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

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

doi:10.1038/s41598-021-83673-4

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.

Highlights

Pili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection
Streptococcus pyogenes, known as Group A Streptococcus (GAS), is a human pathogen that is estimated to cause over 500,000 deaths a nnually[1]
One-third of these deaths are caused by severe invasive infections, while the majority are attributed to rheumatic heart disease (RHD)

Summary

Introduction

Pili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection. The issue of antigenic variation of pilus proteins amongst different strains of GAS needs to be addressed. We demonstrate that immunisation with TeeVax[1] can generate opsonophagocytic antibodies and provides protective efficacy in a mouse model of GAS invasive disease.

Results

Conclusion