scholarly journals Recent Advances in the Development of Peptide Vaccines and Their Delivery Systems Against Group A Streptococcus

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 58 ◽  
Author(s):  
Azuar ◽  
Jin ◽  
Mukaida ◽  
Hussein ◽  
Toth ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Group A Streptococcus ◽  
Delivery Systems ◽  
Peptide Vaccines ◽  
Peptide Epitope ◽  
The Public ◽  
Life Threatening ◽  
Group A ◽  
Preclinical And Clinical Studies ◽  
Traditional Approaches

Group A Streptococcus (GAS) infection can cause a variety of diseases in humans, ranging from common sore throats and skin infections, to more invasive diseases and life-threatening post-infectious diseases, such as rheumatic fever and rheumatic heart disease. Although research has been ongoing since 1923, vaccines against GAS are still not available to the public. Traditional approaches taken to develop vaccines for GAS failed due to poor efficacy and safety. Fortunately, headway has been made and modern subunit vaccines that administer minimal bacterial components provide an opportunity to finally overcome previous hurdles in GAS vaccine development. This review details the major antigens and strategies used for GAS vaccine development. The combination of antigen selection, peptide epitope modification and delivery systems have resulted in the discovery of promising peptide vaccines against GAS; these are currently in preclinical and clinical studies.

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 Invasive group A Streptococcus disease in Australian children: 2016 to 2018 – a descriptive cohort study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jane Oliver ◽  
◽  
Elise Thielemans ◽  
Alissa McMinn ◽  
Ciara Baker ◽  
...  
Keyword(s):  
Disease Surveillance ◽  
Vaccine Development ◽  
Group A Streptococcus ◽  
Invasive Disease ◽  
Incidence Rates ◽  
Surveillance Systems ◽  
Invasive Group ◽  
Australian State ◽  
Life Threatening ◽  
Group A

Abstract Objectives Invasive group A Streptococcus (iGAS) disease is serious and sometimes life-threatening. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network collects voluntary notifications from seven major Australian paediatric hospitals on patients with certain conditions, including iGAS disease. Our aims were to: 1) Describe the epidemiological distribution of paediatric iGAS disease in Australia and correlate this with influenza notifications, 2) Identify GAS strains commonly associated with invasive disease in children. Methods IGAS and influenza notification data were obtained (from the PAEDS Network and the Australian Institute of Health and Welfare, respectively, for the period 1 July 2016 to 30 June 2018). Included iGAS patients had GAS isolated from a normally sterile body site. Data were described according to selected clinical and demographic characteristics, including by age group and Australian State, with proportions and minimum incidence rates estimated. Results A total of 181 patients were identified, with most (115, 63.5%) <5 years old. The mean annual minimum incidence rate was 1.6 (95% confidence interval: 1.1–2.3) per 100,000 children across the study period. An epidemiological correlation with the seasonal burden of influenza was noted. Contact prophylaxis was not consistently offered. Of 96 patients with emm-typing results available, 72.9% showed emm-1, −4 or − 12. Conclusions Robust surveillance systems and cohesive patient management guidelines are needed. Making iGAS disease nationally notifiable would help facilitate this. Influenza vaccination may contribute to reducing seasonal increases in iGAS incidence. The burden of disease emphasises the need for ongoing progress in GAS vaccine development.

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.

An Outbreak of Fatal Nosocomial Infections Due to Group A Streptococcus on a Medical Ward

1996 ◽  
Vol 17 (7) ◽  
pp. 429-431 ◽  
Author(s):  
L. Ramage ◽  
K. Green ◽  
D. Pyskir ◽  
A.E. Simor
Keyword(s):  
Nosocomial Infections ◽  
Community Hospital ◽  
Group A Streptococcus ◽  
Hospital Setting ◽  
Streptococcal Infections ◽  
Severe Group ◽  
Life Threatening ◽  
Group A ◽  
Spread Of Infection ◽  
Dna Profiles

