scholarly journals A Multicomponent Vaccine Provides Immunity against Local and Systemic Infections by Group A Streptococcus across Serotypes

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Shuai Bi ◽  
Meiyi Xu ◽  
Ya Zhou ◽  
Xinxin Xing ◽  
Adong Shen ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th17 Response ◽  
Different Types ◽  
Group A ◽  
Large Repertoire ◽  
Multicomponent Vaccine

ABSTRACT Group A streptococcus (GAS) species are responsible for a broad spectrum of human diseases, ranging from superficial to invasive infections, and are associated with autoimmune disorders. There is no commercial vaccine against GAS. The clinical manifestations of GAS infection may be attributable to the large repertoire of virulence factors used selectively in different types of GAS disease. Here, we selected five molecules, highly conserved among GAS serotypes, and involved in different pathogenic mechanisms, as a multicomponent vaccine, 5CP. Intranasal (i.n.) immunization with 5CP protected mice against both mucosal and systemic GAS infection across serotypes; the protection lasted at least 6 months. Immunization of mice with 5CP constrained skin lesion development and accelerated lesion recovery. Flow cytometry and enzyme-linked immunosorbent assay analyses revealed that 5CP induced Th17 and antibody responses locally and systemically; however, the Th17 response induced by 5CP resolved more quickly than that to GAS when challenge bacteria were cleared, suggesting that 5CP is less likely to cause autoimmune responses. These findings support that immunization through the i.n. route targeting multiple nonredundant virulence factors can induce immunity against different types of GAS disease and represents an alternative strategy for GAS vaccine development, with favorable efficacy, coverage, duration, and safety. IMPORTANCE GAS is among the most common human pathogens and causes a wide variety of diseases, likely more than any other microorganism. The diverse clinical manifestations of GAS may be attributable to its large repertoire of virulence factors that are selectively and synergistically involved in streptococcal pathogenesis. To date, GAS vaccines have not been successful due to multiple serotypes and postinfection sequelae associated with autoimmunity. In this study, five conserved virulence factors that are involved in GAS pathogenesis were used as a combined vaccine. Intranasal immunization with this vaccine induced humoral and cellular immune responses across GAS serotypes and protected against mucosal, systemic, and skin infections. The significance of this work is to demonstrate that the efficacy of GAS vaccines can be achieved by including multiple nonredundant critical virulence factors and inducing local and systemic immunity. The strategy also provides valuable insights for vaccine development against other pathogens.

scholarly journals Molecular Epidemiology of Group A Streptococcus Infections in The Gambia

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 124
Author(s):  
Sona Jabang ◽  
Annette Erhart ◽  
Saffiatou Darboe ◽  
Aru-Kumba Baldeh ◽  
Valerie Delforge ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Epidemiological Data ◽  
The Gambia ◽  
Strain Diversity ◽  
Group A ◽  
Considerable Strain

Molecular epidemiological data on Group A Streptococcus (GAS) infection in Africa is scarce. We characterized the emm-types and emm-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we used a newly published primer for emm-typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection.

Invasive M1T1 group A Streptococcus undergoes a phase-shift in vivo to prevent proteolytic degradation of multiple virulence factors by SpeB

2003 ◽  
Vol 51 (1) ◽  
pp. 123-134 ◽  
Author(s):  
Ramy K. Aziz ◽  
Michael J. Pabst ◽  
Arthur Jeng ◽  
Rita Kansal ◽  
Donald. E. Low ◽  
...  
Keyword(s):  
Phase Shift ◽  
Virulence Factors ◽  
Group A Streptococcus ◽  
Proteolytic Degradation ◽  
Group A

scholarly journals Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

2019 ◽  
Vol 216 (7) ◽  
pp. 1615-1629 ◽  
Author(s):  
Andreas Naegeli ◽  
Eleni Bratanis ◽  
Christofer Karlsson ◽  
Oonagh Shannon ◽  
Raja Kalluru ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Infection ◽  
Invasive Infections ◽  
Life Threatening ◽  
Group A ◽  
Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

scholarly journals Survey of the bp/tee genes from clinical group A streptococcus isolates in New Zealand – implications for vaccine development

2014 ◽  
Vol 63 (12) ◽  
pp. 1670-1678 ◽  
Author(s):  
John D. Steemson ◽  
Nicole J. Moreland ◽  
Deborah Williamson ◽  
Julie Morgan ◽  
Philip E. Carter ◽  
...  
Keyword(s):  
New Zealand ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
T Antigen ◽  
Clinical Group ◽  
Wide Range ◽  
Life Threatening ◽  
Group A ◽  
The Individual

