M-protein based vaccine induces immunogenicity and protection from Streptococcus pyogenes when delivered on a high-density microarray patch (HD-MAP)

Mills, Jamie-Lee; Flores, Cesar M. Jayashi; Reynolds, Simone; Wun, Christine; Calcutt, Ainslie; Baker, S. Ben; Murugappan, Senthil; Depelsenaire, Alexandra C. I.; Dooley, Jessica; Fahey, Paul; Forster, Angus; Pandey, Manisha; Good, Michael F.

doi:10.1038/s41541-020-00222-2

Cited by 14 publications

(11 citation statements)

References 63 publications

(118 reference statements)

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“…84 Currently, the J8-DT/HD-MAP vaccine appears promising as it has been demonstrated to significantly reduce the number of Streptococcus pyogenes colony forming units in animal studies. 85 There are no established GAS clinical trials in humans at the time of this review. 86 …”

Section: Non-antibiotic Measuresmentioning

confidence: 99%

Recurrent Cellulitis: Who is at Risk and How Effective is Antibiotic Prophylaxis?

Ong¹,

Dotel²,

Ngian³

2022

IJGM

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Recurrent cellulitis following successful treatment is common and prevention should be a major component in the management of cellulitis. Conditions that increase the risk of recurrence include chronic edema, venous disease, dermatomycosis and obesity. These risk factors should be actively managed as further episodes of cellulitis increases the risk of recurrence. The role of non-antibiotic measures is important and should be first-line in prevention. Antibiotic prophylaxis is effective, but its role is limited to non-purulent cellulitis where risk factors are appropriately managed.

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Section: Non-antibiotic Measuresmentioning

confidence: 99%

Recurrent Cellulitis: Who is at Risk and How Effective is Antibiotic Prophylaxis?

Ong¹,

Dotel²,

Ngian³

2022

IJGM

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“…Notably, antibody isotype class switching from IgM to mouse IgG3 constant regions was proven to be driven by the frequent exposure to polysaccharide antigens [45, 46]. A strong IgG1 response was observed in humans exposed to polysaccharides from pneumococcal pathogens [35] and increased IgG2a and IgG2b levels were detected in mice exposed to M protein-based vaccines from Streptococcus pyogenes [47].…”

Section: Discussion and Concluding Remarksmentioning

confidence: 99%

Recombinant Group A Carbohydrate backbone embedded into Outer Membrane Vesicles is a potent vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Castro

Thomson

Zorzoli

et al. 2021

Preprint

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BackgroundGroup A Streptococcus (GAS) are responsible for a wide range of human-exclusive infections, annually killing more than 500,000 people. Antibiotic resistance incidence of invasive GAS tripled in the past decade and emphasises the need to develop a universal GAS vaccine. We have produced, for the first time, a recombinant polyrhamnose backbone (pRha), a validated universal GAS vaccine candidate. E. coli outer membrane vesicles (OMVs) carrying pRha were investigated for their immunogenicity and efficacy in an animal model.MethodsOMVs decorated with pRha were administered to C57BL/6J mouse and rabbit models. Flow cytometry, ELISA, Luminex, immunofluorescence microscopy and serum bactericidal assay assays were conducted to investigate the ability of pRha-specific antibodies to recognise and kill clinical (hypervirulent) GAS strains.ResultsOur results suggest that pRha-OMVs induce specific antibodies which recognise Group A Carbohydrate (GAC) from S pyogenes and S. dysgalactiae subsp. equisimilis. Increased IgG levels correlate with increased bactericidal killing of the hypervirulent GAS M89 strain. Elevated IL-17a from pRha-OMV-immunised splenocytes indicates possible stimulation of long-term memory immune cells.ConclusionWe are the first to report efficacy and potency of this unique, exogenously produced polysaccharide, pRha, in the induction of humoral-mediated immune responses to GAS.TopicStreptococcus pyogenes, immunoglobulins, polysaccharides, opsonophagocytosis, acute rheumatic fever, M protein, invasive Group A Streptococcus, hyaluronic acid

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“…Additionally, the antigenic nature of S. pyogenes M proteins is well-recognized [ 65 , 66 ], and anti-M protein responses are associated with host protection against repeat infection by strains of the same M type [ 67 , 68 ]. Regarding S. canis , antisera against SCM has been detected in diseased cats [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Models of Streptococcus canis Colonization and Disease Reveal Modest Contributions of M-Like (SCM) Protein

et al. 2021

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Streptococcus canis is a common colonizing bacterium of the urogenital tract of cats and dogs that can also cause invasive disease in these animal populations and in humans. Although the virulence mechanisms of S. canis are not well-characterized, an M-like protein, SCM, has recently identified been as a potential virulence factor. SCM is a surface-associated protein that binds to host plasminogen and IgGs suggesting its possible importance in host-pathogen interactions. In this study, we developed in vitro and ex vivo blood component models and murine models of S. canis vaginal colonization, systemic infection, and dermal infection to compare the virulence potential of the zoonotic S. canis vaginal isolate G361 and its isogenic SCM-deficient mutant (G361∆scm). We found that while S. canis establishes vaginal colonization and causes invasive disease in vivo, the contribution of the SCM protein to virulence phenotypes in these models is modest. We conclude that SCM is dispensable for invasive disease in murine models and for resistance to human blood components ex vivo, but may contribute to mucosal persistence, highlighting a potential contribution to the recently appreciated genetic diversity of SCM across strains and hosts.

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M-protein based vaccine induces immunogenicity and protection from Streptococcus pyogenes when delivered on a high-density microarray patch (HD-MAP)

Cited by 14 publications

References 63 publications

Recurrent Cellulitis: Who is at Risk and How Effective is Antibiotic Prophylaxis?

Recurrent Cellulitis: Who is at Risk and How Effective is Antibiotic Prophylaxis?

Recombinant Group A Carbohydrate backbone embedded into Outer Membrane Vesicles is a potent vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis

Novel Models of Streptococcus canis Colonization and Disease Reveal Modest Contributions of M-Like (SCM) Protein

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