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David W. Hawman
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT 59840, USA

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Journal article
Published: 12 May 2021 in Microorganisms
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The 2019 novel coronavirus, SARS-CoV-2, first reported in December 2019, has infected over 102 million people around the world as of February 2021 and thus calls for rapid development of safe and effective interventions, namely vaccines. In our study, we evaluated a DNA vaccine against SARS-CoV-2 in the Syrian hamster model. Hamsters were vaccinated with a DNA-plasmid encoding the SARS-CoV-2 full length spike open reading frame (ORF) to induce host cells to produce spike protein and protective immune responses before exposure to infectious virus. We tested this vaccine candidate by both intranasal (IN) and intramuscular (IM) routes of administration and complexing with and without an in vivo delivery reagent. Hamsters receiving prime-boost-boost IM-only vaccinations recovered body weight quicker, had decreased lung viral loads, and increased SARS-CoV-2-specific antibody titers compared to control vaccinated animals but, surprisingly, lung pathology was as severe as sham vaccinated controls. The IM/IN combination group showed no efficacy in reducing lung virus titers or pathology. With increasing public health need for rapid and effective interventions, our data demonstrate that in some vaccine contexts, significant antibody responses and decreased viral loads may not be sufficient to prevent lung pathology.

ACS Style

Shanna Leventhal; Chad Clancy; Jesse Erasmus; Heinz Feldmann; David Hawman. An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters. Microorganisms 2021, 9, 1040 .

AMA Style

Shanna Leventhal, Chad Clancy, Jesse Erasmus, Heinz Feldmann, David Hawman. An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters. Microorganisms. 2021; 9 (5):1040.

Chicago/Turabian Style

Shanna Leventhal; Chad Clancy; Jesse Erasmus; Heinz Feldmann; David Hawman. 2021. "An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters." Microorganisms 9, no. 5: 1040.

Preprint content
Published: 04 April 2021
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Severe COVID-19 has been associated with T cell lymphopenia 1,2, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from SARS-CoV-2 infections we studied rhesus macaques that were depleted of either CD4+, CD8+ or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to controls. The T cell-depleted groups developed virus-neutralizing antibody responses and also class-switched to IgG. When re-infected six weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+ or CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory or protection from a second infection.

ACS Style

Kim J. Hasenkrug; Friederike Feldmann; Lara Myers; Mario L. Santiago; Kejun Guo; Bradley S. Barrett; Kaylee L. Mickens; Aaron Carmody; Atsushi Okumura; Deepashri Rao; Madison M. Collins; Ronald J. Messer; Jamie Lovaglio; Carl Shaia; Rebecca Rosenke; Neeltje van Doremalen; Chad Clancy; Greg Saturday; Patrick Hanley; Brian Smith; Kimberly Meade-White; W. Lesley Shupert; David W. Hawman; Heinz Feldmann. Recovery from acute SARS-CoV-2 infection and development of anamnestic immune responses in T cell-depleted rhesus macaques. 2021, 1 .

AMA Style

Kim J. Hasenkrug, Friederike Feldmann, Lara Myers, Mario L. Santiago, Kejun Guo, Bradley S. Barrett, Kaylee L. Mickens, Aaron Carmody, Atsushi Okumura, Deepashri Rao, Madison M. Collins, Ronald J. Messer, Jamie Lovaglio, Carl Shaia, Rebecca Rosenke, Neeltje van Doremalen, Chad Clancy, Greg Saturday, Patrick Hanley, Brian Smith, Kimberly Meade-White, W. Lesley Shupert, David W. Hawman, Heinz Feldmann. Recovery from acute SARS-CoV-2 infection and development of anamnestic immune responses in T cell-depleted rhesus macaques. . 2021; ():1.

