Abstract
Since December 2019 the emergence of severe acute respiratory infections (COVID-19) caused by the new coronavirus SARS-CoV-2 in China has posed a huge threat to global health, with rapid infection of more than 45,000 people and over 1000 deaths by February 11, 2020. Currently there is no effective treatment or vaccine available for CoV infections in humans, largely due to the diversity of CoV family in wildlife and periodic zoonotic transmission from animal hosts to humans. The aim of this proposal is to develop a group of ‘universal’ therapeutic antibodies, called coronavirus broadly neutralizing monoclonal antibodies (CoV-bnMABs), capable of treating and protecting against different members of
the CoV family including the current outbreak of SARS-CoV-2. We intend to bring CoVbnMABs into clinical trial within a period of 12 months by characterization of their specificity to the SARS-CoV-2 as well as protective efficacy and safety in animal models. The outcome of this study would address an immediate unmet medical need and could provide effective tools against emerging pandemic CoV of the future.
the CoV family including the current outbreak of SARS-CoV-2. We intend to bring CoVbnMABs into clinical trial within a period of 12 months by characterization of their specificity to the SARS-CoV-2 as well as protective efficacy and safety in animal models. The outcome of this study would address an immediate unmet medical need and could provide effective tools against emerging pandemic CoV of the future.
Technical Summary
This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project.
Recently we have investigated antibody cross-reactivity between SARS-CoV and MERSCoV using a cohort (n=128) of SARS convalescent samples (serum and PBMC) collected during the 2003 outbreak in China. We isolated:
• A panel of human mAbs (hmAbs) (n=12) specific to the cross-reactive epitopes
between SARS-CoV and MERS-CoV by yeast-surface-display technology from PBMCs of SARS patients
• Four of 12 hmAbs showing stronger neutralizing activities against both SARS- and MERS-CoVs in pseudotype or wild-type virus assays , namely the CoV broadly neutralizing mAbs (CoV-bnMABs).
Because a new highly pathogenic coronavirus (2019-nCoV renamed as SARS-CoV-2 by WHO on 11th Feb) outbreak occurred in December 2019 in China, we compared CoV sequences and alignments and found that the S protein (the major target of antibody response) of 2019-nCoV shares higher homology with SARS-CoV (77 %) as compared with MERS-CoV (35%). Thus, we hypothesize that some of CoV-bnMABs generated from SARS patients will cross react with SARS-CoV-2 in addition to MERS-CoV and SARSCoV. Indeed, our preliminary data (obtained on 9th Feb 2020) have shown that the CoVbnMABs can specifically bind to SARS-CoV-2 S protein expressed on the surface of 293T cells . Therefore, we propose here to further characterize the CoV-bnMABs in terms of protective efficacy against SARS-CoV-2 while scaling up antibody production for IND-enabling CoVbnMAB CMC development, aiming to rapidly develop therapeutic antibodies for the current outbreak. Technically, in collaboration with a team of experts from UK and China, we will accomplish essential pre-clinical studies within 12 months and prepare for clinical trials.
Recently we have investigated antibody cross-reactivity between SARS-CoV and MERSCoV using a cohort (n=128) of SARS convalescent samples (serum and PBMC) collected during the 2003 outbreak in China. We isolated:
• A panel of human mAbs (hmAbs) (n=12) specific to the cross-reactive epitopes
between SARS-CoV and MERS-CoV by yeast-surface-display technology from PBMCs of SARS patients
• Four of 12 hmAbs showing stronger neutralizing activities against both SARS- and MERS-CoVs in pseudotype or wild-type virus assays , namely the CoV broadly neutralizing mAbs (CoV-bnMABs).
Because a new highly pathogenic coronavirus (2019-nCoV renamed as SARS-CoV-2 by WHO on 11th Feb) outbreak occurred in December 2019 in China, we compared CoV sequences and alignments and found that the S protein (the major target of antibody response) of 2019-nCoV shares higher homology with SARS-CoV (77 %) as compared with MERS-CoV (35%). Thus, we hypothesize that some of CoV-bnMABs generated from SARS patients will cross react with SARS-CoV-2 in addition to MERS-CoV and SARSCoV. Indeed, our preliminary data (obtained on 9th Feb 2020) have shown that the CoVbnMABs can specifically bind to SARS-CoV-2 S protein expressed on the surface of 293T cells . Therefore, we propose here to further characterize the CoV-bnMABs in terms of protective efficacy against SARS-CoV-2 while scaling up antibody production for IND-enabling CoVbnMAB CMC development, aiming to rapidly develop therapeutic antibodies for the current outbreak. Technically, in collaboration with a team of experts from UK and China, we will accomplish essential pre-clinical studies within 12 months and prepare for clinical trials.
