The faces behind the CARE work-packages – WP6

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It is no surprise that it is designed in a comprehensive, yet agile, structure to fulfill the 37 partners’ shared key goals: (1) to identify therapeutics for the current pandemic, (2) to identify antiviral therapies for future outbreaks and (3) to increase the understanding of the pathophysiology of COVID-19. In a set-up of eight work-packages (WPs), the scientists and management at CARE carry out the project activities that have so far resulted in valuable learnings about COVID-19 and how it might be defeated 

In this monthly series, we go behind the scenes through brief interviews with the leadership of each of the eight CARE work-packages to hear insights on what makes their work so special, as well as their challenges and hopes.  

CARE Consortium Quote Cards WP6 Roger Le Grand
CARE Consortium Quote Cards WP6 Bagirath Gngadharan

WP6 – From lead to pre-clinical candidate and proof-of-concept in in vivo models 

The CARE work-package 6 (WP6) aims to to pre-clinically assess ADME, PK:PD, potency and safety of therapeutic candidates in vitro and in vivo models. Roger Le Grand (CEA) and Bagirath Gangadharan (Takeda) provided us in a short interview with insights into the activities of this work package, its highlights and the challenges that they had to overcome.

 How has the collaboration within your WP team developed over the past two years?   

Roger: The virus has challenged us with its frequent variations. To cope with this, we have expanded an already strong collaboration model with regular WP 6 meetings and dedicated project managers by adding trans-work package meetings, for instance with WP 4/7 for the antibody development, and with WP 3/7 for the small molecule development. And once we started testing a specific drug, we moved from more general data sharing to more specific interactions with one or two partners that are fully involved in this drug. An example is the work we did with the Lausanne group (CHUV) – because they brought an antibody into the pipeline to be tested in the non-human primate model. Another example is the early work with Dundee on the NSP14 series.

 

What has surprised you about working on the CARE project?

Roger: I think what we can consider unique in this consortium is the level of the contribution of the European Union to the large taskforce to find therapeutics for COVID-19 – this was put in place very quickly following the beginning of the pandemic. It is also amazing to see how quickly the diverse groups across academic and industry partners are managing to adapt processes and the amount of learnings is just enormous.

 

What makes the work for CARE special for you and your WP team?

Roger: I think what is different is the level of commitment of the different partners on a very focused purpose – taking into consideration that we have a large number of partners. In other collaborations very often people start focusing their efforts on their own interests very quickly and I think that CARE does a great job in keeping this focus on common interests. We have built a legacy with all the tools, the screening processes, the animal models, the methodology for the clinical trials being in place – in the future this will be very useful for other types of infections.

 

What highlights can you share from two years with your WP team so far?

Bagi: WP6 has developed multiple animal models to test the efficacy of lead compounds that are generated through CARE. This includes transgenic and humanized mouse models and a Syrian gold hamster model – these will be used for efficacy studies of our leading antiviral hit compounds, as derived from WP1-4. Additionally, also mouse-adapted SARS-CoV-2 strains will be used in the mouse model. A non-human primate model was developed for testing late-stage stage compounds, to look at both efficacy and pharmacokinetics. This is a big achievement, if you consider that we started from scratch with a new virus. There are several small molecules and mAbs that have been tested in the hamster model and we have tested mAbs in the non-human primate model, which contributed to the progression of the CHUV Ab to clinical trials (outside of CARE). This will all help to test other lead compounds to bring to clinical trials.

 

What are or were the biggest challenges within WP6? (and how did you overcome them?)

Bagi: What is difficult for us and WP6 is to permanently adapt the models to the new variants. You need to test the sensitivity of the animals to these new variants, to characterize the dynamics of its replication and the animal response – this is an ongoing process. Working in a consortium with great academic research partners working closely together as a team, we can share resources very fast between us and adapt our processes for drug testing by internal discussion very quickly.

