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- W2006382274 abstract "ABSTRACT Staphylococcus aureus infection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links V H 3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High V H 3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpA KKAA , which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity. IMPORTANCE Staphylococcus aureus is the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines." @default.
- W2006382274 created "2016-06-24" @default.
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- W2006382274 date "2015-02-27" @default.
- W2006382274 modified "2023-09-27" @default.
- W2006382274 title "Protein A Suppresses Immune Responses during Staphylococcus aureus Bloodstream Infection in Guinea Pigs" @default.
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- W2006382274 doi "https://doi.org/10.1128/mbio.02369-14" @default.
- W2006382274 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4313907" @default.
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