Zehner, Matthias - CAP 41

The lack of effective and well-tolerated antiviral options, together with the absence of a vaccine, makes HCMV a persistent clinical burden, particularly in transplant medicine and congenital infection. Our work directly addresses these unmet needs by developing next-generation monoclonal antibodies with improved neutralization potency and targeting key viral proteins. Small-fragment antibodies further broaden the therapeutic potential by potentially blocking cell-associated spread, a major obstacle in treating HCMV infections. In parallel, our analysis of protective antibody responses provides key insights to guide rational vaccine design aimed at inducing long-lasting immunity. Strong collaborations with clinical partners enable preclinical testing and potential translation into clinical application, contributing to sustainable therapeutic and prophylactic solutions for vulnerable patient populations.

Our overarching goal is to translate mechanistic insights into innovative antibody-based therapies against HCMV. Specifically, we aim to:

1. Decode the HCMV-specific B cell response by high-throughput single-cell analysis of large donor cohorts, including rare individuals with broad and potent neutralizing activity.
2. Elucidate key molecular mechanisms of HCMV infection and immune evasion, focusing on viral entry, membrane fusion, cell-to-cell spread, and escape from antibody-mediated control.
3. Design and evaluate next-generation antibody formats, including bispecific antibodies and small-fragment antibodies, optimized not only for potent neutralization but also for engaging Fc-mediated effector functions like ADCC and phagocytosis.

By integrating these approaches, we aim to advance the understanding of protective immunity, support vaccine development, and deliver novel approaches for immunotherapies for HCMV.

Our research program aims to expand HCMV research in Cologne and establish a sustainable platform for antibody-based immunotherapies targeting HCMV, with broader applicability to other complex viral infections. Through advanced antibody engineering and mechanistic insight, we seek to overcome current therapeutic limitations and develop innovative treatment and prevention strategies for immunocompromised and high-risk patients. By identifying novel antibody targets and immune mechanisms, our work will also inform vaccine design and antiviral strategies. Close collaboration with clinical and industrial partners ensures the translation of findings into preclinical and clinical applications. As part of national and international research networks, we contribute to scientific exchange and long-term impact. Ultimately, we aim to improve patient care and establish a leading research program in antiviral antibody therapy.