Protective and autoimmune epitopes of streptococcal M proteins

Beachey, Edwin H.; Bronze, Michael S.; Dale, James B.; Kraus, Werner; Poirier, T.; Sargent, Susie J.

doi:10.1016/s0264-410x(88)80027-6

Cited by 44 publications

(27 citation statements)

References 21 publications

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“…Antibody responses toward GAS M protein have been extensively studied in both humans and various animal models (1,3,4,10,29), and identification of cardiac myosin (10,22) as an important autoantigen has indicated a role for autoimmunity in the pathogenesis of RHD (6,8). Opsonophagocytosis, mediated by serum opsonins, such as antibodies or complement, is a key mechanism for host protective immunity against streptococcal infection.…”

Section: Discussionmentioning

confidence: 99%

B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis

et al. 2009

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Section: Discussionmentioning

confidence: 99%

B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis

et al. 2009

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“…Lymphocytes (5 ϫ 10 6 /ml) were stimulated with various concentrations of hexavalent protein (1 to 30 g/ml) or concanavalin A (0.25 g/ml) (Sigma) in 96-well tissue culture plates (Corning Inc., Corning, N.Y.) for 72 h at 37°C with 5% CO 2 and humidity. Cells were tested in triplicate for each antigen concentration.…”

Section: Methodsmentioning

confidence: 99%

“…Conserved C-repeat regions of the M proteins have been shown to evoke protective immune responses after mucosal administration (3,7,14). The type-specific N-terminal regions of M proteins contain epitopes that evoke serum bactericidal antibodies after parenteral administration (2). It was previously shown that recombinant multivalent M protein-based vaccines containing N-terminal peptides from 4, 6, 8, and 26 different M serotypes evoke opsonic antibodies to the respective vaccine strains after intramuscular injection (10,12,13,17).…”

mentioning

confidence: 99%

Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections

Hall

Stroop²,

Hu³

et al. 2004

Infect Immun

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We have previously shown that a hexavalent group A streptococcal M protein-based vaccine evoked bactericidal antibodies after intramuscular injection. In the present study, we show that the hexavalent vaccine formulated with several different mucosal adjuvants and delivered intranasally induced serum and salivary antibodies that protected mice from intranasal challenge infections with virulent group A streptococci. The hexavalent vaccine was formulated with liposomes with or without monophosphorylated lipid A (MPL), cholera toxin B subunit with or without holotoxin, or proteosomes from Neisseria meningitidis outer membrane proteins complexed with lipopolysaccharide from Shigella flexneri. Intranasal immunization with the hexavalent vaccine mixed with these adjuvants resulted in significant levels of antibodies in serum 2 weeks after the final dose. Mean serum antibody titers were equivalent in all groups of mice except those that were immunized with hexavalent protein plus liposomes without MPL, which were significantly lower. Salivary antibodies were also detected in mice that received the vaccine formulated with the four strongest adjuvants. T-cell proliferative assays and cytokine assays using lymphocytes from cervical lymph nodes and spleens from mice immunized with the hexavalent vaccine formulated with proteosomes indicated the presence of hexavalent protein-specific T cells and a Th1-weighted mixed Th1-Th2 cytokine profile. Intranasal immunization with adjuvanted formulations of the hexavalent vaccine resulted in significant levels of protection (80 to 100%) following intranasal challenge infections with type 24 group A streptococci. Our results indicate that intranasal delivery of adjuvanted multivalent M protein vaccines induces protective antibody responses and may provide an alternative to parenteral vaccine formulations.

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“…87 However, work by Dale and Beachey identified epitopes of the M protein that are opsonic, without being cross-reactive, enabling the development of recombinant protein constructs that can elicit functional immunity. 88 Recent work from our group demonstrated that vaccination against influenza virus can prevent severe pneumonia and death in a mouse model of superinfection. 89 This model is now being used to evaluate the contributions of vaccine-induced immunity toward S. pyogenes with regard to protection against super-infection, using a hexavalent M protein vaccine.…”

Section: Correlating Bacterial Vaccine Use With Reduced Secondary Pnementioning

confidence: 99%

Correlates of vaccine protection from influenza and its complications

McCullers

Huber

2012

Human Vaccines & Immunotherapeutics

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Protective and autoimmune epitopes of streptococcal M proteins

Cited by 44 publications

References 21 publications

B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis

B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis

Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections

Correlates of vaccine protection from influenza and its complications

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