The consortium partnership strives to advance a new vaccine concept that confers highly cross-reactive protection against numerous SARS-CoV-2 variants of concern (VoCs) as well as other Betacoronaviruses (Link: CEPI Partners with Consortium of Bharat Biotech, University of Sydney and ExcellGene to Develop 'Variant-Proof' Covid-19 Vaccine). ExcellGene will produce complex chimeric Spike antigens using its engineered CHOExpress®-cell based technology. The Swiss company will use insights from several scientific and technical disciplines along with artificial intelligence to identify the most promising antigenic structure.

Novel vaccine designed for cross-reactive protection against SARS-CoV-2 Variants of Concern

ExcellGene is a recognized leader in the development and manufacturing of complex proteins (DNA to product) for therapeutic or prophylactic applications, an example being trimeric spike proteins of SARS-CoV-2 (1). Together with Bharat Biotech, and Prof. Jamie Triccas and his team at the University of Sydney, Australia, ExcellGene will generate and screen a large and diverse library of chimeric spike proteins to identify highly cross-reactive antigen structures that recall past and possibly future variants. CEPI will provide up to US$19.3 million in funding to develop a ‘variant-proof’ SARS-CoV-2 vaccine candidate for phase I clinical trials.

With this new funding, ExcellGene expands on a collaboration with the team of Prof. Jamie Triccas that started in early 2020. ExcellGene began to produce Wuhan trimeric SARS-CoV-2 spike proteins in March 2020, and subsequently Alpha, Beta, Delta and, recently, Omicron variants. The Company delivered these antigens to its partners as highly purified, stabilised, trimeric spike proteins that had been engineered for high-yield production. By April/May 2021, the Sydney group had verified that such trimeric adjuvanted spike preparations were highly immunogenic in preclinical models (2). Blocking virus infection was shown in-vitro and in preclinical models with virus variants different from the immunizing antigen. Earlier, ExcellGene had conducted research in an EU-Horizon 2020 funded project on an Ebola candidate antigen molecule that resulted in sterilizing immunity in pre-clinical challenge models (https://www.excellgene.com/2022/02/ebola-research-enables-sars-cov-2-trimeric-spike-proteins).

Finding and testing the ideal antigen: with AI mediation analysis and structure-function insights  

An entirely new “chimeric” spike antigen complex, different from any protein of existing SARS-CoV-2 variants, will be generated. It is expected that such a trimeric spike protein, composed of combined mutations that characterise virus variants of concern from 2020-2022 (VoCs), will induce a wider range of cross-reactivity against historic or future variants than any of the individual virus variants did before.

To do so, the ExcellGene team will produce complex chimeric proteins using its engineered CHOExpress®-cell based technology, and Prof. Triccas and his team will assess the range of immune responses in various animal species and undertake a Phase 1 trial to assess safety and immunogenicity of the lead candidate. Theoretically, a near infinite number of such chimeric molecules can be designed. ExcellGene will reduce the diversity of such structures through artificial intelligence mediation analysis in combination with structure-function insights gained in examining the evolution of spike versions that resulted in the emergence of VoCs. Variable immune responses in vaccinated people with different strains will also be taken into consideration. Thus, a more manageable number of putative antigens can be tested in ExcellGene’s high-throughput transient gene and stable pool CHO-based expression system for development and manufacturability.

A modern approach to developing vaccines for the world

Maria Wurm, Dr. es. sci., CEO of ExcellGene, thinks the Company’s technology shows the value of using a CHO-based technology platform to produce optimized antigens for vaccine production. “This new CEPI partnership is a great opportunity to showcase what is possible in the manufacturing of highly complex antigen structures, consisting of computer-designed individual monomers, for a potential variant-proof Covid-19 vaccine. We are excited to work closely with our consortium partners to reach this goal, and we hope it will contribute towards the science for this and other novel protein-based vaccines. Ultimately, we wish to contribute to solving major health care challenges, as most strikingly exposed by COVID-19, using technology and scale-up approaches that successfully provided tons of protein therapeutics made in cultivated animal cells in bioreactors.”

Prof Jamie Triccas, Sydney Institute for Infectious Diseases, The University of Sydney said: “We are delighted to partner with ExcellGene, Bharat Biotech and the CEPI organisation to progress our platform for the development of broadly protective COVID-19 vaccines. Our mission is to deliver safe, affordable and highly effective vaccines to combat existing and future SARS-CoV-2 variants, and our international consortium is well placed to achieve this goal. The University of Sydney will provide a framework for pre-clinical assessment of vaccine candidates, together with access to Australia’s world-class early phase clinical trial community.”

Dr. Krishna Ella, Chairman and Managing Director, BBIL said: “The global threat of SARS-CoV-2 is continuing with new infections over and over again, irrespective of prior infections or vaccinations. Thus, more applied research has to be done, both in laboratories like those of Prof. Triccas, and in a company like ExcellGene, that can provide entirely new antigen concepts that combine insights into SARS-CoV-2 gained over the last two and a half years. Being a successful vaccine producer, particularly in the COVID-19 field, does not allow us to rest. We are therefore very pleased in having convinced the CEPI organization that our partnership over three continents is a robust solution that promises to open a new door for a future cross-reactive vaccine.”