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

Abstract Pili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection. The major protein component of the GAS pilus is the T-antigen, which multimerises to form the pilus shaft. There are currently no licenced vaccines against...

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Main Authors: Jacelyn M. S. Loh, Tania Rivera-Hernandez, Reuben McGregor, Adrina Hema J. Khemlani, Mei Lin Tay, Amanda J. Cork, Jeremy M. Raynes, Nicole J. Moreland, Mark J. Walker, Thomas Proft
Format: Article
Language:English
Published: Nature Portfolio 2021-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-83673-4
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author Jacelyn M. S. Loh
Tania Rivera-Hernandez
Reuben McGregor
Adrina Hema J. Khemlani
Mei Lin Tay
Amanda J. Cork
Jeremy M. Raynes
Nicole J. Moreland
Mark J. Walker
Thomas Proft
author_facet Jacelyn M. S. Loh
Tania Rivera-Hernandez
Reuben McGregor
Adrina Hema J. Khemlani
Mei Lin Tay
Amanda J. Cork
Jeremy M. Raynes
Nicole J. Moreland
Mark J. Walker
Thomas Proft
author_sort Jacelyn M. S. Loh
collection DOAJ
description Abstract Pili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection. The major protein component of the GAS pilus is the T-antigen, which multimerises to form the pilus shaft. There are currently no licenced vaccines against GAS infections and the T-antigen represents an attractive target for vaccination. We have 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. Two further recombinant proteins, TeeVax2 and TeeVax3 were constructed to cover 12 additional T-antigens. Combining TeeVax1–3 produced a robust antibody response in rabbits that was cross-reactive to a full panel of 21 T-antigens, expected to provide over 95% vaccine coverage. These results demonstrate the potential for a T-antigen-based vaccine to prevent GAS infections.
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spelling doaj.art-e5c26595d82b49ec87d8e1591a0db6732022-12-21T20:29:27ZengNature PortfolioScientific Reports2045-23222021-02-0111111010.1038/s41598-021-83673-4A multivalent T-antigen-based vaccine for Group A StreptococcusJacelyn M. S. Loh0Tania Rivera-Hernandez1Reuben McGregor2Adrina Hema J. Khemlani3Mei Lin Tay4Amanda J. Cork5Jeremy M. Raynes6Nicole J. Moreland7Mark J. Walker8Thomas Proft9Department of Molecular Medicine & Pathology, School of Medical Sciences, The University of AucklandAustralian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of QueenslandDepartment of Molecular Medicine & Pathology, School of Medical Sciences, The University of AucklandDepartment of Molecular Medicine & Pathology, School of Medical Sciences, The University of AucklandDepartment of Molecular Medicine & Pathology, School of Medical Sciences, The University of AucklandAustralian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of QueenslandDepartment of Molecular Medicine & Pathology, School of Medical Sciences, The University of AucklandDepartment of Molecular Medicine & Pathology, School of Medical Sciences, The University of AucklandAustralian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of QueenslandDepartment of Molecular Medicine & Pathology, School of Medical Sciences, The University of AucklandAbstract Pili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection. The major protein component of the GAS pilus is the T-antigen, which multimerises to form the pilus shaft. There are currently no licenced vaccines against GAS infections and the T-antigen represents an attractive target for vaccination. We have 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. Two further recombinant proteins, TeeVax2 and TeeVax3 were constructed to cover 12 additional T-antigens. Combining TeeVax1–3 produced a robust antibody response in rabbits that was cross-reactive to a full panel of 21 T-antigens, expected to provide over 95% vaccine coverage. These results demonstrate the potential for a T-antigen-based vaccine to prevent GAS infections.https://doi.org/10.1038/s41598-021-83673-4
spellingShingle Jacelyn M. S. Loh
Tania Rivera-Hernandez
Reuben McGregor
Adrina Hema J. Khemlani
Mei Lin Tay
Amanda J. Cork
Jeremy M. Raynes
Nicole J. Moreland
Mark J. Walker
Thomas Proft
A multivalent T-antigen-based vaccine for Group A Streptococcus
Scientific Reports
title A multivalent T-antigen-based vaccine for Group A Streptococcus
title_full A multivalent T-antigen-based vaccine for Group A Streptococcus
title_fullStr A multivalent T-antigen-based vaccine for Group A Streptococcus
title_full_unstemmed A multivalent T-antigen-based vaccine for Group A Streptococcus
title_short A multivalent T-antigen-based vaccine for Group A Streptococcus
title_sort multivalent t antigen based vaccine for group a streptococcus
url https://doi.org/10.1038/s41598-021-83673-4
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