scholarly journals Protective immunity induced by an intranasal multivalent vaccine comprising 10 Lactococcus lactis strains expressing highly prevalent M-protein antigens derived from Group A Streptococcus

2018 ◽  
Vol 62 (6) ◽  
pp. 395-404 ◽  
Author(s):  
Aniela Wozniak ◽  
Natalia Scioscia ◽  
Patricia C. García ◽  
James B. Dale ◽  
Braulio A. Paillavil ◽  
...  
Keyword(s):  
Lactococcus Lactis ◽  
Protective Immunity ◽  
Group A Streptococcus ◽  
M Protein ◽  
Protein Antigens ◽  
Multivalent Vaccine ◽  
Group A

scholarly journals Similar Ability of FbaA with M Protein to Elicit Protective Immunity Against Group A Streptococcus Challenge in Mice

2009 ◽  
Vol 6 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Cuiqing Ma ◽  
Caihong Li ◽  
Xiurong Wang ◽  
Ruihong Zeng ◽  
Xiaolin Yin ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Group A Streptococcus ◽  
M Protein ◽  
Group A

scholarly journals Host Pathways of Hemostasis that Regulate Group A Streptococcus pyogenes Pathogenicity

2020 ◽  
Vol 21 (2) ◽  
pp. 193-201
Author(s):  
Victoria A. Ploplis ◽  
Francis J. Castellino
Keyword(s):  
Streptococcus Pyogenes ◽  
Inflammatory Responses ◽  
Group A Streptococcus ◽  
Protein A ◽  
M Protein ◽  
Severe Group ◽  
Group A ◽  
Flow Through ◽  
Hallmark Feature ◽  
Major Target

A hallmark feature of severe Group A Streptococcus pyogenes (GAS) infection is dysregulated hemostasis. Hemostasis is the primary pathway for regulating blood flow through events that contribute towards clot formation and its dissolution. However, a number of studies have identified components of hemostasis in regulating survival and dissemination of GAS. Several proteins have been identified on the surface of GAS and they serve to either facilitate invasion to host distal sites or regulate inflammatory responses to the pathogen. GAS M-protein, a surface-exposed virulence factor, appears to be a major target for interactions with host hemostasis proteins. These interactions mediate biochemical events both on the surface of GAS and in the solution when M-protein is released into the surrounding environment through shedding or regulated proteolytic processes that dictate the fate of this pathogen. A thorough understanding of the mechanisms associated with these interactions could lead to novel approaches for altering the course of GAS pathogenicity.

scholarly journals Erratum: Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein

2017 ◽  
Vol 2 (7) ◽  
Author(s):  
Cosmo Z. Buffalo ◽  
Adrian J. Bahn-Suh ◽  
Sophia P. Hirakis ◽  
Tapan Biswas ◽  
Rommie E. Amaro ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Binding Protein ◽  
M Protein ◽  
Group A

scholarly journals Clinical and Microbiological Responses of Volunteers to Combined Intranasal and Oral Inoculation with a Streptococcus gordonii Carrier Strain Intended for Future Use as a Group A Streptococcus Vaccine

2005 ◽  
Vol 73 (4) ◽  
pp. 2360-2366 ◽  
Author(s):  
Karen L. Kotloff ◽  
Steven S. Wasserman ◽  
Kevin F. Jones ◽  
Sofie Livio ◽  
Dennis E. Hruby ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Group A Streptococcus ◽  
Nasal Congestion ◽  
Vaccine Vector ◽  
Mucosal Vaccine ◽  
Respiratory Pathogens ◽  
Streptococcus Gordonii ◽  
Protein Antigens ◽  
Oral Inoculation ◽  
Group A

ABSTRACT Streptococcus gordonii shows promise as a live mucosal vaccine vector for immunization against respiratory pathogens. In preparation for clinical trials to evaluate S. gordonii engineered to express group A streptococcal M protein antigens, we characterized the responses of 150 healthy volunteers to combined nasal and oral inoculation with approximately 1.5 × 109 CFU of SP204(1-1), an S. gordonii strain not bearing vaccine antigens. SP204(1-1) was selected for resistance to streptomycin and 5-fluoro-2-deoxyuridine to distinguish it from indigenous flora. In two antibiotic treatment studies, we performed serial culturing of nose, mouth, and saliva samples from 120 subjects treated with azithromycin beginning 5 days after inoculation to determine whether SP204(1-1) could be rapidly eliminated should safety concerns arise. A natural history study was performed to assess the time until spontaneous eradication in the remaining 30 subjects, who did not receive the antibiotic and who were monitored with repeated culturing for 14 weeks after inoculation. SP204(1-1) was generally well tolerated. Symptoms reported most often within 5 days of inoculation were nasal congestion (36%), headache (30%), and sore throat (19%). The strain was detected by culturing in 98% of subjects. A single dose of azithromycin eliminated colonization in 95% of subjects; all subjects receiving a 5-day course of an antibiotic showed clearance by day 11. Without the antibiotic, 82% of subjects showed spontaneous eradication of the implanted strain within 7 days, and all showed clearance by 35 days. The results of these clinical trials provide encouragement that the use of S. gordonii as a live mucosal vaccine vector is a feasible strategy.

scholarly journals Conversion of an M- group A streptococcus to M+ by transfer of a plasmid containing an M6 gene.

