A Superficial Skin Scarification Method in Mice to Mimic Streptococcus pyogenes Skin Infection in Humans

Pandey, Manisha; Good, Michael F.

doi:10.1007/978-1-0716-0467-0_22

Cited by 5 publications

(5 citation statements)

References 9 publications

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“…The J8-DT vaccine candidate was recently evaluated for efficacy using high-density microarray patch delivery, demonstrating T H 1 cell/T H 2 cell induction and superior protection over intramuscular vaccination against GAS skin infection in mice 196 . Although not perfect representations of human GAS disease, valuable animal models for studying GAS vaccine candidates have been established and standardized, including a humanized mouse model for assessing invasive GAS infection 197 , a mouse skin infection model 198 and a non-human primate model of GAS pharyngitis 19 . Furthermore, a human GAS challenge model recently established by researchers in Australia is expected to reveal correlates of immune protection and accelerate clinical evaluation of current and future vaccines 20 .…”

Section: Outlook For Gas Vaccine Research and Developmentmentioning

confidence: 99%

Pathogenesis, epidemiology and control of Group A Streptococcus infection

et al. 2023

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Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. Fluctuating global GAS epidemiology is characterized by the emergence of new GAS clones, often associated with the acquisition of new virulence or antimicrobial determinants that are better adapted to the infection niche or averting host immunity. The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. The World Health Organization (WHO) has developed a GAS research and technology road Surface-bound virulence factors M protein. GAS is classified based on the sequence of the 5′ end of the gene encoding the M protein (emm). More than 220 emm genotypes have been identified 2 . The M protein is a dimeric coiled-coil fibrillar protein that extends from the bacterial cell wall 38 . It consists of a conserved Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author selfarchiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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Section: Outlook For Gas Vaccine Research and Developmentmentioning

confidence: 99%

Pathogenesis, epidemiology and control of Group A Streptococcus infection

et al. 2023

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“…Clinical scores are enumerated between 1–3 for ruffled fur, hunched posture, response to stimuli, level of consciousness/activity, respiration quality, eyes with excess secretions, blood in throat swabs and >15% weight loss in comparison pre-challenge. A score above 3 for any of these categories or a total score of above 14 instigates immediate euthanasia 45 . Mice are scored with observer blinded to the treatment.…”

Section: Resultsmentioning

confidence: 99%

“…For bacterial enumeration, all plates were incubated at 37 °C overnight, and individual hemolytic streptococcal colonies counted. Mice were monitored twice daily until the experiment end-point in accordance with established clinical scoring system 45 . The mice were scored with the observer blinded to the treatment.…”

Section: Methodsmentioning

confidence: 99%

A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils

Ozberk,

Zaman,

Lepletier

et al. 2023

Nat Commun

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Mucosally active subunit vaccines are an unmet clinical need due to lack of licensed immunostimulants suitable for vaccine antigens. Here, we show that intranasal administration of liposomes incorporating: the Streptococcus pyogenes peptide antigen, J8; diphtheria toxoid as a source of T cell help; and the immunostimulatory glycolipid, 3D(6-acyl) PHAD (PHAD), is able to induce long-lived humoral and cellular immunity. Mice genetically deficient in either mucosal antibodies or total antibodies are protected against S. pyogenes respiratory tract infection. Utilizing IL-17-deficient mice or depleting cellular subsets using antibodies, shows that the cellular responses encompassing, CD4+ T cells, IL-17, macrophages and neutrophils have important functions in vaccine-mediated mucosal immunity. Overall, these data demonstrate the utility of a mucosal vaccine platform to deliver multi-pronged protective responses against a highly virulent pathogen.

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“…The general health of the mice was monitored daily. Following the challenge, mice were monitored for signs of illness as per a score sheet approved by the Griffith University Animal Ethics Committee ( 68 ). The observer was blinded to the experimental groups.…”

Section: Methodsmentioning

confidence: 99%

Disruption of IL-17-mediated immunosurveillance in the respiratory mucosa results in invasive Streptococcus pyogenes infection

Mills,

Lepletier,

Ozberk

et al. 2024

Front. Immunol.

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IntroductionStreptococcus pyogenes is a Gram-positive pathogen that causes a significant global burden of skin pyoderma and pharyngitis. In some cases, infection can lead to severe invasive streptococcal diseases. Previous studies have shown that IL-17 deficiency in mice (IL-17−/−) can reduce S. pyogenes clearance from the mucosal surfaces. However, the effect of IL-17 on the development of severe invasive streptococcal disease has not yet been assessed.MethodsHere, we modeled single or repeated non-lethal intranasal (IN) S. pyogenes M1 strain infections in immunocompetent and IL-17−/− mice to assess bacterial colonization following a final IN or skin challenge.ResultsImmunocompetent mice that received a single S. pyogenes infection showed long-lasting immunity to subsequent IN infection, and no bacteria were detected in the lymph nodes or spleens. However, in the absence of IL-17, a single IN infection resulted in dissemination of S. pyogenes to the lymphoid organs, which was accentuated by repeated IN infections. In contrast to what was observed in the respiratory mucosa, skin immunity did not correlate with the systemic levels of IL-17. Instead, it was found to be associated with the activation of germinal center responses and accumulation of neutrophils in the spleen.DiscussionOur results demonstrated that IL-17 plays a critical role in preventing invasive disease following S. pyogenes infection of the respiratory tract.

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A Superficial Skin Scarification Method in Mice to Mimic Streptococcus pyogenes Skin Infection in Humans

Cited by 5 publications

References 9 publications

Pathogenesis, epidemiology and control of Group A Streptococcus infection

Pathogenesis, epidemiology and control of Group A Streptococcus infection

A Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils

Disruption of IL-17-mediated immunosurveillance in the respiratory mucosa results in invasive Streptococcus pyogenes infection

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