Introduction

Strep A causes more than 700M infections globally and is a top ten cause of death worldwide. No vaccine exists, so antibiotics are essential for effective treatment. The WHO has made the development of Strep A vaccine a global priority.

Glycoconjugate vaccines, which are obtained by carbohydrates covalently bound to protein carriers, are among the most effective means of combating infections as they induce long-lasting (B- and T-cell) immunity. Historically difficult and expensive to create, the glycoconjugate vaccine development process has been revolutionised by the new, lower-cost, and customisable, bio-conjugation method. 

Challenge

RHAPSEDA’s vision is to create a research and development vaccine business in Scotland with global reach. Successful Proof-of-Concept for a Strep A vaccine production platform will pave the way for the development of other human and veterinary glycoconjugate vaccines.

The business opportunity relied on using a patented strain of E. coli, which would imply licensing costs for deployment in both high income countries and low to middle income countries, where it is badly needed. RHAPSEDA therefore wanted to investigate development of a proprietary alternative to the commercially available strain.

Solution

The objectives of the project were to clone, verify, and test an alternative production approach that would provide the freedom to operate and remove the need to access  proprietary bacterial strains. Plasmids were cloned, purified, and sequenced before transforming into E. coli bacteria for test expressions. A pilot screen was conducted to identify the production levels of the glycoconjugate in a small-scale batch s.

The project also allowed changes to the production process to reduce the number of antibiotic resistance cassettes incorporated into the E. coli cells. A revised system with less antibiotic resistance cassettes reduces the stress onto cells, streamlines the production by allowing more control in manufacturing. This is an important step forward in providing a sustainable production system giving the RHAPSEDA team the freedom to operate and produce these important vaccine candidates to guarantee affordable vaccines for all.

Outcome

The project was successful in developing alternative systems that reduce the antibiotics used in the platform technology and provide freedom to operate. This has a positive impact on the value of the system, due to increased consistency, reduced costs, and reduced use of contaminants (antibiotics) and will allow RHAPSEDA to advance their plans towards commercialisation.