CARE’s Young Researchers – Introducing Thijs Steijaert, PhD student, Leiden University Medical Centre

Meet Thijs! Thijs Steijaert is a PhD student at Leiden University Medical Centre and in this short video, describes for us his role in CARE Work Package 5, where his work is contributing to growing scientific knowledge of our understanding of host pathways involved in replication and pathogenesis of the SARS-CoV-2 virus using proteomics and phosphoproteomics. Take a look at this 50 second video to find out why this work, and the opportunity to take part in the CARE consortium, matters to Thijs.

CARE – Infographic: Work Package 2 Target-based drug discovery and design.

CARE has 8 Work Packages but do you know what each one does? Here, you can learn about the Work Package 2 team, their objectives, their partners, their breakthrough moments and more.

The infographic is also available here

Published in Viruses: Lower infectivity of recent SARS-CoV-2 omicron sub–variants in Syrian Hamster.

The CARE partner, KU Leuven (KUL) evaluated the infectivity of two important sub-variants of omicron in Syrian hamsters. Indeed, since the emergence of the first omicron SARS-CoV-2 variant at the end of 2021, several sub-variants have evolved and become predominant in the human population, showing enhanced transmissibility and ability to (partly) escape the adaptive immune response. These include EG.5.1, an XBB sub-variant, and BA.2.86, a phylogenetically distinct variant, which were compared to the BA.5 sub-variant, a preceding BA.2 descendant. The BA.2 variant was not chosen as a comparator as it does not replicate efficiently in the KUL hamster model as compared to the BA.5 sub-variant.

Both EG.5.1 and BA.2.86 sub-variants are attenuated in Syrian hamsters as compared to the BA.5 sub-variant, as shown by lower infectious titers in the lung and lower lung pathology scores, while the viral RNA loads in throat swabs were comparable in the 3 strains. Interestingly, no virus titers in the lungs of the hamsters infected with the BA.2.86 sub-variant were observed although high viral RNA loads were detected. Therefore, viral RNA loads in the throat swabs and the lungs as well as lung histopathology scores could be a more suitable readout for vaccine and antiviral studies involving these two new sub-variants.

The continuous emergence of sub-variants will remain a challenge as it may require updating vaccines and therapeutic antibodies. Pre-clinical models with the evolving sub-variants are therefore crucial not only to study the virological characteristics of these new sub-variants, but more importantly to evaluate the efficacy of updated and also novel vaccines as well as therapeutic options for which the efficacy is virus variant dependent such as neutralizing antibodies.

To learn more, click here: Comparing the Infectivity of Recent SARS-CoV-2 Omicron Sub-Variants in Syrian Hamsters

CARE’s Young Researchers – Introducing Wenjuan Du, Post-doctoral researcher, Utrecht University

Read about how Collins’s work in understanding how the coronavirus hijacks human host factors and processes has provided us with opportunities to develop therapies to inhibit viral replication.

CARE (Corona Accelerated R&D in Europe) is the largest European research initiative addressing the challenges of COVID-19. It comprises 38 partners, from both industry and academia, in a set-up of eight multidisciplinary work-packages (WPs). In this series, we highlight the work of some of the young researchers involved in CARE as part of their PhD or postdoctoral work. Here, we learn how this opportunity has benefited Wenjuan (Utrech University), while simultaneously benefiting CARE and its ambition to help society defeat COVID-19 and future pandemics.

What experience did you have working on a Public Private Partnership before joining CARE? 

Before joining CARE, I had limited experience working in Public Private Partnerships.

 

Why did you decide to get involved in CARE?

I completed my doctoral studies in June 2020, at a time SARS-CoV-2 had become a serious health problem worldwide. I was highly motivated to contribute to the fight against SARS-CoV-2 and saw CARE as an excellent network to join.

 

How did your involvement in CARE come about?