The faces behind the CARE work-packages – WP5

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It is no surprise that it is designed in a comprehensive, yet agile, structure to fulfill the 37 partners’ shared key goals: (1) to identify therapeutics for the current pandemic, (2) to identify antiviral therapies for future outbreaks and (3) to increase the understanding of the pathophysiology of COVID-19. In a set-up of eight work-packages (WPs), the scientists and management at CARE carry out the project activities that have so far resulted in valuable learnings about COVID-19 and how it might be defeated 

In this monthly series, we go behind the scenes through brief interviews with the leadership of each of the eight CARE work-packages to hear insights on what makes their work so special, as well as their challenges and hopes.  

WP5_QuoteCard_Levy
WP5_QuoteCard_Jacob

WP5 – System Biology 

The CARE work-package 5 (WP5) aims to decipher the physiopathology of COVID-19 through combination of complementary OMICS-based approaches, and longitudinal immunological and virological analysis of patient samples from COVID-19 cohorts. Yves Levy (Inserm-VRI) and Howard Jacob (AbbVie) provided us in a short interview with insights into the activities of this work package, its highlights and the challenges that they had to overcome.

What highlights can you share from two years with your WP team so far?   

Yves: The main highlight is the partnership. WP5 integrates complementary virologic, immunologic and OMIC-based approaches – including genomics, transcriptomics, proteomics, metabolomics and interactomics – as well as expertise in data integration. The teams are working together to foster the understanding of the physiopathology of COVID-19 by always exchanging on how results from one team can complement and support discovery of other teams. This WP also benefits from a strong collaboration between the public and private sectors.

 

What are or were the biggest challenges within your WP? (And how did you overcome them?)

Yves: After two years of intensive research, WP5 partners are generating a notable amount of results from complementary approaches. The biggest challenge is the integration of all of these data to capitalise on them and decipher the host-virus interaction, from the cell to the patient. This challenge was anticipated by including a partner with expertise in biological data integration and will certainly be overcome by the strong collaboration between the partners.

 

How has the collaboration within your WP team developed over the past two years?

Howard: Over the past two years, WP5 has gone from envisaged projects to project execution and results. Patient recruitment and experiments are well on their way to being completed and have already produced important results. COVID-19 cohorts have highlighted neutrophil activation as a hallmark of disease and identified CD177 as a prognostic marker.

CRISPR-Cas9 screens, fluxomics, phospho-proteomics, and transcriptomics experiments on both patient samples and in vitro models have yielded important insights into host genes and pathways involved in COVID response. Bioinformatics analysis has illuminated viral-host protein interactions and the mechanisms underlying genetically determined differences in viral infection and disease progression.  We are also making progress improving WP5 collaboration and data sharing.

 

What has surprised you about working on the CARE project?

Howard: I am pleasantly surprised by the significant progress we have made, the spirit of open collaboration, and efficient coordination of a very complex global endeavor.

 

What makes the work for CARE special for you and your WP team?

Howard: It is an exciting and rewarding opportunity to work with a global team of some of the worlds most talented scientists who all share a common goal of accelerating cures to one of the most severe health crises of our generation.

The faces behind the CARE work-packages – WP4

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It is no surprise that it is designed in a comprehensive, yet agile, structure to fulfill the 37 partners’ shared key goals: (1) to identify therapeutics for the current pandemic, (2) to identify antiviral therapies for future outbreaks and (3) to increase the understanding of the pathophysiology of COVID-19. In a set-up of eight work-packages (WPs), the scientists and management at CARE carry out the project activities that have so far resulted in valuable learnings about COVID-19 and how it might be defeated 

In this monthly series, we go behind the scenes through brief interviews with the leadership of each of the eight CARE work-packages to hear insights on what makes their work so special, as well as their challenges and hopes.  

WP4_QuoteCard_Veldman
WP4_QuoteCard_Magnay

WP4 – Generation and characterization of monoclonal antibodies against SARS-CoV-2 and related coronaviruses 

The CARE work-package 4 (WP4) focuses on the generation and characterization of monoclonal antibodies against SARS-CoV-2 and related coronavirus. Trudi Veldman (AbbVie) and Maureen Magnay (Takeda), who recently took over the EFPIA co-lead of WP4, elaborated in a short interview on what the new role means to them and the WP4 team.

