A multivalent T-antigen-based vaccine for Group A Streptococcus

Loh, Jacelyn M. S.; Rivera-Hernandez, Tania; McGregor, Reuben; Khemlani, Adrina Hema J.; Tay, Mei Lin; Cork, Amanda J.; Raynes, Jeremy M; Moreland, Nicole J.; Walker, Mark J.; Proft, Thomas

doi:10.1038/s41598-021-83673-4

Cited by 22 publications

(22 citation statements)

References 51 publications

(53 reference statements)

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“…It clearly demonstrates the possibility of developing GAS vaccine that is broadly protective by targeting pili. 30 GAS is an iron-deficient bacterium which primarily relies on heme-iron to meet its requirements and survival in the host is dependent on the proteins which is involved in heme capture and heme import. Native human monoclonal antibody TRL186, helps mice survival in therapeutic and prophylactic mouse models after the intraperitoneal challenge with GAS strain (invasive).…”

Section: Vaccine Strategiesmentioning

confidence: 99%

Streptococcal Pharyngitis and Rheumatic Fever

Sujhithra¹,

Jayanthi²,

Chokkalingam³

et al. 2022

J. Pure Appl. Microbiol.

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Streptococcus pyogenes (Group A Streptococcus) causes a variety of diseases, from benign self-limiting infections of the skin or throat to lethal infections of soft tissue accompanied by multi-organ failure. GAS is one of significant species among Gram-positive pathogens which is responsible for several suppurative infections and non-suppurative sequelae. They also cause pharyngitis, streptococcal toxic shock syndrome (STSS), necrotizing fasciitis and other diseases. Currently, global burden of RF / RHD is undervalued. In 2010, RF and RHD were estimated as 15.6 million cases and deaths around 200,000 annually. Laboratory diagnosis includes cultural techniques, serology, PYR test, Bacitracin susceptibility test and antibiotic resistance testing helps in differentiating the Streptococcus pyogenes from other groups of Streptococci. Most of the Acute Rheumatic Fever cases gets missed or does not present in the initial stage rather it has been developed into advanced Rheumatic Heart Disease condition. Modified Jones criteria in 2015 will be helpful especially to the low risk population as it is challenging because of limited access to primary health care, diagnosis of streptococcal disease. In addition to this revised criteria, diagnosis still relies on clinical diagnostic algorithm. Vaccines based on M protein and T antigens are continuing to evolve with different results. Ongoing vaccine development is still challenging for the GAS research community, it will make a positive and lasting impact on the peoples globally.

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Section: Vaccine Strategiesmentioning

confidence: 99%

Streptococcal Pharyngitis and Rheumatic Fever

Sujhithra¹,

Jayanthi²,

Chokkalingam³

et al. 2022

J. Pure Appl. Microbiol.

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“…Loh et al [42] generated a multivalent vaccine called TeeVax1, a recombinant protein that consists of a fusion of six T-antigen domains. Vaccination with TeeVax1 produces opsonophagocytic antibodies in rabbits and confers protective efficacy in mice against invasive disease.…”

Section: Structure-based Vaccines Against Lyme Diseasementioning

confidence: 99%

Progress in the Development of Structure-Based Vaccines

Thomas

Abraham

2021

Vaccine Design

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The immune response elicited by vaccines against microorganisms makes it the most successful medical interventions against infectious diseases. Conventional vaccines have limitations in inducing immunity against many types of pathogenic microorganism. The genetic diversity of microorganisms, coupled with the high degree of sequence variability in antigenic proteins, presents a challenge to developing broadly effective conventional vaccines. Atomic-resolution structure determination is crucial for understanding antigenic protein function. Cryo-electron microscopy, nuclear magnetic resonance spectroscopy coupled with bioinformatics provide three-dimensional structure of the antigenic proteins and provide a wealth of information about the organization of individual atoms and their chemical makeup. The atomic detail information of proteins offers enormous potential to rationally engineer proteins to enhance their properties and act as effective immunogens to induce immunity. The observation that whole protein antigens are not necessarily essential for inducing immunity has led to the emergence "structural vaccinology." Structure-based vaccines are designed on the rationale that protective epitopes should be sufficient to induce immune responses and provide protection against pathogens. In 2013 we published a review on structure-based vaccines (Thomas and Luxon. Expert Rev Vaccines 12 1301-11, 2013). This review states the progress in development of structure-based vaccines since the first review.

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“…As surface‐exposed molecules, BP (also known as the T‐antigen) and AP1 have long been known to stimulate strong antibody responses in humans and animals 15,16 . The pilus is therefore considered as a potential vaccine target, 17‐21 and more recently, as a vaccine carrier 22,23 …”

Section: Introductionmentioning

confidence: 99%

“…14 As surfaceexposed molecules, BP (also known as the T-antigen) and AP1 have long been known to stimulate strong antibody responses in humans and animals. 15,16 The pilus is therefore considered as a potential vaccine target, [17][18][19][20][21] and more recently, as a vaccine carrier. 22,23 Immunization of mice and rabbits with multivalent recombinant T-antigen proteins induces specific and cross-reactive anti-T antibodies with bactericidal properties.…”

Section: Introductionmentioning

confidence: 99%

“…22,23 Immunization of mice and rabbits with multivalent recombinant T-antigen proteins induces specific and cross-reactive anti-T antibodies with bactericidal properties. 18 Similarly, administration of pili expressed on the nonpathogenic bacterium Lactococcus lactis stimulated the production of functional antibodies that possessed the ability to facilitate opsonophagocytosis and interfere with adhesion of GAS to keratinocyte cell lines. 17 Furthermore, when the pilus was utilized as a peptide carrier in a recombinant L. lactis-based mucosal vaccine platform, high levels of antibodies specific to the antigen were generated.…”

Section: Introductionmentioning

confidence: 99%

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Pilus proteins from Streptococcus pyogenes stimulate innate immune responses through Toll‐like receptor 2

et al. 2022

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The group A Streptococcus (GAS) pilus is a long, flexible, hair‐like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS virulence, the pilus has become an attractive target for vaccine development. While current research mainly focuses on pilus function and its potential as a vaccine component, there is a lack of knowledge on how the host immune system recognizes and responds to this abundant surface structure. Here we show that both assembled GAS pili and individual pilus proteins induce a potent release of the proinflammatory cytokines tumor necrosis factor and interleukin‐8. We further show that the surface‐exposed backbone pilin and ancillary pilin 1 subunits are Toll‐like receptor 2 (TLR2) agonists. Using reporter cell lines coexpressing human TLR2 in combination with either TLR1 or TLR6, we determined that activation was mediated by the TLR2/TLR6 heterodimer. Finally, we used solid‐phase and flow cytometry binding assays to illustrate a direct interaction between the pilus subunits and TLR2. These results provide further support for the suitability of the pilus as a vaccine component and opens potential avenues for using GAS pili as an adjuvant or immune‐modulation agent.

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A multivalent T-antigen-based vaccine for Group A Streptococcus

Cited by 22 publications

References 51 publications

Streptococcal Pharyngitis and Rheumatic Fever

Streptococcal Pharyngitis and Rheumatic Fever

Progress in the Development of Structure-Based Vaccines

Pilus proteins from Streptococcus pyogenes stimulate innate immune responses through Toll‐like receptor 2

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