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (>97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/T-antigen as a vaccine target.

scholarly journals Incompetence of Neutrophils to Invasive Group A streptococcus Is Attributed to Induction of Plural Virulence Factors by Dysfunction of a Regulator

PLoS ONE ◽  
2008 ◽  
Vol 3 (10) ◽  
pp. e3455 ◽  
Author(s):  
Manabu Ato ◽  
Tadayoshi Ikebe ◽  
Hiroki Kawabata ◽  
Toshitada Takemori ◽  
Haruo Watanabe
Keyword(s):  
Virulence Factors ◽  
Group A Streptococcus ◽  
Invasive Group ◽  
Group A

scholarly journals SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Martínez-Flores ◽  
Jesús Zepeda-Cervantes ◽  
Adolfo Cruz-Reséndiz ◽  
Sergio Aguirre-Sampieri ◽  
Alicia Sampieri ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Clinical Manifestations ◽  
Receptor Binding Domain ◽  
Current Vaccine ◽  
Main Target ◽  
Different Types ◽  
Antigenic Domains

Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants.

scholarly journals Immunogenicity Assessment of Different Segments and Domains of Group A Streptococcal C5a Peptidase and Their Application Potential as Carrier Protein for Glycoconjugate Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 139
Author(s):  
Guirong Wang ◽  
Jielin Zhao ◽  
Yisheng Zhao ◽  
Subo Wang ◽  
Shaojie Feng ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Group A Streptococcus ◽  
Carrier Protein ◽  
Cell Surfaces ◽  
Gas Cell ◽  
Subunit Vaccines ◽  
Immunogenicity Assessment ◽  
Group A ◽  
Application Potential ◽  
Glycoconjugate Vaccine

Group A streptococcal C5a peptidase (ScpA) is a highly conserved surface virulence factor present on group A streptococcus (GAS) cell surfaces. It has attracted much more attention as a promising antigenic target for GAS vaccine development due to its high antigenicity to stimulate specific and immunoprotective antibodies. In this study, a series of segments of ScpA were rationally designed according to the functional domains described in its crystal structure, efficiently prepared and immunologically evaluated so as to assess their potential as antigens for the development of subunit vaccines. Immunological studies revealed that Fn, Fn2, and rsScpA193 proteins were promising antigen candidates worthy for further exploration. In addition, the potential of Fn and Fn2 as carrier proteins to formulate effective glycoconjugate vaccine was also investigated.

scholarly journals Phosphorylation of the Group A Streptococcal CovR Response Regulator Causes Dimerization and Promoter-Specific Recruitment by RNA Polymerase

2006 ◽  
Vol 188 (13) ◽  
pp. 4620-4626 ◽  
Author(s):  
Asiya A. Gusa ◽  
Jinxin Gao ◽  
Virginia Stringer ◽  
Gordon Churchward ◽  
June R. Scott
Keyword(s):  
Rna Polymerase ◽  
Virulence Factors ◽  
Group A Streptococcus ◽  
Response Regulator ◽  
Regulatory System ◽  
In Vitro Transcription ◽  
Wild Type ◽  
Group A ◽  
The Difference

ABSTRACT The group A streptococcus (GAS), Streptococcus pyogenes, is an important human pathogen that causes infections ranging in severity from self-limiting pharyngitis to severe invasive diseases that are associated with significant morbidity and mortality. The pathogenic effects of GAS are mediated by the expression of virulence factors, one of which is the hyaluronic acid capsule (encoded by genes in the has operon). The expression of these virulence factors is controlled by the CovR/S (CsrR/S) two-component regulatory system of GAS which regulates, directly or indirectly, the expression of about 15% of the genome. CovR is a member of the OmpR/PhoB family of transcriptional regulators. Here we show that phosphorylation by acetyl phosphate results in dimerization of CovR. Dimerization was not observed using a D53A mutant of CovR, indicating that D53 is the site of phosphorylation in CovR. Phosphorylation stimulated binding of CovR to a DNA fragment containing the promoter of the has operon (Phas) approximately twofold. Binding of CovR D53A mutant protein to Phas was indistinguishable from the binding of wild-type unphosphorylated CovR. In vitro transcription, using purified GAS RNA polymerase, showed that wild-type CovR repressed transcription, and repression was stimulated more than sixfold by phosphorylation. In the presence of RNA polymerase, binding at Phas of phosphorylated, but not unphosphorylated, CovR was stimulated about fourfold, which accounts for the difference in the effect of phosphorylation on repression versus DNA binding. Thus, regulation of Phas by CovR is direct, and the degree of repression of Phas is controlled by the phosphorylation of CovR.

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