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 Dynamics of anti-M antibody response in a mouse model following intranasal infection with group A Streptococcus M-18

2005 ◽  
Vol 54 (3) ◽  
pp. 305-308 ◽  
Author(s):  
Paul Gladstone ◽  
George Varghese ◽  
K N Brahmadathan
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Antibody Response ◽  
Indirect Elisa ◽  
Group A Streptococcus ◽  
Swiss Albino Mouse ◽  
Intranasal Infection ◽  
Model Following ◽  
Antibody Titres ◽  
Group A

Dynamics of anti-M antibody response following intranasal infection with group A Streptococcus (GAS) M-18 were investigated in a Swiss albino mouse model. Mice arranged in three groups were inoculated intranasally with 2.0 × 107 c.f.u. ml−1 of GAS M-18 on 1, 2 alternate and 3 alternate days. Plasma collected from the retro-orbital plexus was tested for antibodies by an in-house indirect ELISA. The antibody titres of the plasma samples varied from 1 : 8 to 1 : 1024 in the 1 day dose, from 1 : 4 to 1 : 256 in the 2 day dose and from 1 : 4 to 1 : 128 in the 3 day dose. Peak titres were seen on day 42 or 56 and in all cases the titres had declined by day 84. Swiss albino mouse can thus serve as a useful animal model to study different aspects of type-specific anti-M immune responses against GAS disease when designing candidate streptococcal vaccines.

M-Protein-derived Conformational Peptide Epitope Vaccine Candidate against Group A Streptococcus

2013 ◽  
Vol 10 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Mariusz Skwarczynski ◽  
Khairul A. Kamaruzaman ◽  
Saranya Srinivasan ◽  
Mehfuz Zaman ◽  
I-Chun Lin ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Group A Streptococcus ◽  
M Protein ◽  
Epitope Vaccine ◽  
Peptide Epitope ◽  
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 Development of Polyelectrolyte Complexes for the Delivery of Peptide-Based Subunit Vaccines against Group A Streptococcus

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 823 ◽  
Author(s):  
Lili Zhao ◽  
Wanli Jin ◽  
Jazmina Gonzalez Cruz ◽  
Nirmal Marasini ◽  
Zeinab G. Khalil ◽  
...  
Keyword(s):  
Immune Responses ◽  
Subunit Vaccine ◽  
Group A Streptococcus ◽  
Vaccine Delivery ◽  
Surface Charges ◽  
Subunit Vaccines ◽  
Polyelectrolyte Complexes ◽  
Humoral Immune ◽  
Anionic Polymers ◽  
Group A

Peptide subunit vaccines hold great potential compared to traditional vaccines. However, peptides alone are poorly immunogenic. Therefore, it is of great importance that a vaccine delivery platform and/or adjuvant that enhances the immunogenicity of peptide antigens is developed. Here, we report the development of two different systems for the delivery of lipopeptide subunit vaccine (LCP-1) against group A streptococcus: polymer-coated liposomes and polyelectrolyte complexes (PECs). First, LCP-1-loaded and alginate/trimethyl chitosan (TMC)-coated liposomes (Lip-1) and LCP-1/alginate/TMC PECs (PEC-1) were examined for their ability to trigger required immune responses in outbred Swiss mice; PEC-1 induced stronger humoral immune responses than Lip-1. To further assess the adjuvanting effect of anionic polymers in PECs, a series of PECs (PEC-1 to PEC-5) were prepared by mixing LCP-1 with different anionic polymers, namely alginate, chondroitin sulfate, dextran, hyaluronic acid, and heparin, then coated with TMC. All produced PECs had similar particle sizes (around 200 nm) and surface charges (around + 30 mV). Notably, PEC-5, which contained heparin, induced higher antigen-specific systemic IgG and mucosal IgA titers than all other PECs. PEC systems, especially when containing heparin and TMC, could function as a promising platform for peptide-based subunit vaccine delivery for intranasal administration.

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 Regulatory Role of GSK-3βon NF-κB, Nitric Oxide, and TNF-αin Group A Streptococcal Infection

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Tzu Chang ◽  
Chia-Ling Chen ◽  
Chiou-Feng Lin ◽  
Shiou-Ling Lu ◽  
Miao-Huei Cheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mouse Model ◽  
Group A Streptococcus ◽  
Glycogen Synthase ◽  
Critical Issue ◽  
No Production ◽  
Group A ◽  
Oxide Synthase

Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β(GSK-3β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3βin GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3βoccurred after GAS infection, and inhibition of GSK-3βreduced iNOS expression and NO production. Furthermore, GSK-3βinhibitors reduced NF-κB activation and subsequent TNF-αproduction, which indicates that GSK-3βacts upstream of NF-κB in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3βinhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-αand improved the survival rate. The inhibition of GSK-3βto moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

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 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.

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
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