Evidence for Staphylococcus aureus α-toxin as a Dominant Antigen in Severe Pediatric Influenza-staphylococcal Co-infection — Implications for Therapy
Methods: Quantitative in vitro assays measuring anti-Hla IgG and Hla-neutralizing activity were developed. In collaboration with the Pediatric Acute Lung Injury and Sepsis Investigators, sera from 57 severely-ill influenza patients admitted to pediatric intensive care units were prospectively collected and analyzed. Serial specimens were available for 34 children.
Results: Day 0 sera (indicating pre- or early disease exposure) displayed anti-Hla activity that spanned 1–2 orders of magnitude, with no difference in serologic activity in patients mono-infected with influenza versus those co-infected with either methicillin-sensitive (MS-) or MRSA. However, Hla-antibody significantly increased in those with MRSA co-infection (median 16-fold increase from baseline, p < 0.001 v. MSSA or influenza only). In some children, anti-Hla IgG and neutralization activity increased over 100-fold in 2 weeks.
Conclusion: Hla is a potent immunogen in influenza-S. aureus co-infection, consistent with toxin production early in disease. The observation of elevated anti-toxin titers in influenza-MRSA co-infected children suggests that toxin-mediated lung injury may exacerbate disease in this population, highlighting potential benefit from Hla-neutralization therapy in early influenza infection. These data provide impetus for ongoing studies to understand pathogen synergy, the role of Hla, and targeted disease interventions.
Project support is from the Depts. of Microbiology and Pediatrics (University of Chicago), the NIH (AI084011) and the CDC.
J. Bubeck Wardenburg, Novartis Vaccines and Diagnostics: (see comment), JBW has the potential to receive royalties from Novartis Vaccines and Diagnostics in relation to patents owned by the University of Chicago.