Commercial Intravenous Immunoglobulin (IVIg) Preparations Contain Functional Neutralizing Antibodies Against the Staphylococcus aureus Leukocidin LukAB (LukGH) [PublishAheadOfPrint]

The pathogenesis of Staphylococcus aureus is mediated by an array of important virulence factors, including the two-component leukocidin family of toxins. LukAB (also known as LukGH), the most recently discovered leukocidin, is potently lethal to phagocytes, produced during invasive human disease, and present in all known clinical isolates of S. aureus. Intravenous immunoglobulin (IVIg) is often used clinically in severe S. aureus infections. The primary aim of this study was to assess the binding and neutralization potential of IVIg against LukAB. A secondary aim was to examine the lot-to-lot variability of IVIg in the binding and neutralization of LukAB. We studied twenty-four distinct lots of IVIg and compared them to serum from children with invasive S. aureus infection (in the acute and convalescent phases) and healthy, uninfected controls. We found that all lots of IVIg contained functional antibodies targeting LukAB. After adjusting for total antibody content per sample, we found that the amount of anti-LukAB antibody in IVIg was similar to healthy controls and less than patients with invasive S. aureus infection. IVIg samples had relatively lower neutralization capacity compared to healthy controls and children with invasive infection. IVIg had remarkably little lot-to-lot variation in LukAB binding, but had significantly more variation in toxin neutralization. These results are the first report of functional antibodies against the important S. aureus leukocidin LukAB in IVIg. Given the frequent clinical use of IVIg for severe S. aureus infections, improving our understanding of functional antibody properties exhibited by this therapeutic is essential.

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