Abstract
Background: Although the relevance of humoral immunity for protection against S. aureus skin and soft tissue infections (SSTIs) has been suggested by several animal and human studies, the question of which human antibodies may be protective has so far impeded the development of a safe and effective vaccine. Because most adults have developed certain anti-S. aureus antibodies due to S. aureus colonization or infection, we hypothesized that the titers of antibodies to S. aureus in uninfected controls would differ from those in infected patients and would also differ in infected patients from the time of acute infection to a 40-day convalescent serum.Methods: To test these hypotheses, we measured human antibody levels against a panel of 134 unique antigens comprising the S. aureus surfome and secretome in subjects with active culture-confirmed S. aureus SSTIs (cases) and in controls with no infection, using a novel S. aureus protein microarray.Results: Most S. aureus SSTI patients (n = 60) and controls (n = 142) had antibodies to many of the tested S. aureus antigens. Univariate analysis showed statistically weak differences in the IgG levels to some antigens in the SSTI patient (case) sera compared with controls. Antibody levels to most tested antigens did not increase comparing acute with 40-day serum. Multiple logistic regression identified a rich subset of antigens that, by their antibody levels, together correctly differentiated all cases from all controls.Conclusions: Antibodies directed against S. aureus antigens were present both in patients with S. aureus SSTIs and in uninfected control patients. We found that SSTI patients and controls could be distinguished only based on differences in antibody levels to many staphylococcal surface and secreted antigens. Our results demonstrate that in the studied population, the levels of anti-S. aureus antibodies appear largely fixed, suggesting that there may be some level of unresponsiveness to natural infection.
Highlights
Staphylococcus aureus is a common cause of human infections, of skin and soft tissue infections (SSTIs) [1]
Blood samples were obtained from cases at enrollment and after 40 days, hereafter referred to as day 0 (D0) and day 40 (D40), and from controls at the single time point when they presented for care
Antibody responses against all 134 S. aureus surface or secreted antigens were generated for a total of 60 SSTI subject blood samples collected both at D0 and at D40 and for 142 controls, for a case:control ratio of ∼1:2 and total sample size of 202 subjects
Summary
Staphylococcus aureus is a common cause of human infections, of skin and soft tissue infections (SSTIs) [1]. Some groups have detected anti-S. aureus antibodies in healthy controls without a history of recent or current SSTI [17,18,19,20], suggesting that colonization alone may result in the development of a broad repertoire of anti-staphylococcal antibodies. It is not clear whether the specificity and titers of these antibodies can be distinguished from the antibodies generated during or immediately following an acute S. aureus skin infection. IgG levels above the background level were detectable against most antigens
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