Development of broad-spectrum human antibodies for rabies post-exposure prophylaxis
Antibodies broadly neutralize a large panel of rabies and rabies-related viruses, and are up to 1,000 times more effective than existing treatments
Humabs BioMed SA, a Swiss antibody therapeutics company, today announced the identification, isolation and characterization of two monoclonal antibodies with broad-spectrum, high potency activity against rabies viruses. As published in this week’s EMBO Molecular Medicine, the combined antibodies showed higher potency and a broader activity compared to commercially available human rabies immunoglobulins (RIGs) and to other monoclonal antibodies under clinical development. RVC20 and RVC58 may provide a very effective and affordable alternative to existing post-exposure prophylaxis of rabies infection. The results were achieved in an international collaboration with leading research institutes from Switzerland, Italy, France and the UK.
Rabies is found worldwide in different animal reservoirs and is known to be a deadly viral infection with almost 100% fatality following the onset of symptoms. There is no treatment available. However, if exposed, there is a short window before the onset of symptoms for infected humans to be treated by vaccination and co-administration of rabies immunoglobulins that are prepared from human or equine blood. This so-called post-exposure prophylaxis (PEP) must be administered as early as possible and is ineffective after the onset of symptoms. The high cost and limited availability of PEP is a huge problem in many remote areas in the poor parts of the world. Only about 1 million doses of rabies immunoglobulins are produced every year and sadly 60% of the people at high risk of developing rabies do not have access to them. Some 59,000 people are estimated to die each year, mainly in India, China and Africa, and 50% of rabies cases worldwide affect children. However, the true burden of rabies in developing countries is unknown and largely un-diagnosed. The transition from RIG to monoclonal antibody-based PEP is strongly recommended by the WHO with the aim to achieve adequate supply at affordable costs.
“Our development is in line with recommendations by the WHO to develop new, monoclonal antibody-based treatments for rabies post-exposure prophylaxis,” said Davide Corti, co-author of the paper and CSO of Humabs BioMed. “The antibody cocktail we identified and tested has high potency, targets distinct, non-overlapping antigens and broadly covers all known viruses. Moreover, the high potency of these antibodies demonstrated that only a very limited amount, as low as 3 milligrams per dose, is needed to protect humans from lethal infection.”
“The antibody cocktail has great potential,” said Paola De Benedictis, lead author of the paper and a virologist and veterinarian at the Istituto Zooprofilattico Sperimentale delle Venezie (Padua, Italy). “It may not only replace immunoglobins but it can also pave the way to a paradigm shift in rabies treatment. We noticed that in vivo even 40 days after administration of the antibodies, there was still a high neutralizing and potentially protective titer of the antibodies in the blood, so it may be possible that the prophylaxis window is widened considerably with RVC20 and RVC58.”
“Current post-exposure prophylaxis is very costly and supply is dwindling because of lack of human donors. Alternatives under development so far protect only against a limited spectrum of viruses, posing serious concerns for prophylaxis without virus characterization,” said Hervé Bourhy, co-author of the paper and Head of the WHO Collaborating Centre for Reference and Research on Rabies at Institut Pasteur (Paris, France). “The antibodies we characterized in vitro protect against a very broad spectrum of rabies viruses. Moreover, these antibodies could be formulated in ways not to require cooling, another important advantage in remote areas.”
“The isolation of these two antibodies is another validation of our approach that can lead to very potent antibodies against deadly infectious diseases,” added Filippo Riva, CEO of Humabs BioMed. “Within the past six months, we have demonstrated this in MERS, Ebola and now in Rabies. We are now seeking licensing opportunities on a worldwide basis and we are optimistic to start the development of these antibodies as soon as possible.”
Two of Humabs’ human-derived antibodies are in clinical development with the company’s partners MedImmune and Novartis.
