Schommers, Philipp - B 10

Despite significant advances in antiretroviral therapy, HIV/AIDS remains a persistent global health threat. HIV-1-reactive broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope protein (HIV-1env) have shown promise in suppressing viremia, delaying viral rebound and reducing the viral reservoir in humans. However, the extensive genetic diversity of HIV-1 and the ability of the virus to evade bNAbs pose challenges to the use of these antibodies as stand-alone therapies. Even combinations of the most potent bNAbs can lead to viral escape due to pre-existing resistance or rapid mutations. Therefore, we here aim to develop and test multispecific anti-HIV-1 antibodies that target multiple HIV-1env epitopes to enhance potency and overcome viral resistance.

Anti-HIV-1 multispecific antibodies (msAbs) have the potential to increase antiviral activity and limit viral escape, thereby addressing major clinical limitations of current anti-HIV-1 antibodies. We aim to identify a novel msAbs constructs that are superior to known antibodies, thereby supporting their future clinical development. Furthermore, we will advance our msAbs platform, which could also be used in the future to develop novel msAbs against e.g. oncological or rheumatological diseases.

• Implementation-focused evaluation of predefined multispecific antibody formats
  This project focuses on the practical evaluation of selected multispecific HIV-1 antibody constructs using established molecular and virological methods and will test different constructs for their ability to maintain the inteneded avidity of the included Fabs.
• Use of established in vitro assays for functional comparison
  Multispecific antibodies will be analyzed using well-established binding and neutralization assays to compare their antiviral activity with that of corresponding monospecific antibodies under standardized conditions.
• Candidate selection based on functional performance
  A small number of antibody constructs will be selected based on predefined performance criteria for further in vitro testing.
• Confirmatory in vivo testing in an established model system
  Selected antibody candidates will be tested in a validated humanized mouse model to confirm antiviral activity and assess viral suppression and rebound under controlled experimental conditions.

For more information, please check Schommers Lab. 

• Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
• Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
• German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany