Development of Non-Pathogenic Staphylococci as Vaccine Delivery Vehicles
Among the bacteria being considered as live recombinant vaccine vehicles, the most well studied during the past decade are attenuated Salmonella species1 and mycobacterial bacille Calmette-Guerin (BCG) due to their capacity to colonize mucosal surfaces an
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Development of Non-Pathogenic Staphylococci as Vaccine Delivery Vehicles Stefan Stahl, Patrik Samuelson, Marianne Hansson, Christine Andreoni, Liliane Goetsch, Christine Libon, Sissela Liljeqvist, Elin Gunneriusson, Hans Binz, Thien Ngoc Nguyen and Mathias Uhlen 1.
Introduction
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mong the bacteria being considered as live recombinant vaccine vehicles, the most weH studied during the past decade are attenuated Salmonella species' and mycobacterial bacille Calmette-Guerin (BCG) due to their capacity to colonize mucosal surfaces and invade macrophages in the liver, spleen and lymph no des of the hOSt. 2 •3 Surface-display of the foreign antigens to be delivered,has in both these systems proven to be beneficial in eliciting an immune response.4-7 The risk of reversion to avirulent phenotype and the potential side-effects in immunocompromised individuals and infants have, however, raised concern of the use of Salmonella or BCG-based recombinant vaccines in humans. 8 Gram-positive bacteria have only recently been considered as vaccine delivery systems,9"° and research has focused on the use of commensal or non-pathogenic bacteria." The surface display of foreign proteins has been investigated for various Grampositive bacteria, such as staphylococci,1O streptococci9•12 and enterococci.'3 In fact, the surface displayofheterologous proteins on Gram-Positive Bacteria as Vaccine Vehicles for Mucosal Immunization, edited by G. Pozzi and I.M. Wells. © 1997 Landes Bioscience.
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Gram-Positive Bacteria for Mucosal Immunization
Gram-positive bacteria was achieved several years before Schneewind and coworkers fully elucidated the mechanisms for cell surface targeting and subsequent anchoring of receptors on staphylococcal ceIls.'4- '7 They investigated how Staphylococcus aureus protein A (SpA) was sorted to the cell surface, and suggested a highly plausible mechanism for this process. The C-terminal surface anchoring region of SpA consists of a charged repetitive region, postulated to interact with the peptidoglycan ceH wall,'8 foHowed by a region common to numerous Gram-positive cell surface proteins, whieh contains an LPXTG motif, a hydrophobie region and a short charged tail." It has been demonstrated that the latter tripartite region is required for ceH surface anchoring and that the ceH waH sorting is accompanied by proteolytie deavage within the LPXTG motif, between the threonine and glyeine residues, and subsequent covalent linking of the surface receptor to the ceH waH.'4- '7 Since the C-termini of numerous Grampositive bacterial surface receptors are highly homologous,"" 5 it is likely that there is a common mechanism for ceH surface targeting among Gram-positive bacteria. Here we describe the development of non-pathogenie staphylococei as novellive bacterial vectors for delivery of subunit vaceines. Both strains investigated, Staphylococcus xylosus and Staphylococcus carnosus, have been widely used in meat fermentation processes, e.g., as starter cultures in the ripening process of dry sausages,'9,20 and the use
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