My involvement with CARE stemmed from my doctoral research within the Virology laboratory at Utrecht University. My experience with molecular virology, antibody expression and neutralization assays made me well suited for the antibody research endeavors within Work Package 4 of the CARE research program.

 

Tell us about the work you have been doing in the CARE consortium

Within the consortium, my responsibilities have been diverse. They included setting up assays monitoring SARS-CoV-2 variants and characterizing antibodies that were developed by our WP4 partners. We evaluated the neutralization potency and breath of SARS-CoV-2 antibodies by using a pseudovirus system. More recently we started to develop human monoclonal antibodies against the emerging porcine deltacoronavirus (PDCoV), to enhance pandemic preparedness against this virus which can infect humans. We identified several antibodies with virus neutralizing activity, one of which targets a conserved epitope that is shielded from antibody recognition by other domains in the natural spike conformation. This antibody exhibits broad reactivity against related deltacoronaviruses and shows potential for future therapeutic use. Our studies on these antibodies have also provided more insight in PDCoV Spike-mediated cell entry. These findings are soon to be published in Nature Communications.

 

What highlights can you share from your time in the CARE consortium so far?

Highlights from my time in the CARE consortium include identifying antibodies with broad neutralization activity, particularly those that target conserved epitopes. These results have given me a great sense of accomplishment.

 

Why does this work matter?

Our research has deepened our understanding of the humoral immune response to combat  coronaviruses and the potential for these RNA viruses to evade from it. Our efforts have underscored the potential of antibodies targeting conserved epitopes on the spike protein to serve as therapeutic agents against future emerging coronaviruses.

 

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

I have benefited by acquiring new experimental skills, strengthening critical thinking, and expanding my professional network. Additionally, CARE provided me the opportunity to work with a great team of scientists in Utrecht, as well as with other scientists from academic and private partners within WP4, which was a rewarding and enriching experience.

 

How have you benefited from your involvement in CARE?

I have benefited immensely by interacting with experienced industry and academia experts who are willing to mentor and guide the upcoming scientists within the consortium. I have been able to sharpen my technical as well as interpersonal skills since I joined the consortium.

Published in Viruses: CXCL12 and CXCL13 Cytokine Serum Levels Are Associated with the Magnitude and the Quality of SARS-CoV-2 Humoral Responses

The CARE member, Centre Hospitalier Universitaire Vaudois (CHUV), has published a paper on the differences observed between hospitalised and non-hospitalised patients following SARS-CoV-2 infection in terms of the levels of detectable anti-SARS-CoV-2 neutralising responses and antibodies titres, which were significantly lower in non-hospitalised donors.

The aim of this work was to identify early factors that could predict the severity of SARS-CoV-2 infection. To this end, plasma and peripheral blood mononuclear cells were collected at 6 months post-onset of symptoms from 72 patients with severe COVID-19 who required hospitalization (31 of whom were admitted to intensive care) and 23 individuals who did not require hospitalization.

Blood and serum samples collected at 6 months post-onset of symptoms were used to characterize the ex vivo cellular and serum immune signatures, using mass cytometry and multiplex bead assays, respectively. The overall results suggest that the balance between the cytokines CXCL12 and CXCL13 may be an early predictive marker associated with the magnitude and the quality of SARS-CoV-2 antibody and memory B cell responses.

This work may help to improve the care of infected patients through enabling a better understanding of the immunological markers associated with long-lasting immune responses to SARS-CoV-2.

To learn more, click here: CXCL12 and CXCL13 Cytokine Serum Levels Are Associated with the Magnitude and the Quality of SARS-CoV-2 Humoral Responses

CARE’s Young Researcher -Thijs Steijaert

20 June 2024
CARE’s Young Researchers – Introducing Thijs Steijaert, PhD student, Leiden University Medical Centre Meet Thijs! Thijs Steijaert is a PhD student at Leiden University Medical Centre and in this short video, describes for us his role in CARE Work Package 5, where his work is contributing to growing scientific knowledge of our understanding of host [...]