In silico analysis of T-cell immunogenicity of seven pertussis proteins
The public private partnership established between the Intravacc Institute and the US-based company EpiVax is leading the design of a new vaccine against Bordetella pertussis, the causative agent of whooping cough. This project aims at identifying sequences from seven pertussis proteins that negatively impact the effectiveness of pertussis vaccines. Once identified with EpiVax’s state-of-the-art in silico vaccine design platform, these sequences can be re-engineered to remove troublesome combinations of amino acids. In parallel, ideal vaccine candidates are identified from these pertussis proteins. Intravacc will integrate these findings into the generation of a new vaccine.
With around 24 million people affected and over 160,000 deaths yearly, whooping cough remains a major health concern despite vaccination efforts. Current pertussis vaccines are effective in the short-term, but do not confer long-term immunity. New generations of vaccines are needed to address these shortcomings and to decrease pertussis incidence. Such vaccines will reduce costs and burden of extra boosters and maternal vaccination.
In silico tools can dramatically accelerate the design of vaccines by focusing candidate selection on high-value targets. Additionally, prospectively identifying and removing potentially immuno-suppressive sequences can help minimize adverse events caused by vaccines and improve their efficacy. The approach taken by this partnership also contributes to the Replacement, Reduction, Refinement principles for more ethical use of animals in testing.
A total of 19 potentially immuno-suppressive sequences were identified in seven proteins under study and four sequences were selected for re-engineering. Mutations were introduced to render these sequences less visible to the human and mouse immune systems and remove their suppressive properties. The effect of these mutations was validated using in vitro assays. Four sequences derived from pertussis toxin were found to be ideal vaccine candidates. These sequences, along with the engineered mutations, will be integrated into a new pertussis vaccine developed by Intravacc.
