Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

Golden, Joseph W.; Hammerbeck, Christopher; Mucker, Eric M.; Brocato, Rebecca L.

doi:10.1155/2015/793257

Cited by 51 publications

(59 citation statements)

References 279 publications

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“…Protective efficacy of DNA vaccine-produced anti-glycoprotein neutralizing antibody. Human disease caused by South American arenaviruses can be recapitulated in guinea pig and nonhuman primate animal models (50,51). We used outbred strain Hartley guinea pigs to determine if DNA vaccine-produced neutralizing antibodies could protect a heterogeneous population against lethal viral disease caused by JUNV strain Romero.…”

Section: Discussionmentioning

confidence: 99%

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

Golden

Maes

Kwilas

et al. 2016

J Virol

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Several members of the Arenaviridae can cause acute febrile diseases in humans, often resulting in lethality. The use of convalescent-phase human plasma is an effective treatment in humans infected with arenaviruses, particularly species found in South America. Despite this, little work has focused on developing potent and defined immunotherapeutics against arenaviruses. In the present study, we produced arenavirus neutralizing antibodies by DNA vaccination of rabbits with plasmids encoding the full-length glycoprotein precursors of Junín virus (JUNV), Machupo virus (MACV), and Guanarito virus (GTOV). Geometric mean neutralizing antibody titers, as measured by the 50% plaque reduction neutralization test (PRNT 50 ), exceeded 5,000 against homologous viruses. Antisera against each targeted virus exhibited limited cross-species binding and, to a lesser extent, cross-neutralization. Anti-JUNV glycoprotein rabbit antiserum protected Hartley guinea pigs from lethal intraperitoneal infection with JUNV strain Romero when the antiserum was administered 2 days after challenge and provided some protection (ϳ30%) when administered 4 days after challenge. Treatment starting on day 6 did not protect animals. We further formulated an IgG antibody cocktail by combining anti-JUNV, -MACV, and -GTOV antibodies produced in DNA-vaccinated rabbits. This cocktail protected 100% of guinea pigs against JUNV and GTOV lethal disease. We then expanded on this cocktail approach by simultaneously vaccinating rabbits with a combination of plasmids encoding glycoproteins from JUNV, MACV, GTOV, and Sabia virus (SABV). Sera collected from rabbits vaccinated with the combination vaccine neutralized all four targets. These findings support the concept of using a DNA vaccine approach to generate a potent pan-arenavirus immunotherapeutic. IMPORTANCEArenaviruses are an important family of emerging viruses. In infected humans, convalescent-phase plasma containing neutralizing antibodies can mitigate the severity of disease caused by arenaviruses, particularly species found in South America. Because of variations in potency of the human-derived product, limited availability, and safety concerns, this treatment option has essentially been abandoned. Accordingly, despite this approach being an effective postinfection treatment option, research on novel approaches to produce potent polyclonal antibody-based therapies have been deficient. Here we show that DNA-based vaccine technology can be used to make potently neutralizing antibodies in rabbits that exclusively target the glycoproteins of several human-pathogenic arenaviruses found in South America, including JUNV, MACV, GTOV, and SABV. These antibodies protected guinea pigs from lethal disease when given post-virus challenge. We also generated a purified antibody cocktail with antibodies targeting three arenaviruses and demonstrated protective efficacy against all three targets. Our findings demonstrate that use of the DNA vaccine technology could be used to produce candidate antiarenavirus ne...

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Section: Discussionmentioning

confidence: 99%

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

Golden

Maes

Kwilas

et al. 2016

J Virol

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“…It is used as a model in multiple infectious diseases studies including Nipah virus (Wong et al, 2003), Hanta virus (Hammerbeck and Hooper, 2011), Clostridium difficile (Goulding et al, 2009) and safety testing of leptospirosis vaccines (Haake, 2006) and reviewed in Golden et al, 2015a, Golden et al, 2015b. Of particular interest to us is its usefulness as a small animal model for research into malignant catarrhal fever in ruminants (Buxton et al, 1988, Jacoby et al, 1988, Russell et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Characterisation of monoclonal antibodies specific for hamster leukocyte differentiation molecules

Rees

Haig

Mack

et al. 2017

Veterinary Immunology and Immunopathology

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Flow cytometry was used to identify mAbs that recognize conserved epitopes on hamster leukocyte differentiation molecules (hLDM) and also to characterize mAbs developed against hLDM. Initial screening of mAbs developed against LDMs in other species yielded mAbs specific for the major histocompatibility (MHC) II molecule, CD4 and CD18. Screening of sets of mAbs developed against hLDM yielded 22 new mAbs, including additional mAbs to MHC II molecules and mAbs that recognize LDMs expressed on all leukocytes, granulocytes, all lymphocytes, all T cells, a subset of T cells, or on all B cells. Based on comparison of the pattern of expression of LDMs expressed on all hamster leukocytes with the patterns of expression of known LDMs in other species, as detected by flow cytometry (FC), four mAbs are predicted to recognize CD11a, CD44, and CD45. Cross comparison of mAbs specific for a subset of hamster T cells with a cross reactive mAb known to recognize CD4 in mice and one recognising CD8 revealed they recognize CD4. The characterization of these mAbs expands opportunities to use hamsters as an additional model species to investigate the mechanisms of immunopathogenesis of infectious diseases.

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“…MPRLV, which does not cause disease in humans, causes partial lethality and HPS‐like disease in these hamsters . This makes the Syrian hamster model currently the best Hantavirus infection and HPS‐disease model, making it well suited to study the antiviral efficacy of small molecule inhibitors …”

Section: Replication Cyclementioning

confidence: 99%

Structural and functional similarities in bunyaviruses: Perspectives for pan‐bunya antivirals

Horst

Conceição-Neto

Neyts

et al. 2019

Reviews in Medical Virology

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The order of Bunyavirales includes numerous (re)emerging viruses that collectively have a major impact on human and animal health worldwide. There are no vaccines for human use or antiviral drugs available to prevent or treat infections with any of these viruses. The development of efficacious and safe drugs and vaccines is a pressing matter. Ideally, such antivirals possess pan-bunyavirus antiviral activity, allowing the containment of every bunya-related threat. The fact that many bunyaviruses need to be handled in laboratories with biosafety level 3 or 4, the great variety of species and the frequent emergence of novel species complicate such efforts. We here examined the potential druggable targets of bunyaviruses, together with the level of conservation of their biological functions, structure, and genetic similarity by means of heatmap analysis. In the light of this, we revised the available models and tools currently available, pointing out directions for antiviral drug discovery.

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Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

Cited by 51 publications

References 279 publications

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever

Characterisation of monoclonal antibodies specific for hamster leukocyte differentiation molecules

Structural and functional similarities in bunyaviruses: Perspectives for pan‐bunya antivirals

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