Periodic Reporting for period 2 - RapCo-19 (Rapid COVID-19 Passive Therapy Response Platform)
Reporting period: 2021-05-01 to 2022-05-31
The SARS-CoV-2 pandemic requires the most serious and rapid healthcare response seen in modern history. COVID-19 continues to be a global health problem over a year after the initial outbreak. The original scope of the project was to provide a fully validated process to use RemedyBio’s Nanoreactor platform to rapidly identify, produce and deliver antiviral neutralising antibodies to COVID-19. The need for a rapid therapeutic agent deployment is still evident over 18 months after the pandemic broke out. The challenges with vaccination, even in developed countries are enormous and the impact on emerging new strains is yet to be fully established. However, it is widely acknowledged that many countries are undergoing already a fourth wave. In addition, how long immunity lasts for following COVID-19 infection is a big unknown.
Short-lived passive immunisation with an anti-COVID-19 therapy is immediately required to treat infected patients and to ‘flatten the infection curve’ and to provide time for ‘herd immunity’ and mass vaccination approaches. Devising an effective strategy requires an approach that is designed to exploit the extreme heterogeneity of the human anti-viral immune response. RemedyBio’s Nanoreactor technology is such a system. It is the result of a 5-year research programme to develop a platform to rapidly and simultaneously analyse millions of single antibody-producing immune cells from an individual sample. In the context of COVID-19, this presents an opportunity to rapidly identify the best antibodies from the immune systems of COVID-19 convalescent patients from which to create a rapid passive therapeutic for those that are critically ill from the virus.
This project is designed to combine novel discovery and assay technologies to form a platform to rapidly identify, produce and deliver antiviral neutralising antibodies to COVID-19. Furthermore, it is expected that in the event of a future pandemic, Rapco-19 can be quickly adapted to deliver neutralising antibodies within 60 days once the process is fully developed and validated.
Short-lived passive immunisation with an anti-COVID-19 therapy is immediately required to treat infected patients and to ‘flatten the infection curve’ and to provide time for ‘herd immunity’ and mass vaccination approaches. Devising an effective strategy requires an approach that is designed to exploit the extreme heterogeneity of the human anti-viral immune response. RemedyBio’s Nanoreactor technology is such a system. It is the result of a 5-year research programme to develop a platform to rapidly and simultaneously analyse millions of single antibody-producing immune cells from an individual sample. In the context of COVID-19, this presents an opportunity to rapidly identify the best antibodies from the immune systems of COVID-19 convalescent patients from which to create a rapid passive therapeutic for those that are critically ill from the virus.
This project is designed to combine novel discovery and assay technologies to form a platform to rapidly identify, produce and deliver antiviral neutralising antibodies to COVID-19. Furthermore, it is expected that in the event of a future pandemic, Rapco-19 can be quickly adapted to deliver neutralising antibodies within 60 days once the process is fully developed and validated.
A major milestone of our RapCo-19 project is to functionally identify virus neutralising antibodies directly from primary B cells obtained from patients that have been infected with SARS-CoV-2 using the RemedyBio Nanoreactor platform. This milestone was achieved following optimisation and validation of the DiCAST Nanoreactor process for mass single-cell analysis of patient-derived B cells to identify SARS-CoV-2 neutralising antibodies. RemedyBio has incorporated antibody detection, affinity ranking and neutralisation within a single 24h screening process. Such approach allows the screening of millions B cells to select the best potential candidates on the basis of specificity and potency. Furthermore, the process of neutralisation was incorporated into the screening process, as opposed to the usual approach adopted by competitor technologies where neutralisation capacity needs to be tested downstream with lengthy (days & weeks vs hours in Nanoreactor) and labour intensive procedures (10,000 microtitre plates vs 1 array in Nanoreactor).
We have demonstrated within Deliverable 4.1 that the Rapco platform is not only capable of selecting neutralising antibodies, but that it is capable of screening against multiple variants of interest and different therapeutic modalities (Nanobodies and scFv libraries). Increasing the repertoire of potential candidates for downstream transfer for manufacture and ultimately rapid clinical deployment.
While we await the possible emergence of dangerous new variants beyond omicron, the immediate current relevance of new mABs against potential variants of concern is uncertain. Nonetheless, the need for a rapid therapeutic pandemic response platform, with capability to adapt to rapidly emerging new strains is highly valuable. The platform has been validated for identification and recovery of SARS-CoV-2 neutralising antibodies. We maintain a high level of readiness for pandemic response and applicability for Antibody discovery and B cell screening for other applications.
For instance, we have also addressed the screening of T cells with the platform, giving their potential in long-term immunological memory response that develops following patient recovery from COVID-19
Crucially, the data obtained to date validates RemedyBio Nanoreactor platform for the rapid discovery of patient-derived human monoclonal antibodies for any future pandemic rapid response.
We have demonstrated within Deliverable 4.1 that the Rapco platform is not only capable of selecting neutralising antibodies, but that it is capable of screening against multiple variants of interest and different therapeutic modalities (Nanobodies and scFv libraries). Increasing the repertoire of potential candidates for downstream transfer for manufacture and ultimately rapid clinical deployment.
While we await the possible emergence of dangerous new variants beyond omicron, the immediate current relevance of new mABs against potential variants of concern is uncertain. Nonetheless, the need for a rapid therapeutic pandemic response platform, with capability to adapt to rapidly emerging new strains is highly valuable. The platform has been validated for identification and recovery of SARS-CoV-2 neutralising antibodies. We maintain a high level of readiness for pandemic response and applicability for Antibody discovery and B cell screening for other applications.
For instance, we have also addressed the screening of T cells with the platform, giving their potential in long-term immunological memory response that develops following patient recovery from COVID-19
Crucially, the data obtained to date validates RemedyBio Nanoreactor platform for the rapid discovery of patient-derived human monoclonal antibodies for any future pandemic rapid response.
RemedyBio’s Nanoreactor process has been validated for mass single-cell analysis of patient-derived B cells to identify SARS-CoV-2 neutralising antibodies. RemedyBio has incorporated antibody detection, affinity ranking and neutralisation within a single 24h screening process. Such approach allows the screening of millions B cells to select the best potential candidates on the basis of specificity and potency. Furthermore, the process of neutralisation was incorporated into the screening process, as opposed to the usual approach adopted by competitor technologies where neutralisation capacity needs to be tested downstream with lengthy (days & weeks vs hours in Nanoreactor) and labour intensive procedures (10,000 microtitre plates vs 1 array in Nanoreactor). The optimised and validated approach presented in this report is of great significance and showcases the unique features of the RapCo19 platform in terms of speed, robustness and functional antibody information content. The validated platform has shown that it can preselect >1500 RBD binders from 1 patient and narrow this down to 122 candidates with predefined selected features such as ACE2 neutralisation. This makes cloning and expansion of the selected candidates more manageable and affordable for a speedy clinical evaluation and field therapy deployment.
Future steps include expression and in depth characterisation of lead antibody candidates (epitope discovery, binding affinities and mechanism of action). Purified antibody will be subsequently evaluated for clinical development.
Future steps include expression and in depth characterisation of lead antibody candidates (epitope discovery, binding affinities and mechanism of action). Purified antibody will be subsequently evaluated for clinical development.