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Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses.

ABSTRACT: Staphylococcus aureus infections result in abscesses as well as septicemia. Even with therapy, abscesses can persist or even reoccur, as staphylococcal infections fail to induce protective immune responses. Here, we show that prior infection with certain attenuated strains may elicit protective immunity. A closer examination reveals that protection correlates with antibody responses elicited on exposure to particular attenuated variants. Linear regression analysis was used to compare reduction in staphylococcal disease and antibody responses to infection with wild-type and attenuated variants. This analysis identified protective antigens that, when tested as vaccines in mice, elicited disease protection. Protection afforded by attenuated strains correlates in part with the ability of Staphylococcus aureus to modulate B cell responses via protein A (spa encoded). We designate this approach "genetic vaccinology," since it exploits genetic variants to draw a correlation between disease protection and humoral immune responses for the deduction of vaccine antigens. Genetic vaccinology is particularly useful for microbes that do not elicit natural protective immunity during infection.

SUBMITTER: Kim HK

PROVIDER: S-EPMC3177580 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses.

Kim Hwan Keun HK Kim Hye-Young HY Schneewind Olaf O Missiakas Dominique D

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20110713 10

Staphylococcus aureus infections result in abscesses as well as septicemia. Even with therapy, abscesses can persist or even reoccur, as staphylococcal infections fail to induce protective immune responses. Here, we show that prior infection with certain attenuated strains may elicit protective immunity. A closer examination reveals that protection correlates with antibody responses elicited on exposure to particular attenuated variants. Linear regression analysis was used to compare reduction i ...[more]

PMID: 21753082

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Project description:IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses against Staphylococcus aureus might generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 different S. aureus virulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alpha-toxin, chemotaxis inhibitory protein of S. aureus (CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistent S. aureus carriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with high S. aureus carriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.

Dataset Information

Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses.

Publications

Identifying protective antigens of Staphylococcus aureus, a pathogen that suppresses host immune responses.

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