Passive immunization of Ebola virus-infected cynomolgus monkeys with immunoglobulin from hyperimmune horses

Jahrling, Peter B.; Geisbert, Joan B.; Swearengen, James R.; Jaax, Gerald P.; Lewis, Thomas B.; Huggins, John W.; Schmidt, J; LeDuc, James W.; Peters, C. J.

doi:10.1007/978-3-7091-7482-1_12

Cited by 117 publications

(124 citation statements)

References 6 publications

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“…The EBOV used in this study was originally obtained from a fatally infected human from the former Zaire in 1995. 15 Inoculated animals were monitored twice each day for signs of illness. Scheduled necropsies were performed at 1 (n ϭ 3), 2 (n ϭ 3), 3 (n ϭ 4), 4 (n ϭ 4), 5 (n ϭ 4), and 6 (n ϭ 3) days postinfection.…”

Section: Animals and Inoculationsmentioning

confidence: 99%

“…Several nonhuman primate species have been used to model EBOV (Zaire) HF including African green monkeys (Chlorocebus aethiops, formerly Cercopithecus aethiops), 4,5,14 cynomolgus macaques (Macaca fascicularis), 5,7,[15][16][17] rhesus macaques (Macaca mulatta), 4 -7,18 -20 and hamadryad baboons (Papio hamadryas). [21][22][23][24][25][26] Similar pathological features of EBOV infection have been documented among these species; however, African green monkeys do not present with a macular cutaneous rash, which is a characteristic feature of disease in macaques and baboons.…”

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confidence: 99%

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Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

Geisbert

Hensley

Larsen

et al. 2003

The American Journal of Pathology

525

327

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Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined sequentially over a 6-day period to investigate the pathological events of EBOV infection that lead to death. Importantly, dendritic cells in lymphoid tissues were identified as early and sus-

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Section: Animals and Inoculationsmentioning

confidence: 99%

mentioning

confidence: 99%

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

Geisbert

Hensley

Larsen

et al. 2003

The American Journal of Pathology

525

327

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show abstract

“…Initial success was achieved by using similar IgG preparations in hamadryas baboons, in which the equine IgG was protective against lethal EBOV challenge (10-12). In contrast, cynomolgus macaques receiving the commercially available equine IgG product did not survive challenge with EBOV, although the onsets to clinical signs and viremia, and time to death, were delayed relative to controls (9,13). From these studies, it appeared that the antibody was able to control viremia while present, but when the antibody had been depleted, presumably by complexing with virus or immune clearance because of its heterologous nature, the disease progressed unabated.…”

mentioning

confidence: 95%

“…The lethality rate (12.5%) from this treatment was significantly lower than the overall case fatality rate for the outbreak (80%); however, interpreting the role of antibodies in the achieved protection is complicated because the patients received whole blood, not just antibodies, in addition to supportive care in a hospital setting. After the 1995 outbreak, the World Health Organization procured a commercially available equine IgG product produced from horses hypervaccinated with EBOV for potential use in humans (9). Initial success was achieved by using similar IgG preparations in hamadryas baboons, in which the equine IgG was protective against lethal EBOV challenge (10-12).…”

mentioning

confidence: 99%

Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease

Dye

Herbert²,

Kuehne³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

242

215

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Antibody therapies to prevent or limit filovirus infections have received modest interest in recent years, in part because of early negative experimental evidence. We have overcome the limitations of this approach, leveraging the use of antibody from nonhuman primates (NHPs) that survived challenge to filoviruses under controlled conditions. By using concentrated, polyclonal IgG antibody from these survivors, we treated filovirus-infected NHPs with multiple doses administered over the clinical phase of disease. In the first study, Marburg virus (MARV)-infected NHPs were treated 15 to 30 min postexposure with virus-specific IgG, with additional treatments on days 4 and 8 postexposure. The postexposure IgG treatment was completely protective, with no signs of disease or detectable viremia. MARV-specific IgM antibody responses were generated, and all macaques survived rechallenge with MARV, suggesting that they generated an immune response to virus replication. In the next set of studies, NHPs were infected with MARV or Ebola virus (EBOV), and treatments were delayed 48 h, with additional treatments on days 4 and 8 postexposure. The delayed treatments protected both MARV- and EBOV-challenged NHPs. In both studies, two of the three IgG-treated NHPs had no clinical signs of illness, with the third NHP developing mild and delayed signs of disease followed by full recovery. These studies clearly demonstrate that postexposure antibody treatments can protect NHPs and open avenues for filovirus therapies for human use using established Food and Drug Administration-approved polyclonal or monoclonal antibody technologies.

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“…Studies using monoclonal antibodies and immune serum in cell culture and in animals have also suggested that antibody can protect against ZEBOV [18,20,53,78,112,113]. Hyper-immune equine sera, however, was unable to protect cynomolgus macaques from ZEBOV, although under some circumstances, it did delay viremia and time to death [114]. Antibody-mediated enhancement of infection in cell culture has been reported for VSV expressing ZEBOV GP [115]; however, other laboratories have not observed this effect [116].…”

Section: Immunological Correlates and Mechanismsmentioning

confidence: 99%