Taking over the WP4 industry leadership, what accomplishments are you building on?   

Trudi: We have some great partners in WP4 who have been working in the virology field for many years, whether studying HIV or coronaviruses.  Assays are in place and the rapid access to structural information about the spike protein is a key asset. The knowledge and experience that our partners bring will be instrumental in our next phase as we build a strategy for the coming years.

Maureen: After almost two years of working together, the WP4 team has built a solid foundation, respect and understanding of each other’s expertise in addition to building a framework for team collaboration. Progressing to the next phase as part of CARE, we will leverage both this and the broad and deep experience that partners bring to the program.

 

What will change with your new role as part of the WP4 industry leadership?

Maureen: I look forward to continuing to work with WP4 members, co-leading with Trudi. Changes as co-leader will involve additional involvement in strategic discussions, updates and meetings and the wider CARE community.

 

What makes the work for CARE special for you and your WP team?

Maureen: The most interesting aspects of being part of CARE relate to the fact that we are an open scientific team regardless of affiliation, working towards a common highly topical goal; the output of which has potential to be incredibly beneficial to society. The open approach to the fast paced and fluctuating scientific knowledge on SARS-CoV-2 has been an entirely new way of working. It has been wonderful to work with WP4 team members, their breadth of knowledge, experience, commitment, team spirit and respect.

 

What have you personally learned so far through the experience of working in CARE?

Trudi: My greatest lesson is that the SARS-CoV-2 spike protein is a fast-moving target and it challenges us as it manages to escape our therapeutic antibodies whether they are designed in the laboratory or isolated from convalescent patients. The recent appearance of the Omicron variant showed that most of the potent clinical and approved antibodies became obsolete in a matter of weeks.  While the rate of SARS-CoV-2 mutations has been high, I am equally impressed with the speed with which the scientific community investigates and shares new data. This transparency is key to developing new strategies.

 

What aspects will you be focusing on in your new role as industry lead of WP4?

Trudi: It feels like a “reset button” has been pressed and we need to develop a strategy for CARE and WP4 that makes sense in the light of our current knowledge. The big question is whether we can identify epitopes on the spike protein that are conserved, not sensitive to antigenic shift and when targeted with an antibody would prevent infection.

 

How will the two of you work together sharing the WP4 industry leadership?

Trudi: We will likely divvy up some responsibilities as we settle into this role, but the main reason for doing this together is to have somebody to bounce ideas off while we figure out where to go next as a team.

Published in eBioMedicine: Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine

The CARE partner Centre Institut National De La Santé Et De La Recherche Médicale – Vaccine Reserch Institute (INSERM-VRI) published a paper reporting on the design and testing of a protein subunit vaccine CD40.CoV2. The immunogenicity and antiviral efficacy of the vaccine was demonstrated in preclinical testing, and shown to be unaffected by Variants of Concern (VOC) mutations: indicating potential for enriching the available vaccine portfolio by extending the breadth of immune responses against current and emerging VOCs.

To learn more, click here: Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine

Published in JAMA Oncology: Humoral Responses Against Variants of Concern by COVID-19 mRNA Vaccines in Immunocompromised Patients

The CARE partner Centre Hospitalier Universitaire Vaudois (CHUV) in collaboration with Lausanne University Hospital published a paper reporting on the durability of neutralizing antibody responses elicited by messenger RNA vaccines BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) against the SARS-CoV-2 variants of concern (VOCs) in immunocompromised patients and healthy controls. The study showed a loss of neutralizing antibody response against the circulating VOCs at 6 months after vaccination, the loss being demonstrably greater for immunocompromised patients.

To learn more, click here: Humoral Responses Against Variants of Concern by COVID-19 mRNA Vaccines in Immunocompromised Patients

The faces behind the CARE work-packages – WP6

22 September 2022
The faces behind the CARE work-packages - WP6 CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It is no surprise that it is designed in a comprehensive, yet agile, structure to fulfill the 37 partners’ shared key goals: (1) to identify therapeutics for the current pandemic, (2) to identify antiviral therapies for future outbreaks and (3) [...]