Discovery of human monoclonal antibodies against different viruses

The antibody discovery platform established by Dr. Craig Fenwick and Professor Giuseppe Pantaleo in the Division of Immunology and Allergy at the CHUV has a research focus to discover novel fully human antibodies to target established and emerging infectious diseases. Through the isolation of virus specific B cells in post-infected or vaccinated donors, the platform is able to screen through thousands of B cell clones to discover the rare antibodies that have the best neutralizing potency and bind regions of the viral protein that are highly conserved and less likely to mutate.

The platform combines an in depth experience in cellular immunology, primary cell cultures, development of sensitive high throughput biochemical assays, neutralization assays, molecular biology and virology expertise to discover antibodies with best-in-class properties. Our recently discovered anti-COVID antibodies, P5C3 and P2G3, target two distinct sites on the viral Spike protein and are each the most potent and broad neutralizing antibodies binding their respective sites as compared to marketed and clinically advanced anti-SARS-COV-2 antibodies. In binding two separate and highly conserved sites on Spike, this combined therapy is highly potent against all current variants and binding in regions that will be difficult to mutate simultaneously in future SARS-COV-2 variants of concern.

Apart from identifying antibodies with potent cell culture based neutralization activity, the antibody discovery platform has strong collaborations with different groups throughout Europe for testing anti-viral efficacy in animal models. In studies performed with Professor Roger LeGrand at the CEA in France, we demonstrated that P2G3 alone confers complete prophylactic protection when administered to monkeys prior to infection with SARS-CoV-2 Omicron virus. P2G3 used in combination with P5C3 also confers excellent therapeutic efficacy in clearing virus and inhibiting active viral replication of the Omicron variant with administration of the antibody cocktail after infection of the monkeys.

Procedure for the isolation of COVID-19 specific B cells and the identification of potent neutralizing antibodies.

1. Continued evaluation of potent neutralizing antibodies against the SARS-COV-2 variants of concern binding distinct highly conserved epitopes on the viral Spike protein
2. Optimization of HIV interface neutralizing antibodies