Respiratory infections such as coronaviruses, influenza and respiratory syncytial viruses enter the body via mucosal surfaces in the nose, eyes and mouth. We’re developing a novel class of antibody and delivery technologies to provide enhanced protection and improved therapeutic performance for coronaviruses and other respiratory infections. We aim to develop the world’s first mucosally therapeutic for treatment of respiratory infection and pre-exposure prophylactic antibodies for the prevention infections.
2022–ongoing.
Dimeric IgA (dIgA) is a direct precursor of secretory IgA (SIgA) and exerts multiple functions to protect against pathogens or toxins at mucosal surfaces. These include direct neutralisation that blocks pathogen entry activity or binding to effector cells to activate cellular processes to enhance pathogen clearance.
Secretory IgA is highly abundant in saliva, tears and mucosal secretions from the nose and provides an essential barrier against infections. Dimeric IgA is actively transported across mucosal surfaces and converted to SIgA, which is 3-10-fold more abundant than IgG in tears and saliva.
Current therapeutic and prophylactic antibodies have not harnessed the naturally protective properties of IgA. Instead, they rely on IgG which is only passively transported across mucosal surfaces. We’re examining whether dIgA and SIgA antibodies have enhanced ability to protect and treat respiratory infections.
Dimeric IgA is actively transported across mucosal surfaces. Compared to IgG antibodies, it should provide enhanced protection against SARS-CoV-2 and improved therapeutic performance in COVID-19 treatment. Formulation as a nasal spray containing secretory IgA may provide barrier protection against SARS-CoV-2 at the mucosa.
Use of dIgA or SIgA isotypes may lower dosing requirements compared with IgG formulations. This will provide a cost benefit to manufacturers and consumers and provide improved performance compared to IgG based therapeutics.
Our antibody system is a platform technology. It could be adapted for other pathogens for which no vaccines or treatments are currently available. These include norovirus and other enteric and mucosal pathogens.
Immunocompromised people who do not generate protective immunity through vaccination may also benefit from IgA based prophylactics and treatments, protecting against the severe consequences of infection.
Immunoglobulin A (IgA) has been under-utilized for therapeutics. In the sera IgA presents as a monomer while dimeric IgA (dIgA) predominates at mucosal surfaces. Here it interacts with the polymeric Immunoglobulin receptor generating secretory IgA (SIgA); an important defense at mucosal surfaces implicated in transmission prevention of mucosal pathogens, including respiratory pathogens. We are developing a dIgA prophylactics and therapeutics platform (DPAT) pipleline for the re-engineering of potent IgG sequences to the different IgA formats (monomeric, dimeric and secretory).
Student opportunities are available for different aspects of the IgA therapeutics platform including:
The outcome of these projects will be incorporation into our DPAT platform pipeline.
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Immunology and Cell Biology
Zihui Wei, Fiona Angrisano, Huy Trần Văn, Shuning Zheng, Rob J. Center, Irene Boo, Shazia Ruybal‐Pesántez, Leanne J. Robinson, David A. Anderson, Heidi E. Drummer
medRxiv (Cold Spring Harbor Laboratory)
Zihui Wei, Heidi E. Drummer, Huy Trần Văn, Shuning Zheng, Irene Boo, Rob J. Center, Li Fan, Rosemary Ffrench, David A. Anderson, Heidi E. Drummer
Microbiology Spectrum
Khayriyyah Mohd Hanafiah, David A. Anderson, Heidi E. Drummer