Park, and P

Park, and P. administered alone or with cholera toxin, whereas a high degree of GAS colonization of NALT was observed in control mice immunized with phosphate-buffered saline only. Moreover, administration of anti-SCPA serum by the intranasal route guarded mice against streptococcal contamination. These results suggest that intranasal immunization with SCPA would prevent colonization and contamination of human tonsils, thereby eliminating potential reservoirs that maintain endemic disease. The only known reservoir for group A streptococcus (GAS) is usually humans, where more than 150 M genotypes have evolved the potential to cause diseases ranging from relatively mild skin disease to infections with high mortality such as necrotizing fasciitis. This very common pathogen is the cause for millions of prescriptions of antibiotics the world over and the single most important cause of heart valve disease in most resource-poor countries (5, 17). A common scenario is the following. A child aged 4 to 12 years is usually GS-9620 treated with one of several antibiotics, and treatment brings relief GS-9620 from symptoms of GAS pharyngitis. Nearly one-third of such children, however, continue to shed streptococci, and a significant number develop recurrent disease caused by the same strain (15, 22, 29, 33). This cycle may be repeated several times during the strep throat season in temperate climates. Considerable evidence points to tonsils as the primary reservoir for recurrent infections, a reservoir that maintains this bacterial pathogen in human populations (15, 29). Early efforts to use M protein purified from streptococci in vaccines were curtailed following a small study in which vaccination was associated Akt1 with a considerable increase in acute rheumatic fever (14, 27). However, the global rise in severe streptococcal infections, such as toxic shock and necrotizing fasciitis, in the 1990s prompted both commercial and public health interests to restart development of vaccines for prevention of GAS infections and their complications. The antiphagocytic M protein is now the target of vaccine development by three research groups (11, 13, 16). The conserved P145 peptide epitope within the C repeats and proximal to the cell wall is the focus of Good et al. (16). Fischetti and colleagues have centered their efforts on the entire C repeat region, which they express on the surface of (6, 9). Cross-species protection was expected, because the two proteins are 98% identical in GS-9620 amino acid sequence (8). Epidemiological data suggest that GAS has a strong tropism for human tonsils (29), a tropism that we confirmed in an intranasal murine model of contamination (30). Nasal mucosa-associated lymphoid tissue (NALT) is the main streptococcal target following intranasal inoculation of mice (30). Because persistence of GS-9620 GAS in tonsils following antibiotic therapy is usually thought to be the primary source of this pathogen, the optimal vaccine should prevent or eliminate colonization of that tissue. This in turn should reduce the reservoir and provide for maximum herd immunity in the overall population. To test this possibility, experiments were designed to evaluate whether intranasal inoculation of SCPAw either alone or with cholera toxin (CTX), a known mucosal adjuvant, can prevent contamination and colonization of NALT. Experiments were performed using a bioluminescent M49 strain, Xen-20, which was generated by introducing a altered cassette into the chromosome (30); thus, persistence of streptococci in NALT could be monitored by optical biophotonic imaging from your noses of live mice or by viable counts of streptococci in dissected NALT. Experiments showed that intranasal immunization.