==EBOLA ANTIBODIES== J Virol 2001 Mar;75(5):2324-30 Infectivity-enhancing antibodies to Ebola virus glycoprotein. Takada A, Watanabe S, Okazaki K, Kida H, Kawaoka Y. Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Ebola virus causes severe hemorrhagic fever in primates, resulting in mortality rates of up to 100%, yet there are no satisfactory biologic explanations for this extreme virulence. Here we show that antisera produced by DNA immunization with a plasmid encoding the surface glycoprotein (GP) of the Zaire strain of Ebola virus enhances the infectivity of vesicular stomatitis virus pseudotyped with the GP. Substantially weaker enhancement was observed with antiserum to the GP of the Reston strain, which is much less pathogenic in humans than the Ebola Zaire and Sudan viruses. The enhancing activity was abolished by heat but was increased in the presence of complement system inhibitors, suggesting that heat-labile factors other than the complement system are required for this effect. We also generated an anti-Zaire GP monoclonal antibody that enhanced viral infectivity and another that neutralized it, indicating the presence of distinct epitopes for these properties. Our findings suggest that antibody-dependent enhancement of infectivity may account for the extreme virulence of the virus. They also raise issues about the development of Ebola virus vaccines and the use of passive prophylaxis or therapy with Ebola virus GP antibodies. Cell Mol Life Sci 2001 Nov;58(12-13):1826-41 Ebola virus: the search for vaccines and treatments. Wilson JA, Bosio CM, Hart MK. Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA. Ebola viruses belong to the family Filoviridae, which are among the most virulent infectious agents known. These viruses cause acute, and frequently fatal, hemorrhagic fever in humans and nonhuman primates. Currently, no vaccines or treatments are available for human use. This review describes Ebola viruses, with a particular focus on the status of research efforts to develop vaccines and therapeutics and to identify the immune mechanisms of protection. Trans Am Clin Climatol Assoc 2001;112:79-84; discussion 86-8 The Gordon Wilson Lecture: viruses and human disease. Nabel GJ. Vaccine Research Center, National Institutes of Health, 40 Convent Drive, MSC-3005, Bethesda, MD 20892, USA. gnabel@mail.nih.gov In many ways, Ebola virus infection provides a model for understanding the toxicity of viruses and their causal role in human disease. The highly aggressive course of Ebola virus infection provides a model for understanding the molecular mechanisms of viral cytotoxicity. In addition, the use of animal models and definition of immune correlates, which lead to protection, may provide lessons that are applicable to other viral infections. Perhaps the greatest challenge facing biomedical science today is the containment of the human immunodeficiency virus, the causative agent of AIDS. In many ways the critical obstacles to the development of a vaccine for HIV are similar to those observed with Ebola virus infection. Because the reservoir of infection is not known and human-to-human spread has been documented, vaccines may provide the best opportunity to contain and limit the spread of infection worldwide. Similar to Ebola virus, there are few convincing examples of immune resistance of HIV infection. In addition, it has been difficult to identify broadly neutralizing antibodies that can prevent infection in vitro or in vivo. In defining immune correlates, relevant animal models, and mechanisms of cytotoxicity, it is hoped that similar efforts may lead to effective vaccines for other infectious diseases. In this way, Ebola virus infection provides a useful paradigm for understanding the genetic determinants of viral disease and in facilitating the development of treatments and prevention of viral infections. J Virol 2001 Mar;75(5):2324-30 Infectivity-enhancing antibodies to Ebola virus glycoprotein. Takada A, Watanabe S, Okazaki K, Kida H, Kawaoka Y. Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. Ebola virus causes severe hemorrhagic fever in primates, resulting in mortality rates of up to 100%, yet there are no satisfactory biologic explanations for this extreme virulence. Here we show that antisera produced by DNA immunization with a plasmid encoding the surface glycoprotein (GP) of the Zaire strain of Ebola virus enhances the infectivity of vesicular stomatitis virus pseudotyped with the GP. Substantially weaker enhancement was observed with antiserum to the GP of the Reston strain, which is much less pathogenic in humans than the Ebola Zaire and Sudan viruses. The enhancing activity was abolished by heat but was increased in the presence of complement system inhibitors, suggesting that heat-labile factors other than the complement system are required for this effect. We also generated an anti-Zaire GP monoclonal antibody that enhanced viral infectivity and another that neutralized it, indicating the presence of distinct epitopes for these properties. Our findings suggest that antibody-dependent enhancement of infectivity may account for the extreme virulence of the virus. They also raise issues about the development of Ebola virus vaccines and the use of passive prophylaxis or therapy with Ebola virus GP antibodies. J Virol 1999 Jul;73(7):6024-30 Ebola virus can be effectively neutralized by antibody produced in natural human infection. Maruyama T, Rodriguez LL, Jahrling PB, Sanchez A, Khan AS, Nichol ST, Peters CJ, Parren PW, Burton DR. Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA. The activity of antibodies against filoviruses is poorly understood but has important consequences for vaccine design and passive prophylaxis. To investigate this activity, a panel of recombinant human monoclonal antibodies to Ebola virus antigens was isolated from phage display libraries constructed from RNA from donors who recovered from infection in the 1995 Ebola virus outbreak in Kikwit, Democratic Republic of Congo. Antibodies reactive with nucleoprotein (NP), envelope glycoprotein (GP), and secreted envelope glycoprotein (sGP) were characterized by immunofluorescence and radioimmunoprecipitation assays. Four antibodies reacting strongly with sGP and weakly with GP and two antibodies reacting with NP were not neutralizing. An antibody specific for GP neutralized Ebola virus to 50% at 0.4 microgram/ml as the recombinant Fab fragment and to 50% at 0.3 microgram/ml (90% at 2.6 microgram/ml) as the corresponding whole immunoglobulin G1 molecule. The studies indicate that neutralizing antibodies are produced in infection by Ebola virus although probably at a relatively low frequency. The neutralizing antibody may be useful in vaccine design and as a prophylactic agent against Ebola virus infection. Vestn Ross Akad Med Nauk 1998;(4):24-9 [Developing methods of specific heterologic immunoglobulins preparation for urgent prevention of Ebola fever and study of their properties] [Article in Russian] Cherpunov AA, Kudoiarova-Zubavichene NM, Dedkova LM, Sergeev NN, Netesov SV. Methods for preventing and treating Ebola virus hemorrhagic fever are not still available despite the fact that this virus have been studied for 20 years. Methods of immunization of the animals (sheep, goats) non-susceptible to Ebola virus with live virus preparations were developed to obtain the hyperimmune anti-Ebola virus sera required to have highly immune antivirus gamma-globulins. These methods made it possible to obtain the immune sera having high virus-neutralizing antibodies. Caprine immunoglobulins were obtained from sera by fractionation of immune sera by Kohn's method. The neutralization indices of the immunoglobulins obtained were at least Ig. When administered in the first hours of infection, the protective effect of these preparations was shown on guinea pigs infected with LD50 of the strain pathogenic to the animals. Preclinical trials of these immunoglobulins on laboratory animals and clinical trials on volunteers were performed. The preparation was used as a preventive agent when accidents took place at the laboratory working with Ebola virus. The similar preparation from equine sera having high neutralizing and protective properties was elaborated at the Virological Center, Microbiological Institute, Russian Ministry of Defense. Its prophylactic efficiency was also shown in infected gamadrias.