Chicago/Turabian Style

Kim J. Hasenkrug; Friederike Feldmann; Lara Myers; Mario L. Santiago; Kejun Guo; Bradley S. Barrett; Kaylee L. Mickens; Aaron Carmody; Atsushi Okumura; Deepashri Rao; Madison M. Collins; Ronald J. Messer; Jamie Lovaglio; Carl Shaia; Rebecca Rosenke; Neeltje van Doremalen; Chad Clancy; Greg Saturday; Patrick Hanley; Brian Smith; Kimberly Meade-White; W. Lesley Shupert; David W. Hawman; Heinz Feldmann. 2021. "Recovery from acute SARS-CoV-2 infection and development of anamnestic immune responses in T cell-depleted rhesus macaques." , no. : 1.

Review
Published: 18 February 2021 in Viruses
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In 2016, the Bunyavirales order was established by the International Committee on Taxonomy of Viruses (ICTV) to incorporate the increasing number of related viruses across 13 viral families. While diverse, four of the families (Peribunyaviridae, Nairoviridae, Hantaviridae, and Phenuiviridae) contain known human pathogens and share a similar tri-segmented, negative-sense RNA genomic organization. In addition to the nucleoprotein and envelope glycoproteins encoded by the small and medium segments, respectively, many of the viruses in these families also encode for non-structural (NS) NSs and NSm proteins. The NSs of Phenuiviridae is the most extensively studied as a host interferon antagonist, functioning through a variety of mechanisms seen throughout the other three families. In addition, functions impacting cellular apoptosis, chromatin organization, and transcriptional activities, to name a few, are possessed by NSs across the families. Peribunyaviridae, Nairoviridae, and Phenuiviridae also encode an NSm, although less extensively studied than NSs, that has roles in antagonizing immune responses, promoting viral assembly and infectivity, and even maintenance of infection in host mosquito vectors. Overall, the similar and divergent roles of NS proteins of these human pathogenic Bunyavirales are of particular interest in understanding disease progression, viral pathogenesis, and developing strategies for interventions and treatments.

ACS Style

Shanna Leventhal; Drew Wilson; Heinz Feldmann; David Hawman. A Look into Bunyavirales Genomes: Functions of Non-Structural (NS) Proteins. Viruses 2021, 13, 314 .

AMA Style

Shanna Leventhal, Drew Wilson, Heinz Feldmann, David Hawman. A Look into Bunyavirales Genomes: Functions of Non-Structural (NS) Proteins. Viruses. 2021; 13 (2):314.

Chicago/Turabian Style

Shanna Leventhal; Drew Wilson; Heinz Feldmann; David Hawman. 2021. "A Look into Bunyavirales Genomes: Functions of Non-Structural (NS) Proteins." Viruses 13, no. 2: 314.

Journal article
Published: 29 January 2021 in Microorganisms
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Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. In humans, the disease follows infection by the Crimean-Congo hemorrhagic fever virus (CCHFV) and begins as flu-like symptoms that can rapidly progress to hemorrhaging and death. Case fatality rates can be as high as 30%. An important gap in our understanding of CCHF are the host immune responses necessary to control the infection. A better understanding of these responses is needed to direct therapeutic strategies to limit the often-severe morbidity and mortality seen in humans. In this report, we have utilized a mouse model in which mice develop severe disease but ultimately recover. T-cells were robustly activated, differentiated to produce antiviral cytokines, and were critical for survival following CCHFV infection. We further identified a key role for interferon gamma (IFNγ) in survival following CCHFV infection. These results significantly improve our understanding of the host adaptive immune response to severe CCHFV infection.

ACS Style

David Hawman; Kimberly Meade-White; Shanna Leventhal; Aaron Carmody; Elaine Haddock; Kim Hasenkrug; Heinz Feldmann. T-Cells and Interferon Gamma Are Necessary for Survival Following Crimean-Congo Hemorrhagic Fever Virus Infection in Mice. Microorganisms 2021, 9, 279 .

AMA Style

David Hawman, Kimberly Meade-White, Shanna Leventhal, Aaron Carmody, Elaine Haddock, Kim Hasenkrug, Heinz Feldmann. T-Cells and Interferon Gamma Are Necessary for Survival Following Crimean-Congo Hemorrhagic Fever Virus Infection in Mice. Microorganisms. 2021; 9 (2):279.

