The Streptococcus pyogenes vaccine landscape

Walkinshaw, Donald R.; Wright, Meghan E. E.; Mullin, Anne E.; Excler, Jean Louis; Kim, Jerome H.; Steer, Andrew C.

doi:10.1038/s41541-023-00609-x

Cited by 44 publications

(48 citation statements)

References 44 publications

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“…pyogenes isolates could provide rich information on vaccine coverage in our communities. The vaccine candidates undergoing clinical trials, such as the 30-valent vaccine, are the most promising tools to reduce GAS infection numbers [69–71]. On this note, under the assumption that all subtype emm alleles of a parent emm- type were covered by the 30-valent vaccine candidate [72], approximately 83 % of our invasive isolates and 61 % of our non-invasive isolates were covered or had documented evidence of cross-reactivity [70, 72].…”

Section: Discussionmentioning

confidence: 99%

Insights gained from sequencing Australian non-invasive and invasive Streptococcus pyogenes isolates

Butler,

Story,

Green

et al. 2024

Microbial Genomics

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Epidemiological data have indicated that invasive infections caused by the Gram-positive cocci Streptococcus pyogenes (group A streptococcus, GAS) have increased in many Australian states over the past two decades. In July 2022, invasive GAS (iGAS) infections became nationally notifiable in Australia via public-health agencies. Surveillance for S. pyogenes infections has been sporadic within the state of New South Wales (NSW). This has led to a lack of genetic data on GAS strains in circulation, particularly for non-invasive infections, which are the leading cause of GAS’s burden on the Australian healthcare system. To address this gap, we used whole-genome sequencing to analyse the genomes of 318 S . pyogenes isolates collected within two geographical regions of NSW. Invasive isolates were collected in 2007–2017, whilst non-invasive isolates were collected in 2019–2021. We found that at least 66 different emm-types were associated with clinical disease within NSW. There was no evidence of any Australian-specific clones in circulation. The M1UK variant of the emm1 global pandemic clone (M1global) has been detected in our isolates from 2013 onwards. We detected antimicrobial-resistance genes (mainly tetM, ermA or ermB genes) in less than 10 % of our 318 isolates, which were more commonly associated with non-invasive infections. Superantigen virulence gene carriage was reasonably proportionate between non-invasive and invasive infection isolates. Our study adds rich data on the genetic makeup of historical S. pyogenes infections within Australia. Ongoing surveillance of invasive and non-invasive GAS infections within NSW by whole-genome sequencing is warranted to inform on outbreaks, antimicrobial resistance and vaccine coverage.

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Section: Discussionmentioning

confidence: 99%

Insights gained from sequencing Australian non-invasive and invasive Streptococcus pyogenes isolates

Butler,

Story,

Green

et al. 2024

Microbial Genomics

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“…With the emerging recognition of the role of S. pyogenes pyoderma in the development of ARF and RHD, understanding whether low-burden detection of S. pyogenes in skin lesions may contribute to the immune priming implicated in RHD pathogenesis will be essential [8][9][10][34][35][36]. With restored global interest in the development of a vaccine against S. pyogenes and RHD [37], it is critical to have a robust understanding of the epidemiology and strain diversity of S. pyogenes infection. Molecular methods should be central in enhanced surveillance for S. pyogenes in high-burden settings to aid the design and assessment of future interventions against RHD.…”

Section: Discussionmentioning

confidence: 99%

Molecular methods enhance the detection of pyoderma-related Streptococcus pyogenes and emm-type distribution in children

Hall,

Armitage,

Senghore

et al. 2024

Preprint

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Background: Streptococcus pyogenes-related skin infections are increasingly implicated in the development of rheumatic heart disease (RHD) in lower-resourced settings, where they are often associated with scabies. The true prevalence of S. pyogenes-related pyoderma may be underestimated by bacterial culture. Methods: A multiplex qPCR for S. pyogenes, Staphylococcus aureus and Sarcoptes scabiei was applied to 250 pyoderma swabs from a cross-sectional study of children <5 years in The Gambia. Direct PCR-based emm-typing was used to supplement previous whole genome sequencing (WGS) of cultured isolates. Results: Pyoderma lesions with S. pyogenes increased from 51% (127/250) using culture to 80% (199/250) with qPCR. Compared to qPCR, the sensitivity of culture was 95.4% for S. pyogenes (95% CI 77.2-99.9) in samples with S. pyogenes alone (22/250, 9%), but 59.9% (95% CI 52.3-67.2) for samples with S. aureus co-infection (177/250, 71%). Direct PCR-based emm-typing was successful in 50% (46/92) of cases, identifying 27 emm-types, including six not identified by WGS (total 52 emm-types). Conclusions: Bacterial culture significantly underestimates the burden of S. pyogenes in pyoderma, particularly when co-infected with S. aureus. Molecular methods should be used to enhance the detection of S. pyogenes in surveillance studies and clinical trials of preventative measures in RHD-endemic settings.

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“…The FDA partially eased their restrictions in 2006 and have now lifted them entirely. 86 Introducing a vaccine that can protect against all GAS serotypes is challenging. Investigation of GAS whole genome demonstrated that GAS isolates have extensive genomic heterogenicity due to gene exchange and single nucleotide polymorphisms and subsequent protein sequence variations.…”

Section: Antimicrobial Susceptibilitymentioning

confidence: 99%

Invasive Streptococcus pyogenes: A Short Literature Review

Tanrıverdi Çaycı,

Altındiş

2023

J Pediatr Infect Dis

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Objective Streptococcus pyogenes also called Group A streptococci (GAS) is an important pathogen known since past years and infects millions of people around the world every year and can cause death. Although it often causes pharyngitis and skin infections, it can also spread to the bloodstream and cause invasive GAS (iGAS) infections. In this review, studies on the epidemiology of GAS and iGAS and vaccine studies were reviewed. Methods A comprehensive search of databases was conducted up to April 1, 2023 to related studies, in English using the following terms: S. pyogenes, GAS, invasive S. pyogenes infections, iGAS, S. pyogenes vaccine. The data extraction was conducted by two investigators using the same methodology. Results There has been an increase in iGAS infections in various countries in the last year and they have been followed closely. Although the reason for the increase in iGAS cases cannot be determined exactly, it is thought that the recent removal of coronavirus disease 2019 restrictions and the increase in the number of individuals susceptible to GAS and to viral respiratory pathogens is thought to have caused this situation. Another important issue with GAS is the vaccine studies. Vaccines are based on two different targets: M protein-based and non-M protein-based. Phase-I clinical trials have been initiated for some vaccines. Conclusion The increase in recent iGAS infections will draw attention to this agent and accelerate vaccine studies.

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The Streptococcus pyogenes vaccine landscape

Cited by 44 publications

References 44 publications

Insights gained from sequencing Australian non-invasive and invasive Streptococcus pyogenes isolates

Insights gained from sequencing Australian non-invasive and invasive Streptococcus pyogenes isolates

Molecular methods enhance the detection of pyoderma-related Streptococcus pyogenes and emm-type distribution in children

Invasive Streptococcus pyogenes: A Short Literature Review

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