Heterogeneous in vivo expression of clumping factor A and capsular polysaccharide by Staphylococcus aureus: Implications for vaccine design
ABSTRACT There is a clear unmet medical need for a vaccine that would prevent infections from Staphylococcus aureus (S. aureus). To validate antigens as potential vaccine targets it has to be demonstrated that the antigens are expressed in vivo. Using murine bacteremia and wound infection models, we demonstrate that the expression of clumping factor A (ClfA) and capsular polysaccharide antigens are heterogeneous and dependent on the challenge strains examined and the in vivo microenvironment. We also demonstrate opsonophagocitic activity mediated by either antigen is not impeded by the presence of the other antigen. The data presented in this report support a multiantigen approach for the development of a prophylactic S. aureus vaccine to ensure broad coverage against this versatile pathogen.
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- "All S. aureus strains possess the genetic pathway for synthesis of either CP5 or CP8 . Analysis of CP expression shows that although some strains do not express CP under in vitro growth conditions, CP expression is detected in vivo  . ClfA is a well-conserved surface antigen that facilitates S. aureus infection by binding to fibrinogen, complement proteins, and platelets, thus mediating adhesion to host tissues . "
ABSTRACT: Staphylococcus aureus is a common cause of healthcare-acquired morbidity and mortality and increased healthcare resource utilization. A prophylactic vaccine is being developed that may reduce this disease burden. Volunteers in good general health aged 50-85 (n=312) and 18-24 (n=96) years were randomized to receive a single intramuscular dose of one of three dose levels of a non-adjuvanted, 3-antigen S. aureus vaccine (SA3Ag) or placebo. SA3Ag antigens included capsular polysaccharides 5 and 8 (CP5 and CP8), each conjugated to cross-reactive material 197 (CRM197), and recombinant clumping factor A (ClfA). Safety, tolerability, and immunogenicity were evaluated. At day 29 post-vaccination, robust immune responses were observed in both age cohorts at all three SA3Ag dose levels. In the primary analysis population, the 50- to 85-year age stratum, geometric mean-fold-rises in competitive Luminex(®) immunoassay antibody titers from baseline ranged from 29.2 to 83.7 (CP5), 14.1 to 31.0 (CP8), and 37.1 to 42.9 (ClfA), all (P<0.001) exceeding the pre-defined two-fold rise criteria. Similar rises in opsonophagocytic activity assay titers demonstrated functionality of the immune response. Most injection-site reactions were mild in severity and there were no substantial differences (SA3Ag vs. placebo) with regard to systemic or adverse events. In this study of healthy adults aged 50-85 and 18-24 years, SA3Ag elicited a rapid and robust immune response and was well tolerated, with no notable safety concerns. Copyright © 2015. Published by Elsevier Ltd.Vaccine 02/2015; 4(15). DOI:10.1016/j.vaccine.2015.02.024 · 3.49 Impact Factor
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ABSTRACT: Staphylococcus aureus is the most prevalent mastitis pathogen in Argentina and worldwide. Lack of effectiveness of traditional control measures based on milking hygiene and antibiotic therapy against this organism has led to the development of alternatives directed to prevent the disease. Among them, the manipulation of host immune mechanisms through vaccination has been explored. The identification of virulence factors able to stimulate host immune defenses is key to developing a rational vaccine. S. aureus has multiple virulence factors that interact with the host at different stages of an intramammary infection. The use of some of these factors as immunogens has been shown to elicit protective responses in the host. The structure, function, and use as immunogens of S. aureus virulence factors considered to be relevant at different stages of intrammamary infections caused by this organism are reviewed in this article.Revista Argentina de microbiología 45(2):119-30. · 0.66 Impact Factor