Chicago/Turabian Style

David Hawman; Kimberly Meade-White; Shanna Leventhal; Aaron Carmody; Elaine Haddock; Kim Hasenkrug; Heinz Feldmann. 2021. "T-Cells and Interferon Gamma Are Necessary for Survival Following Crimean-Congo Hemorrhagic Fever Virus Infection in Mice." Microorganisms 9, no. 2: 279.

Journal article
Published: 08 January 2021 in eLife
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Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

ACS Style

David W Hawman; Kimberly Meade-White; Shanna Leventhal; Friederike Feldmann; Atsushi Okumura; Brian Smith; Dana Scott; Heinz Feldmann. Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus. eLife 2021, 10, 1 .

AMA Style

David W Hawman, Kimberly Meade-White, Shanna Leventhal, Friederike Feldmann, Atsushi Okumura, Brian Smith, Dana Scott, Heinz Feldmann. Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus. eLife. 2021; 10 ():1.

Chicago/Turabian Style

David W Hawman; Kimberly Meade-White; Shanna Leventhal; Friederike Feldmann; Atsushi Okumura; Brian Smith; Dana Scott; Heinz Feldmann. 2021. "Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus." eLife 10, no. : 1.

Preprint content
Published: 05 November 2020
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Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

ACS Style

David W. Hawman; Kimberly Meade-White; Shanna Leventhal; Friederike Feldmann; Atsushi Okumura; Brian Smith; Dana Scott; Heinz Feldmann. Immunocompetent Mouse Model for Crimean-Congo Hemorrhagic Fever Virus. 2020, 1 .

AMA Style

David W. Hawman, Kimberly Meade-White, Shanna Leventhal, Friederike Feldmann, Atsushi Okumura, Brian Smith, Dana Scott, Heinz Feldmann. Immunocompetent Mouse Model for Crimean-Congo Hemorrhagic Fever Virus. . 2020; ():1.

Chicago/Turabian Style

David W. Hawman; Kimberly Meade-White; Shanna Leventhal; Friederike Feldmann; Atsushi Okumura; Brian Smith; Dana Scott; Heinz Feldmann. 2020. "Immunocompetent Mouse Model for Crimean-Congo Hemorrhagic Fever Virus." , no. : 1.

Research article
Published: 20 July 2020 in Science Translational Medicine
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The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale up. Here, we developed an Alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with lipid inorganic nanoparticles (LIONs) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti–SARS-CoV-2 S protein IgG antibody isotypes indicative of a type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in the lung and spleen. Prime-only immunization of aged (17 months old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. In nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in five intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.

ACS Style

Jesse H. Erasmus; Amit P. Khandhar; Megan A. O’Connor; Alexandra C. Walls; Emily A. Hemann; Patience Murapa; Jacob Archer; Shanna Leventhal; James T. Fuller; Thomas B. Lewis; Kevin E. Draves; Samantha Randall; Kathryn A. Guerriero; Malcolm S. Duthie; Darrick Carter; Steven G. Reed; David W. Hawman; Heinz Feldmann; Michael Gale; David Veesler; Peter Berglund; Deborah Heydenburg Fuller. An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates. Science Translational Medicine 2020, 12, eabc9396 .

AMA Style

Jesse H. Erasmus, Amit P. Khandhar, Megan A. O’Connor, Alexandra C. Walls, Emily A. Hemann, Patience Murapa, Jacob Archer, Shanna Leventhal, James T. Fuller, Thomas B. Lewis, Kevin E. Draves, Samantha Randall, Kathryn A. Guerriero, Malcolm S. Duthie, Darrick Carter, Steven G. Reed, David W. Hawman, Heinz Feldmann, Michael Gale, David Veesler, Peter Berglund, Deborah Heydenburg Fuller. An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates. Science Translational Medicine. 2020; 12 (555):eabc9396.

