Understanding the immunological mechanisms underlying (protection from) severe virus-mediated respiratory disease is essential for the development and implementation of safe and effective vaccination strategies

Research projects

The research of Puck van Kasteren focuses on respiratory viral infections (RSV, SARS-CoV-2, and influenza) along two main lines of investigation:

1.    Fc-mediated antibody functionality

Immunological protection against viral infection is generally assessed based on antibody concentration and/or neutralization capacity. However, antibodies can also mediate activation of various (innate) immune cells and complement via their Fc-domain. This may contribute to protection or, alternatively, lead to a potentially harmful inflammatory response. We use antigen-specific bead-based assays and flow cytometry to investigate Fc-mediated antibody effector functions in various clinical (vaccination) studies. Insights into the mechanisms underlying antibody-mediated phagocytosis, cytotoxicity, and complement activation will contribute to our understanding of (vaccine-induced) antibody-mediated protection.  

2.    Virus-host interaction in the epithelium

The respiratory epithelium is the primary target tissue for respiratory viral infections such as RSV, SARS-CoV-2, and influenza. Initial cellular responses at the epithelium are important for immediate protection, the development of (severe) disease, and will likely influence the subsequent local and systemic immune response. Understanding the interplay between virus and host at the primary site of infection is therefore important for the design of safe and effective vaccines. In our projects, we aim to (further) develop in vitro primary differentiated human epithelial infection models that include immunological components. By mimicking the natural human epithelium as closely as possible we hope to increase the predictive value of preclinical vaccine assessment and reduce the need for animal studies. In support of this work, we make use of a state-of-the-art reverse genetics system for RSV based on TAR cloning in yeast.

Background

Puck van Kasteren obtained her PhD in Molecular Virology from Leiden University in 2014, where she studied the molecular mechanisms underlying immune evasion by a viral deubiquitinase and its possible use for the development of a live-attenuated vaccine. Since 2016, she is working as a virologist at the Center for Immunology of Infectious Diseases and Vaccines (IIV), focusing on the immunological mechanisms underlying protection from respiratory viral infections and disease. Her past and current work is funded by the Dutch Ministry of Health, Welfare and Sports (VWS), IMI2 (Inno4Vac, 2021-2026), ZonMW (Off Road grant, 2018-2019), and an EMBO short-term fellowship (2013). Puck van Kasteren is a board member of the Royal Dutch Society for Microbiology (KNVM) since 2020.   

Areas of expertise

• Virology
• respiratory viruses (RSV, SARS-CoV-2, influenza)
• antibody functionality
• vaccines
• reverse genetics

Team members

• Anke Lakerveld (PhD-student)
• Rosanne Koutstaal (PhD-student)
• Anne Gelderloos (research technician)
• Hendrik-Jan Hamstra (research technician)

Former team members

• Marion Hendriks (research technician)
• Elisabeth (Liz) van Erp (PhD-student, graduated 2019)
• Lie Mulder (research technician)

Key publications

• Yu, X., Lakerveld, A. J., Imholz, S., Hendriks, M., Ten Brink, S., Mulder, H. L., de Haan, K., Schepp, R. M., Luytjes, W., de Jong, M. D., van Beek, J., & van Kasteren, P. B. (2020). Antibody and Local Cytokine Response to Respiratory Syncytial Virus Infection in Community-Dwelling Older Adults. mSphere, 5(5), e00577-20. 
• van Erp, E. A., Lakerveld, A. J., de Graaf, E., Larsen, M. D., Schepp, R. M., Hipgrave Ederveen, A. L., Ahout, I. M., de Haan, C. A., Wuhrer, M., Luytjes, W., Ferwerda, G., Vidarsson, G., & van Kasteren, P. B. (2020). Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation. Clinical & translational immunology, 9(2), e1112.
• van Kasteren, P. B., Bailey-Elkin, B. A., James, T. W., Ninaber, D. K., Beugeling, C., Khajehpour, M., Snijder, E. J., Mark, B. L., & Kikkert, M. (2013). Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells. Proceedings of the National Academy of Sciences of the United States of America, 110(9), E838–E847.