Leading Article

Clinical Immunotherapeutics

, Volume 1, Issue 4, pp 245-249

First online:

Monoclonal Antibodies in Rabies Therapy

  • Bernhard DietzscholdAffiliated withDepartment of Microbiology and Immunology, Center for Neurovirology, Jefferson Alumni Hall #459, Thomas Jefferson University

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Virus-neutralising antibodies play a major role in immunological protection against rabies. A combination of anti-rabies immunoglobulin and vaccine has become the standard World Health Organization treatment for humans with severe exposure to rabies virus. Equine anti-rabies serum (ERIG) and human rabies immunoglobulin (HRIG) are currently used for rabies post-exposure serotherapy. These products are either extremely expensive or their use is associated with adverse effects, as in the case of ERIG. Therefore, it is desirable to replace ERIG and HRIG by more cost effective and safer products.

Recent studies have shown that passive immunisation of rodents with murine or human monoclonal antibodies (mAbs) specific for the G protein of rabies virus protects from the disease in a post-exposure situation. Such treatment can also abrogate a lethal rabies virus infection after the virus has entered the central nervous system. These findings indicate the great potential of antiviral mAbs as effective therapeutics against rabies. Because of their highly specific protective activity and the lack of major risks and adverse effects, these mAbs have a major advantage over hyperimmune globulins.

However, there still exist inherent problems in the clinical application of mAbs. The high immunogenicity of murine mAbs in humans and the risk of virus contamination of human mAb preparations represent major obstacles for the use of mAbs. Recombinant DNA technology can be used to humanise murine mAbs. This increases the biological half-life and minimises the possibility of adverse effects. The problem of possible virus contamination of mAb preparations can be overcome by the expression of the mAb in a heterologous system.