University and subject to licens|Forward Defense, LLC: Ownership Interest