Vir Biotech research highlights mechanism to enhance monoclonal antibodies for inducing protective response

Vir Biotechnology announced the publication of preclinical research in an influenza animal model highlighting a new mechanism for enhancing the efficacy of monoclonal antibodies to treat viral infection and induce a protective response. Data demonstrate that selective engagement of an activating Fc receptor on dendritic cells by antiviral monoclonal antibodies induced protective CD8⁺ T cell adaptive responses. The paper, entitled “Fc-optimised antibodies elicit CD8 immunity to viral respiratory infection,” was published in the October 8, 2020, online edition of Nature.

“In the past several years, we’ve gained a better understanding of how integral Fc mediated effector functions of monoclonal antibodies are for their therapeutic efficacy in pre-clinical models of neoplastic, infectious and inflammatory diseases,” said Jeffrey V Ravetch, study senior author and Theresa and Eugene M Lang Professor and Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The Rockefeller University.

He said, “These approaches have been successfully applied to anti-tumour therapeutics and have resulted in improved clinical outcomes in a variety of oncologic diseases. Our present studies have uncovered a significant new mechanism by which antibodies, through their Fc region, can not only engage innate immune responses but activate adaptive T cell responses, thereby stimulating protective anti-viral immunity in these models.”

The research published in Nature focuses on the role of the Fc domain of monoclonal antibodies, regions with the capacity to bind to other immune cells through a family of receptors (the Fc receptors). By engineering antibodies with modified Fc domains to enhance binding to specific Fc receptors on innate immune cells, investigators observed an enhanced protective immune response. Certain modifications (GAALIE variants) were associated with activation of dendritic cells, as well as antiviral effector T-cells, indicating induction of the adaptive arm of the immune system, which is responsible for long-term immunity. Based on this research, monoclonal antibodies programmed with improved effector function represent a potential new approach in the design of therapeutic antibodies for both the prevention and treatment of infectious diseases.

“By observing and learning from our body’s powerful natural defences, we have discovered how to maximise the capacity of antibodies through the amplification of key characteristics that may enable more effective treatments for viral diseases,” said Herbert “Skip” Virgin, study co-author and Executive VP, Research, and Chief Scientific Officer of Vir.

He said, “These data may have significant implications across a wide range of infectious diseases, and we look forward to exploring the vaccinal potential of the GAALIE-engineered antibodies we are advancing through clinical development – VIR-3434 for chronic hepatitis B and VIR-7832 for SARS-CoV-2.”

The preclinical study was conducted by Dr Ravetch and Stylianos Bournazos, of the Laboratory of Molecular Genetics and Immunology at The Rockefeller University, in collaboration with Dr Virgin and Davide Corti, Sr VP of antibody research at Vir’s subsidiary Humabs BioMed SA.

“This type of exceptional collaborative partnership between cutting-edge science and clinical application has the potential to significantly improve our ability to address infectious diseases,” stated Dr Virgin.

Vir is currently evaluating several monoclonal antibodies that have been Fc engineered to include the XX2 “vaccinal mutation” (or GAALIE variant) for which Vir has licensed exclusive rights for all infectious diseases.