The immunology of a putative recombinant vaccine against Streptococcus pyogenes utilising hepatitis B virus-like particles as an antigen delivery platform

The immunology of a putative recombinant vaccine against Streptococcus pyogenes utilising hepatitis B virus-like particles as an antigen delivery platform

Rheumatic heart disease (RHD) is entirely preventable, yet it claims an estimated 300 000 lives annually. Rates of RHD in children living in remote Australian Aboriginal and Torres Strait Islander communities are among the highest in the world and continue to rise, despite numerous and varied efforts to reduce them. It is predicted that by 2031, 14 500 Australians will be living with the debilitating effects of RHD. The cost associated with the care of Australians with RHD, between 2016 and 2031, is estimated at AUD $ 317 million. RHD is a an autoimmune sequala of a superficial infection caused by the bacterium, Streptococcus pyogenes (Strep A) and the most effective way to prevent RHD is to prevent the antecedent infection. The consensus among researchers and medical professionals is that vaccination would be the most effective way to do this. Yet, despite decades of research, there is currently no vaccine available that would protect children from the more than 80 different strains of Strep A endemic in Australia. This thesis describes the design, development, characterisation and evaluation of a putative vaccine against Strep A utilising hepatitis B virus-like particles (VLP) as a platform to deliver the highly immunogenic Strep A epitope, p*17, to the host’s immune system. The recombinant chimeric VLPs, VLP-p*17, were expressed in a mammalian protein expression system and spontaneously formed nanoparticles with repetitive surface expression of p*17. BALB/c mice immunised with VLP-p*17, formulated with the commonly used adjuvant Alum, produced high titres (mean 3.7 x 104) of p*17-specific IgG after three 0.5 μg doses. When formulated with the more recently developed saponin-based adjuvant, Vet-SAP®, VLP-p*17 induced significantly higher titres (mean 7.7 x 104) of p*17-specific IgG after three 0.5 μg doses. HBsAg-S is the basis of several human vaccines with proven safety and efficacy, and large-scale manufacturing systems producing HBsAg-S VLPs are already well established. VLP-p*17, formulated with a saponin-based adjuvant has significant potential as a safe, efficacious and cost-effective vaccine against Strep A infections and associated non-infectious complications such as rheumatic heart disease.

File reproduced in accordance with the copyright policy of the publisher/author.