Chicago/Turabian Style

Jesse H. Erasmus; Amit P. Khandhar; Megan A. O’Connor; Alexandra C. Walls; Emily A. Hemann; Patience Murapa; Jacob Archer; Shanna Leventhal; James T. Fuller; Thomas B. Lewis; Kevin E. Draves; Samantha Randall; Kathryn A. Guerriero; Malcolm S. Duthie; Darrick Carter; Steven G. Reed; David W. Hawman; Heinz Feldmann; Michael Gale; David Veesler; Peter Berglund; Deborah Heydenburg Fuller. 2020. "An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates." Science Translational Medicine 12, no. 555: eabc9396.

Journal article
Published: 06 July 2020 in Antiviral Research
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Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus found throughout Eastern Europe, Africa, the Middle East and Asia. It is spread through bites from infected ticks, animal husbandry and can also be acquired in the healthcare setting during care of infected patients. In humans, CCHFV can cause a sudden onset of a non-specific febrile illness that can rapidly progress to severe hemorrhagic manifestations. Currently, there is no widely available vaccine and although ribavirin has been suggested for the treatment of CCHFV, clinical efficacy in both animal models and humans is inconsistent suggesting more potent antivirals are needed for CCHFV. Favipiravir is approved in Japan for the treatment of influenza virus infections and has shown promise against other highly pathogenic RNA viruses including CCHFV with demonstrated efficacy in the type I interferon deficient mouse model. In this report we utilized the cynomolgus macaque model to evaluate the efficacy of once- and twice-daily favipiravir treatment against CCHFV infection. We found that favipiravir treatment suppressed viremia and viral shedding when treatment was initiated 24 h post-infection and viral burdens in key tissues trended lower in favipiravir-treated animals. Our data indicate that favipiravir has efficacy against CCHFV in vivo in a non-human primate model of infection.

ACS Style

David W. Hawman; Elaine Haddock; Kimberly Meade-White; Glenn Nardone; Friederike Feldmann; Patrick W. Hanley; Jamie Lovaglio; Dana Scott; Takashi Komeno; Nozomi Nakajima; Yousuke Furuta; Brian B. Gowen; Heinz Feldmann. Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques. Antiviral Research 2020, 181, 104858 .

AMA Style

David W. Hawman, Elaine Haddock, Kimberly Meade-White, Glenn Nardone, Friederike Feldmann, Patrick W. Hanley, Jamie Lovaglio, Dana Scott, Takashi Komeno, Nozomi Nakajima, Yousuke Furuta, Brian B. Gowen, Heinz Feldmann. Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques. Antiviral Research. 2020; 181 ():104858.

Chicago/Turabian Style

David W. Hawman; Elaine Haddock; Kimberly Meade-White; Glenn Nardone; Friederike Feldmann; Patrick W. Hanley; Jamie Lovaglio; Dana Scott; Takashi Komeno; Nozomi Nakajima; Yousuke Furuta; Brian B. Gowen; Heinz Feldmann. 2020. "Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques." Antiviral Research 181, no. : 104858.

Preprint content
Published: 28 May 2020
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The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.

ACS Style

Jesse H. Erasmus; Amit P. Khandhar; Alexandra C. Walls; Emily A. Hemann; Megan A. O’Connor; Patience Murapa; Jacob Archer; Shanna Leventhal; Jim Fuller; Thomas Lewis; Kevin E. Draves; Samantha Randall; Kathryn A. Guerriero; Malcolm S. Duthie; Darrick Carter; Steven G. Reed; David W. Hawman; Heinz Feldmann; Michael Gale; David Veesler; Peter Berglund; Deborah Heydenburg Fuller. Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates. 2020, 1 .

AMA Style

Jesse H. Erasmus, Amit P. Khandhar, Alexandra C. Walls, Emily A. Hemann, Megan A. O’Connor, Patience Murapa, Jacob Archer, Shanna Leventhal, Jim Fuller, Thomas Lewis, Kevin E. Draves, Samantha Randall, Kathryn A. Guerriero, Malcolm S. Duthie, Darrick Carter, Steven G. Reed, David W. Hawman, Heinz Feldmann, Michael Gale, David Veesler, Peter Berglund, Deborah Heydenburg Fuller. Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates. . 2020; ():1.

