Summary
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.
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References
Steele HH. Rabies in the Americas and remarks on global aspects. Rev Infect Dis 1988; 10 (Suppl. 4): 585–97
Baer GM. Research towards rabies prevention: overview. Rev Infect Dis 1988; 10 (Suppl. 4): 576–8
Dietzschold B, Tollis M, Lafon M, et al. Mechanisms of rabies virus neutralization by glycoprotein-specific monoclonal antibodies. Virology 1987; 161: 29–36
Davis DR, Metzger H. Structural basis of antibody function. Annu Rev Immunol 1983; 1: 87–117
Dietzschold B, Ertl HCJ. New developments in the pre- and post-exposure treatment of rabies. Crit Rev Immunol 1991; 10: 427–39
Dietzschold B, Kao M, Zheng YM, et al. Delineation of putative mechanisms involved in antibody-mediated clearance of rabies virus from the central nervous system. Proc Natl Acad Sci USA 1992; 89: 7252–6
Dietzschold B. Antibody-mediated clearance of viruses from the mammalian central nervous system. Trends Microbiol 1993; 1: 63–5
Wiktor TJ, Koprowski H. Monoclonal antibodies against rabies virus produced by somatic cell hybridization: detection of antigenic variants. Proc Natl Acad Sci USA 1978; 75: 3938–40
Ueki Y, Goldfarb IS, Harindranath N, et al. Clonal analysis of a human antibody response: quantitation of precursors and antibody-producing cells and characterization of monoclonal IgM, IgG, and IgA to rabies virus. J Exp Med 1990; 171: 19–34
Dietzschold B, Gore M, Casale P, et al. Biological characterization of human monoclonal antibodies to rabies virus. J Virol 1990; 64: 3087–90
Turner GS. Immunoglobulin (IgG and IgM) antibody responses to rabies vaccine. J Gen Virol 1978; 40: 595–604
Schumacher CL, Dietzschold B, Ertl HCJ, et al. Use of mouse anti-rabies monoclonal antibodies in post-exposure treatment of rabies. J Clin Invest 1989; 84: 971–5
Sears H, Herlyn D, Steplewski Z, et al. Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma. J Biol Resp Mod 1984; 3: 138–50
Massuci G, Ragnhammer P, Frödin JE, et al. Chemotherapy and immunotherapy of colorectal cancer. Med Oncol Tumor Pharmacother 1991; 8: 207–20
Reichman L, Clark M, Waldman H, et al. Reshaping human antibodies for therapy. Nature 1988; 332: 323–7
Co MS, Deschamps M, Whitley RJ, et al. Humanized antibodies for antiviral therapy. Proc Natl Acad Sci USA 1991; 88: 2869–73
Hasemann CA, Capra JD. High-level production of a functional immunoglobulin heterodimer in a baculovirus expression system. Proc Natl Acad Sci USA 1990; 87: 3942–6
Cheung SC, Dietzschold B, Koprowski H, et al. A recombinant human Fab expressed in Escherichia coli neutralizes rabies virus. J Virol 1992; 66: 6714–20
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Dietzschold, B. Monoclonal Antibodies in Rabies Therapy. Clin. Immunother. 1, 245–249 (1994). https://doi.org/10.1007/BF03259250
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DOI: https://doi.org/10.1007/BF03259250