Editors' ChoiceInfectious Disease

Fighting staph: Not child’s play

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Science Translational Medicine  17 Jan 2018:
Vol. 10, Issue 424, eaar7518
DOI: 10.1126/scitranslmed.aar7518

Abstract

Neutralizing antibodies to Staphylococcus aureus alpha-toxin are acquired in adolescence and augmented by infection or colonization.

Staphylococcus aureus is the leading cause of skin and soft tissue infections, endocarditis, and osteomyelitis in the developed world. With increasing prevalence of methicillin-resistant strains and the imminent threat of additional resistance mechanisms, there is an urgent need for new therapies to combat this frequent pathogen. Because attempts to develop a protective vaccine have thus far proven unsuccessful, alternative immune-based therapeutic strategies are being examined and may be informed by a recent report that sheds new light on the humoral immune response to this bacterium.

Alpha-toxin is a cytolytic, highly conserved S. aureus virulence factor and the target of a monoclonal antibody currently in clinical trials to combat S. aureus infection. Wu et al. comprehensively quantified serum levels of both total alpha-toxin-reactive immunoglobulin G (IgG) and neutralizing antibodies (nAb) protective against alpha-toxin–induced hemolysis in over 300 healthy subjects of various ages. Although IgG and nAbs were found in all subjects, infants less than one year of age had the lowest titers, perhaps reflecting maternally transferred IgG. Children 2 to 10 years old had total IgG approaching adult levels, but “mature” nAb were not seen until adolescence. Both total IgG and nAb were largely preserved in elderly adults up to 75 years old, indicating that once established, this humoral response does not degrade substantially with age. Consistent with a model in which acute S. aureus exposure boosts the host antibody response, alpha-toxin nAbs were modestly elevated in healthy subjects asymptomatically colonized with S. aureus and to a slightly greater degree in dialysis and surgical patients with S. aureus bacteremia.

These results, which build on prior studies demonstrating an association between S. aureus infection or colonization and antistaphylococcal IgG titers, provide new information about the time course for appearance and persistence of these antibodies, and identify preadolescent children as a population in whom alpha-toxin nAbs are underdeveloped. Whether this is intrinsically tied to status of the developing immune system or a function of age-dependent exposure remains unanswered. Unfortunately, though they may mitigate disease severity, antibodies alone have to date proven insufficient to prevent S. aureus infection. Thus, similarly comprehensive examinations of how age and clinical exposures influence antistaphyloccocal T cell responses in humans are needed.

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