AbstractGroup A streptococcus is an uncommon but important cause of nosocomial infections. Outbreaks of infection most often have occurred in surgical or obstetrical patients. We describe an outbreak of severe group A streptococcal infections that occurred on a medical unit of a community hospital. Within an 8-day period, three patients developed fatal nosocomial skin and soft-tissue infection due to group A streptococcus. Three nurses who had provided care to one or more of these patients subsequently developed strepto-coccal pharyngitis, and three other nurses were treated with antibiotics for pharyngitis (cultures not obtained). Patient isolates were serotype M-nontypeable, T-11, opacity factor-positive, and shared identical DNA profiles when typed by pulsed-field gel electrophoresis; staff isolates were not available for typing. To prevent further spread of infection, the ward was closed to new admissions, and symptomatic staff were treated with antibiotics and relieved of patient-care duties. This outbreak demonstrates the ability of group A streptococcus to spread rapidly in a hospital setting and to cause severe life-threatening disease in hospitalized patients.

scholarly journals Twenty-first century vaccines

2011 ◽  
Vol 366 (1579) ◽  
pp. 2756-2758 ◽  
Author(s):  
Rino Rappuoli
Keyword(s):  
Infectious Diseases ◽  
Group A Streptococcus ◽  
Emerging Infectious Diseases ◽  
Meningococcal Meningitis ◽  
First Century ◽  
The Public ◽  
Group A ◽  
Disability Free Life Expectancy ◽  
Twenty First Century ◽  
Syncytial Virus

In the twentieth century, vaccination has been possibly the greatest revolution in health. Together with hygiene and antibiotics, vaccination led to the elimination of many childhood infectious diseases and contributed to the increase in disability-free life expectancy that in Western societies rose from 50 to 78–85 years (Crimmins, E. M. & Finch, C. E. 2006 Proc. Natl Acad. Sci. USA 103, 498–503; Kirkwood, T. B. 2008 Nat. Med 10, 1177–1185). In the twenty-first century, vaccination will be expected to eliminate the remaining childhood infectious diseases, such as meningococcal meningitis, respiratory syncytial virus, group A streptococcus, and will address the health challenges of this century such as those associated with ageing, antibiotic resistance, emerging infectious diseases and poverty. However, for this to happen, we need to increase the public trust in vaccination so that vaccines can be perceived as the best insurance against most diseases across all ages.

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 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.

Necrotizing Fasciitis Caused by Group A Streptococcus: Case Report and Therapy Update

2002 ◽  
Vol 15 (3) ◽  
pp. 290-296 ◽  
Author(s):  
Margareth Larose-Pierre ◽  
John J. Scrivens ◽  
Daryl Norwood ◽  
Leonard Rappa
Keyword(s):  
Necrotizing Fasciitis ◽  
Group A Streptococcus ◽  
Supportive Therapy ◽  
Morbidity And Mortality ◽  
Treatment Modalities ◽  
Illustrative Case ◽  
Toxic Shock ◽  
Therapeutic Modalities ◽  
Life Threatening ◽  
Group A

Necrotizing fasciitis is a life-threatening infection that affects the fascia and fat tissue underlying the skin. The diagnosis is often difficult because subcutaneous changes may not be readily apparent. Toxin-producing bacteria are usually the cause, with group A streptococcus (GAS) or Streptococcus pyogenes being responsible for a significant portion of the morbidity and mortality associated with this infection. The mortality rate associated with necrotizing fasciitis varies between 30% and 60%. Toxic shock-like syndrome and multisystem organ failure are the usual causes of death. Early diagnosis and surgery have been associated with decreased morbidity and mortality, and appropriate antimicrobial (eg, penicillin plus clindamycin) and supportive therapy is of utmost importance. Intravenous immunoglobulin and hyperbaric oxygen therapy may be beneficial in treating the infection; however, these 2 therapies require further research. Clinicians need to familiarize themselves with the disease and the different treatment modalities to be able to make the appropriate therapeutic decision. The optimal treatment of necrotizing fasciitis still remains a challenge today. This article presents an illustrative case with a brief overview of necrotizing fasciitis, and the current therapeutic modalities used in the management of the disease.

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