Global antibody response to Staphylococcus aureus live-cell vaccination.

The pathogen Staphylococcus aureus causes a broad range of severe diseases and is feared for its ability to rapidly develop resistance to antibiotic substances. The increasing number of highly resistant S. aureus infections has accelerated the search for alternative treatment options to close the widening gap in anti-S. aureus therapy. This study analyses the humoral immune response to vaccination of Balb/c mice with sublethal doses of live S. aureus. The elicited antibody pattern in the sera of intravenously and intramuscularly vaccinated mice was determined using of a recently developed protein array. We observed a specific antibody response against a broad set of S. aureus antigens which was stronger following i.v. than i.m. vaccination. Intravenous but not intramuscular vaccination protected mice against an intramuscular challenge infection with a high bacterial dose. Vaccine protection was correlated with the strength of the anti-S. aureus antibody response. This study identified novel vaccine candidates by using protein microarrays as an effective tool and showed that successful vaccination against S. aureus relies on the optimal route of administration.

Specific serum IgG at diagnosis of Staphylococcus aureus bloodstream invasion is correlated with disease progression.

UNLABELLED: Although Staphylococcus aureus is a prominent cause of infections, no vaccine is currently available. Active vaccination relies on immune memory, a core competence of the adaptive immune system. To elucidate whether adaptive immunity can provide protection from serious complications of S. aureus infection, a prospective observational study of 44 patients with S. aureus infection complicated by bacteremia was conducted. At diagnosis, serum IgG binding to S. aureus extracellular proteins was quantified on immunoblots and with Luminex-based FLEXMAP 3D™ assays comprising 64 recombinant S. aureus proteins. Results were correlated with the course of the infection with sepsis as the main outcome variable. S. aureus-specific serum IgG levels at diagnosis of S. aureus infection were lower in patients developing sepsis than in patients without sepsis (P<0.05). The pattern of IgG binding to eight selected S. aureus proteins correctly predicted the disease course in 75% of patients. Robust immune memory of S. aureus was associated with protection from serious complications of bacterial invasion. Serum IgG binding to eight conserved S. aureus proteins enabled stratification of patients with high and low risk of sepsis early in the course of S. aureus infections complicated by bacteremia. SIGNIFICANCE: S. aureus is a dangerous pathogen of ever increasing importance both in hospitals and in the community. Due to the crisis of antibiotic resistance, an urgent need exists for new strategies to combat S. aureus infections, such as vaccination. To date, however, all vaccine trials have failed in clinical studies. It is therefore unclear whether the adaptive immune system is at all able to control S. aureus in humans. The paper demonstrates the use of proteomics for providing an answer to this crucial question. It describes novel results of a prospective study in patients with S. aureus infection complicated by bloodstream invasion. Immune proteomic analysis shows that robust immune memory of S. aureus - reflected by strong serum IgG antibody binding to S. aureus antigens - is associated with clinical protection from sepsis. This lends support to the notion of a vaccine to protect against the most serious complications of S. aureus infection. Hence, the data encourage further efforts in vaccine development.

Microarray-based identification of human antibodies against Staphylococcus aureus antigens.

PURPOSE: The mortality rate of patients with Staphylococcus aureus infections is alarming and urgently demands new strategies to attenuate the course of these infections or to detect them at earlier stages. EXPERIMENTAL DESIGN: To study the adaptive immune response to S. aureus antigens in healthy human volunteers, a protein microarray containing 44 S. aureus proteins was developed using the ArrayStrip platform technology. RESULTS: Testing plasma samples from 15 S. aureus carriers and 15 noncarriers 21 immunogenic S. aureus antigens have been identified. Seven antigens were recognized by antibodies present in at least 60% of the samples, representing the core S. aureus immunome of healthy individuals. S. aureus-specific serum immunoglobulin G (IgG) levels were significantly lower in noncarriers than in carriers specifically anti-IsaA, anti-SACOL0479, and anti-SACOL0480 IgGs were found at lower frequencies and quantities. Twenty-two antigens present on the microarray were encoded by all S. aureus carrier isolates. Nevertheless, the immune system of the carriers was responsive to only eight of them and with different intensities. CONCLUSION AND CLINICAL RELEVANCE: The established protein microarray allows a broad profiling of the S. aureus-specific antibody response and can be used to identify S. aureus antigens that might serve as vaccines or diagnostic markers.