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Monoclonal Antibodies against 2019-New Coronavirus

Periodic Reporting for period 3 - MANCO (Monoclonal Antibodies against 2019-New Coronavirus)

Reporting period: 2022-09-01 to 2023-05-31

In response to the coronavirus disease 2019 (COVID-19) pandemic, also referred to as SARS-COV-2, tremendous efforts have been made to pull research initiatives together in order to accelerate the coordinated response against this coronavirus outbreak. MANCO is one of the 18 projects that was successfully selected by the European Commission, which is devoted to the development of Monoclonal Antibodies against the corona virus SARS2/COVID-19 for clinical use. At the last stage of the project another objective was added which was to test the efficacy and safety of an anti-SARS-COV-2 antibody produced by the C1 fungal production platform and compare this to the same antibody produced in mammalian cells.
With some delay a number of monoclonal antibodies were generated successfully that blocked the infection of human cells by SARS2. Two of these were characterized extensively but had to be replaced as the preferred antibody for further development, because they were not effective in blocking the UK and South Africa variants of the virus that appeared later. New immunisations were therefore carried out resulting in an antibody 87G7 that blocked all variants including Omicron BA.1 and BA.2 Both mouse and hamster infection models were established and the antibody was tested successfully in these animal models. Due to the delay a change of the project was proposed because the antibody strategies were overtaken by the development of anti-Covid 19 vaccines. After approval by the EU and the Manco scientific advisory board it was decided to test out a new production platform for monoclonal antibodies that is faster and much cheaper which if successful would put antibody therapeutics with reach of poor and low-income countries for all type of diseases that would benefit from an antibody therapy. The project was therefore successfully changed to a novel fungal production platform, called C1 that was developed by Dyadic. The lead candidate antibody 87G7 produced by the C1 platform was compared to the traditional mammalian cell produced 87G7 biochemically and structurally in vitro and prophylactically and therapeutically tested in 3 animal models in vivo, mice, hamsters and non-human primates (NHP) to go towards a clinical trial. These tests were successful and the C1 generated 87G7 antibody was shown to be completely safe and effective in all models including NHP. Thus, the production platform cuts production costs considerably. The regulatory and ethical aspects are in place and a communication strategy has been developed. However the lead candidate antibody 87G7 was not taken any further in development because yet novel variants of the omicron virus appeared which escape neutralization by the antibody and due to the successful development of vaccines there is no interest by pharmaceutical companies to develop antibodies for treatment. The C1 antibody results have been submitted for publication.
Current progress beyond the state of the art was the development of an antibody that blocks the infection of the important SARS2 variants and that could be used in combination with an existing antibody (47d11) to prevent the escape of novel viral variants. This project resulted in:
1. The development of a number of anti-Sars2 antibodies in response to the emerging variants of the virus that blocked such variants that had appeared.
2. The most powerful antibody developed was 87G7 that blocked all variants of concern including the first Omicron variants, but which does not neutralize the most recent Omicron variants BA4 and 5.
3. Several animal models to test the antibodies were developed i.e. transgenic mouse expressing the human receptor for SARS2, hamsters and non-human primates.
4. Most importantly a novel and much cheaper production platform (C1) has been tested using the lead antibody 87G7. The C1 produced antibody was tested successfully in hamster and non-human primate infection experiments both as a prophylactic and a therapeutic antibody.
5. The successful testing of the C1 produced antibody potentially has a large socio-economic impact, because the technology is transferable and opens the way to producing antibodies faster and at much lower cost putting it within reach of low- and middle-income countries not just for Covid but also for other therapeutic applications such as cancer immunotherapy.
6. The process of obtaining regulatory approval has been started.