Chicago/Turabian Style

Jesse H. Erasmus; Amit P. Khandhar; Alexandra C. Walls; Emily A. Hemann; Megan A. O’Connor; Patience Murapa; Jacob Archer; Shanna Leventhal; Jim Fuller; Thomas Lewis; Kevin E. Draves; Samantha Randall; Kathryn A. Guerriero; Malcolm S. Duthie; Darrick Carter; Steven G. Reed; David W. Hawman; Heinz Feldmann; Michael Gale; David Veesler; Peter Berglund; Deborah Heydenburg Fuller. 2020. "Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates." , no. : 1.

Review
Published: 29 October 2018 in F1000Research
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Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.

ACS Style

David W. Hawman; Heinz Feldmann. Recent advances in understanding Crimean–Congo hemorrhagic fever virus. F1000Research 2018, 7, 1715 .

AMA Style

David W. Hawman, Heinz Feldmann. Recent advances in understanding Crimean–Congo hemorrhagic fever virus. F1000Research. 2018; 7 ():1715.

Chicago/Turabian Style

David W. Hawman; Heinz Feldmann. 2018. "Recent advances in understanding Crimean–Congo hemorrhagic fever virus." F1000Research 7, no. : 1715.

Journal article
Published: 01 September 2018 in Antiviral Research
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Crimean-Congo hemorrhagic fever virus (CCHFV) is a cause of serious hemorrhagic disease in humans. Humans infected with CCHFV develop a non-specific febrile illness and then progress to the hemorrhagic phase where case fatality rates can be as high as 30%. Currently there is lack of vaccines and the recommended antiviral treatment, ribavirin, has inconsistent efficacy in both human and animal studies. In this study we developed a model of CCHFV infection in type I interferon deficient mice using the clinical CCHFV isolate strain Hoti. Mice infected with strain Hoti develop a progressively worsening and ultimately fatal disease. We utilized this model along with our established model using the prototypical CCHFV strain 10200 to evaluate treatment with ribavirin or the antiviral favipiravir. While ribavirin treatment was able to suppress viral loads at early time points it was ultimately unable to prevent development of terminal disease in mice infected with either strain of CCHFV. In contrast, favipiravir showed clinical benefit even when administered late in the clinical progression of CCHFV. Interestingly, in a small subset of mice, late-onset of CCHFV was observed after favipiravir treatment was stopped and persistence of viral RNA in favipiravir treated survivors was also seen. Nevertheless, favipiravir showed significant clinical benefit against two distinct strains of CCHFV suggesting it may be a potent antiviral for treatment of human CCHFV infections.

ACS Style

David W. Hawman; Elaine Haddock; Kimberly Meade-White; Brandi Williamson; Patrick W. Hanley; Kyle Rosenke; Takashi Komeno; Yousuke Furuta; Brian B. Gowen; Heinz Feldmann. Favipiravir (T-705) but not ribavirin is effective against two distinct strains of Crimean-Congo hemorrhagic fever virus in mice. Antiviral Research 2018, 157, 18 -26.

AMA Style

David W. Hawman, Elaine Haddock, Kimberly Meade-White, Brandi Williamson, Patrick W. Hanley, Kyle Rosenke, Takashi Komeno, Yousuke Furuta, Brian B. Gowen, Heinz Feldmann. Favipiravir (T-705) but not ribavirin is effective against two distinct strains of Crimean-Congo hemorrhagic fever virus in mice. Antiviral Research. 2018; 157 ():18-26.

Chicago/Turabian Style

David W. Hawman; Elaine Haddock; Kimberly Meade-White; Brandi Williamson; Patrick W. Hanley; Kyle Rosenke; Takashi Komeno; Yousuke Furuta; Brian B. Gowen; Heinz Feldmann. 2018. "Favipiravir (T-705) but not ribavirin is effective against two distinct strains of Crimean-Congo hemorrhagic fever virus in mice." Antiviral Research 157, no. : 18-26.