Antibodies
Antibodies are proteins made naturally by cells of the body’s immune system. They function as one of the body’s principal defense mechanisms against pathogens, which are disease causing agents such as parasites, viruses or bacteria. Antibodies recognize and bind to invading pathogens, ultimately eliminating them, thus playing a crucial role in protecting humans against disease.
Influenza antibodies H1N1 and H5N1
There is a growing fear within the medical community concerning the potential reoccurrence of a pandemic influenza outbreak, similar to the 1918 ‘Spanish flu’ pandemic. A pandemic can start when a new influenza virus subtype emerges that meets three conditions: it infects humans causing serious illness; it spreads easily; and there is sustained human-to-human transmission of the virus.
Crucell has discovered the first human monoclonal antibodies for the prevention and treatment of the ‘bird flu’ strain H5N1, as well as H1N1, which is similar to the strain responsible for the devastating pandemic in 1918. The antibodies provide immediate protection and neutralize a broad range of H5N1 and H1N1 strains in pre-clinical models. In December 2008, Crucell presented data showing that the mAb CR6261 was 100% successful in preventing infection with H5N1. When given after H5N1 infection, Crucell’s mAb demonstrated the ability to prevent death and cure disease in all cases. The mAb also performed significantly better than the anti-influenza drug oseltamivir for the prevention and treatment of H1N1 infection, illustrating the potential use for seasonal applications as well. This is especially important as the resistance of influenza strains for oseltamivir is rapidly increasing.
Rabies Antibody Combination
Globally, around 10 million people a year are treated after exposure to rabies virus. Nevertheless, between 40,000 and 70,000 people die of rabies each year, mainly in Africa, China and India. This highlights the significant unmet medical need for a safe, effective and affordable rabies treatment. The approach currently used to prevent symptomatic disease and death in people exposed to rabies virus combines immunoglobulins (antibodies prepared from human or equine blood) with the vaccine. Concerns about the safety and availability of blood-derived rabies antibodies have prompted the search for alternatives.
Using MAbstract® and PER.C6® technology, Crucell scientists in collaboration with the Thomas Jefferson University in Philadelphia and the US Centers for Disease Control and Prevention in Atlanta have discovered a combination of human monoclonal antibodies (mAbs) for the post-exposure treatment of rabies. Clinical testing of this mAb combination made good progress during 2008, leading to the presentation in October of very promising efficacy and safety data from a Phase II trial in the USA. In order to test the mAb combination in different populations and settings, additional Phase II trials were started in May 2008 (among children in the Philippines) and February 2009 (among adults in India).
Since January 2008, the route towards global availability of this next-generation, life-saving rabies biological is being facilitated by Crucell’s strategic partnership with sanofi pasteur, a world leader in rabies immunization. The US Food and Drug Administration (FDA) has granted Crucell’s mAb combination Fast Track status, which paves the way for priority handling of the regulatory dossier.