1986 ◽  
Vol 164 (5) ◽  
pp. 1641-1651 ◽  
Author(s):  
J R Scott ◽  
P C Guenthner ◽  
L M Malone ◽  
V A Fischetti
Keyword(s):  
Structural Gene ◽  
Human Blood ◽  
Group A Streptococcus ◽  
M Protein ◽  
Gene Encoding ◽  
Hyperimmune Serum ◽  
Amino Terminal ◽  
Group A ◽  
Hyperimmune Rabbit ◽  
Streptococcal Strain

An M28-derived group A streptococcal strain deleted for the gene encoding M protein was converted to M+ by introduction of a plasmid carrying emm6, the structural gene for type 6 M protein from strain D471. The reconstituted M+ strain, JRS2, resists phagocytosis in human blood and is opsonized by anti-M6 hyperimmune serum, but not by anti-M28 serum. Immunofluorescent microscopy and ELISA demonstrate the presence of M protein on its surface. In addition, JRS2 removes opsonic antibodies from hyperimmune rabbit sera generated by immunization with purified ColiM6 protein and with a synthetic amino-terminal peptide derived from M6. Immunization of rabbits with JRS2 generates opsonic anti-M6 antibodies. These results indicate that the cloned emm6 gene contains the information necessary to convert a phagocytosis-sensitive streptococcus to phagocytosis resistance. Furthermore, it also contains the determinants for M type specificity and those required to elicit opsonic antibodies. It thus appears to determine all the traits associated with M protein.

scholarly journals Structure-based group A streptococcal vaccine design: Helical wheel homology predicts antibody cross-reactivity among streptococcal M protein–derived peptides

2020 ◽  
Vol 295 (12) ◽  
pp. 3826-3836 ◽  
Author(s):  
Michelle P. Aranha ◽  
Thomas A. Penfound ◽  
Jay A. Spencer ◽  
Rupesh Agarwal ◽  
Jerome Baudry ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Coiled Coil ◽  
Cross Reactivity ◽  
M Protein ◽  
High Sequence Identity ◽  
Sequence Identity ◽  
Streptococcal M Protein ◽  
Helical Wheel ◽  
Group A ◽  
Immunological Assays

Group A streptococcus (Strep A) surface M protein, an α-helical coiled-coil dimer, is a vaccine target and a major determinant of streptococcal virulence. The sequence-variable N-terminal region of the M protein defines the M type and also contains epitopes that promote opsonophagocytic killing of streptococci. Recent reports have reported considerable cross-reactivity among different M types, suggesting the prospect of identifying cross-protective epitopes that would constitute a broadly protective multivalent vaccine against Strep A isolates. Here, we have used a combination of immunological assays, structural biology, and cheminformatics to construct a recombinant M protein–based vaccine that included six Strep A M peptides that were predicted to elicit antisera that would cross-react with an additional 15 nonvaccine M types of Strep A. Rabbit antisera against this recombinant vaccine cross-reacted with 10 of the 15 nonvaccine M peptides. Two of the five nonvaccine M peptides that did not cross-react shared high sequence identity (≥50%) with the vaccine peptides, implying that high sequence identity alone was insufficient for cross-reactivity among the M peptides. Additional structural analyses revealed that the sequence identity at corresponding polar helical-wheel heptad sites between vaccine and nonvaccine peptides accurately distinguishes cross-reactive from non–cross-reactive peptides. On the basis of these observations, we developed a scoring algorithm based on the sequence identity at polar heptad sites. When applied to all epidemiologically important M types, this algorithm should enable the selection of a minimal number of M peptide–based vaccine candidates that elicit broadly protective immunity against Strep A.

FbaA- and M protein-based multi-epitope vaccine elicits strong protective immune responses against group A streptococcus in mouse model

2014 ◽  
Vol 16 (5) ◽  
pp. 409-418 ◽  
Author(s):  
Cuiqing Ma ◽  
Zheng Liu ◽  
Wenjian Li ◽  
Xuesong Qian ◽  
Song Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Group A Streptococcus ◽  
M Protein ◽  
Epitope Vaccine ◽  
Group A

scholarly journals Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein

2016 ◽  
Vol 1 (11) ◽  
Author(s):  
Cosmo Z. Buffalo ◽  
Adrian J. Bahn-Suh ◽  
Sophia P. Hirakis ◽  
Tapan Biswas ◽  
Rommie E. Amaro ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Binding Protein ◽  
M Protein ◽  
Group A

scholarly journals The Mga Regulon but Not Deoxyribonuclease Sda1 of Invasive M1T1 Group A Streptococcus Contributes toIn VivoSelection of CovRS Mutations and Resistance to Innate Immune Killing Mechanisms

2015 ◽  
Vol 83 (11) ◽  
pp. 4293-4303 ◽  
Author(s):  
Guanghui Liu ◽  
Wenchao Feng ◽  
Dengfeng Li ◽  
Mengyao Liu ◽  
Daniel C. Nelson ◽  
...  
Keyword(s):  
Group A Streptococcus ◽  
Regulatory System ◽  
Innate Immune ◽  
M Protein ◽  
Content Type ◽  
Group A ◽  
Innate Immune Evasion ◽  
Selection Of

ABSTRACTInvasive M1T1 group AStreptococcus(GAS) can have a mutation in the regulatory system CovRS, and this mutation can render strains hypervirulent. Interestingly, via mechanisms that are not well understood, the host innate immune system's neutrophils select spontaneous M1T1 GAS CovRS hypervirulent mutants, thereby enhancing the pathogen's ability to evade immune killing. It has been reported that the DNase Sda1 is critical for the resistance of M1T1 strain 5448 to killing in human blood and provides pressure forin vivoselection of CovRS mutations. We reexamined the role of Sda1 in the selection of CovRS mutations and in GAS innate immune evasion. Deletion ofsda1or all DNase genes in M1T1 strain MGAS2221 did not alter emergence of CovRS mutants during murine infection. Deletion ofsda1in strain 5448 resulted in Δsda1mutants with (5448 Δsda1M+strain) and without (5448 Δsda1M−strain) M protein production. The 5448 Δsda1M+strain accumulated CovRS mutationsin vivoand resisted killing in the bloodstream, whereas the 5448 Δsda1M−strain lostin vivoselection of CovRS mutations and was sensitive to killing. The deletion ofemmand a spontaneous Mga mutation in MGAS2221 reduced and preventedin vivoselection for CovRS mutants, respectively. Thus, in contrast to previous reports, Sda1 is not critical forin vivoselection of invasive M1T1 CovRS mutants and GAS resistance to innate immune killing mechanisms. In contrast, M protein and other Mga-regulated proteins contribute to thein vivoselection of M1T1 GAS CovRS mutants. These findings advance the understanding of the progression of invasive M1T1 GAS infections.

scholarly journals M1 Protein Triggers a Phosphoinositide Cascade for Group A Streptococcus Invasion of Epithelial Cells

2003 ◽  
Vol 71 (10) ◽  
pp. 5823-5830 ◽  
Author(s):  
Sai Sudha Purushothaman ◽  
Beinan Wang ◽  
P. Patrick Cleary
Keyword(s):  
Epithelial Cells ◽  
Group A Streptococcus ◽  
Dominant Negative ◽  
M Protein ◽  
Lipid Kinase ◽  
Cytoskeletal Rearrangement ◽  
M1 Protein ◽  
Serovar Typhimurium ◽  
Group A

ABSTRACT Invasion of nonphagocytic cells by bacteria provides a favorable niche for persistence and evasion of host defenses and antibiotics. M protein is a major virulence factor because it promotes high-frequency invasion of epithelial cells by group A Streptococcus (GAS) and also renders the bacterium resistant to phagocytosis. In this study, we investigated the role of M1 protein from serotype M1 strain 90-226 in regulating mammalian signal transduction and cytoskeletal rearrangement for bacterial entry. LY294002 and wortmannin, which are inhibitors of phosphatidylinositol 3-kinase (PI 3-K) blocked invasion of epithelial cells by GAS by 75 and 80%, respectively, but failed to inhibit invasion by Salmonella enterica serovar Typhimurium. Also, epithelial cells transiently transfected with dominant negative p85 and p110 genes, the regulatory and catalytic subunits of PI 3-K, respectively, were less able to be invaded by GAS. To separate the influence of other streptococcal virulence factors from M protein, Lactococcus lactis was engineered to express M1 protein on its surface. L. lactis(pLM1) invaded epithelial cells efficiently in vitro, and PI 3-K inhibitors blocked 90% of this invasion. Purified soluble M1 protein stimulated the formation of stress fibers and actin tuffs on epithelial cells. LY294002 and wortmannin inhibited these cellular changes. A phosphoinositide analogue also inhibited the invasion of epithelial cells by GAS. Therefore, M1 protein, either directly or via bound fibronectin, initiates signals that depend on the lipid kinase PI 3-K pathway, which paves the way for cytoskeletal rearrangement that internalize the bacterium.

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