This page has only limited features, please log in for full access.
Patients with severe COVID-19 often have decreased numbers of T cells, a cell type important in fighting most viral infections. However, it is not known whether the loss of T cells contributes to severe COVID-19 or is a consequence of it.
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 J. 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. mBio 2021, e0150321 .
AMA StyleKim 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 J. 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. mBio. 2021; ():e0150321.
Chicago/Turabian StyleKim 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 J. 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." mBio , no. : e0150321.
Stephan Becker; Heinz Feldmann; Jürgen A. Richt. Obituary: Professor Dr. Hans-Dieter Klenk (1938 – 2021). Emerging Microbes & Infections 2021, 10, 1 -3.
AMA StyleStephan Becker, Heinz Feldmann, Jürgen A. Richt. Obituary: Professor Dr. Hans-Dieter Klenk (1938 – 2021). Emerging Microbes & Infections. 2021; 10 (1):1-3.
Chicago/Turabian StyleStephan Becker; Heinz Feldmann; Jürgen A. Richt. 2021. "Obituary: Professor Dr. Hans-Dieter Klenk (1938 – 2021)." Emerging Microbes & Infections 10, no. 1: 1-3.
Ebola virus (EBOV) is the cause of sporadic outbreaks of human hemorrhagic disease in Africa, and the best-characterized virus in the filovirus family. The West African epidemic accelerated the clinical development of vaccines and therapeutics, leading to licensure of vaccines and antibody-based therapeutics for human use in recent years. The most widely used vaccine is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) (VSV-EBOV). Due to its favorable immune cell targeting, this vaccine has also been used as a base vector for the development of second generation VSV-based vaccines against Influenza, Nipah, and Zika viruses. However, in these situations, it may be beneficial if the immunogenicity against EBOV GP is minimized to induce a better protective immune response against the other foreign immunogen. Here, we analyzed if EBOV GP can be truncated to be less immunogenic, yet still able to drive replication of the vaccine vector. We found that the EBOV GP glycan cap and the mucin-like domain are both dispensable for VSV-EBOV replication. The glycan cap, however, appears critical for mediating a protective immune response against lethal EBOV challenge in mice.
Bharti Bhatia; Wakako Furuyama; Thomas Hoenen; Heinz Feldmann; Andrea Marzi. Ebola Virus Glycoprotein Domains Associated with Protective Efficacy. Vaccines 2021, 9, 630 .
AMA StyleBharti Bhatia, Wakako Furuyama, Thomas Hoenen, Heinz Feldmann, Andrea Marzi. Ebola Virus Glycoprotein Domains Associated with Protective Efficacy. Vaccines. 2021; 9 (6):630.
Chicago/Turabian StyleBharti Bhatia; Wakako Furuyama; Thomas Hoenen; Heinz Feldmann; Andrea Marzi. 2021. "Ebola Virus Glycoprotein Domains Associated with Protective Efficacy." Vaccines 9, no. 6: 630.
The burden on diagnostic and research laboratories to provide reliable inactivation for biological specimens to allow for safe downstream processing is high during the coronavirus disease 2019 (COVID-19) pandemic. We provide safety data regarding commonly used chemical and physical inactivation procedures that verify their effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Elaine Haddock; Friederike Feldmann; W. Lesley Shupert; Heinz Feldmann. Inactivation of SARS-CoV-2 Laboratory Specimens. The American Journal of Tropical Medicine and Hygiene 2021, 104, 2195 -2198.
AMA StyleElaine Haddock, Friederike Feldmann, W. Lesley Shupert, Heinz Feldmann. Inactivation of SARS-CoV-2 Laboratory Specimens. The American Journal of Tropical Medicine and Hygiene. 2021; 104 (6):2195-2198.
Chicago/Turabian StyleElaine Haddock; Friederike Feldmann; W. Lesley Shupert; Heinz Feldmann. 2021. "Inactivation of SARS-CoV-2 Laboratory Specimens." The American Journal of Tropical Medicine and Hygiene 104, no. 6: 2195-2198.
Zika virus (ZIKV), a member of the Flaviviridae family, is an important human pathogen that has caused epidemics in Africa, Southeast Asia, and the Americas. No licensed treatments for ZIKV disease are currently available. Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and ribavirin (1-(β-D-Ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide) are nucleoside analogs that have exhibited antiviral activity against a broad spectrum of RNA viruses, including some flaviviruses. In this study, we strengthened evidence for favipiravir and ribavirin inhibition of ZIKV replication in vitro. Testing in IFNAR−/− mice revealed that daily treatments of favipiravir were sufficient to provide protection against lethal ZIKV challenge in a dose-dependent manner but did not completely abrogate disease. Ribavirin, on the other hand, had no beneficial effect against ZIKV infection in this model and under the conditions examined. Combined treatment of ribavirin and favipiravir did not show improved outcomes over ribavirin alone. Surprisingly, outcome of favipiravir treatment was sex-dependent, with 87% of female but only 25% of male mice surviving lethal ZIKV infection. Since virus mutations were not associated with outcome, a sex-specific host response likely explains the observed sex difference.
Keesha Matz; Jackson Emanuel; Julie Callison; Don Gardner; Rebecca Rosenke; Reinaldo Mercado-Hernandez; Brandi Williamson; Heinz Feldmann; Andrea Marzi. Favipiravir (T-705) Protects IFNAR−/− Mice against Lethal Zika Virus Infection in a Sex-Dependent Manner. Microorganisms 2021, 9, 1178 .
AMA StyleKeesha Matz, Jackson Emanuel, Julie Callison, Don Gardner, Rebecca Rosenke, Reinaldo Mercado-Hernandez, Brandi Williamson, Heinz Feldmann, Andrea Marzi. Favipiravir (T-705) Protects IFNAR−/− Mice against Lethal Zika Virus Infection in a Sex-Dependent Manner. Microorganisms. 2021; 9 (6):1178.
Chicago/Turabian StyleKeesha Matz; Jackson Emanuel; Julie Callison; Don Gardner; Rebecca Rosenke; Reinaldo Mercado-Hernandez; Brandi Williamson; Heinz Feldmann; Andrea Marzi. 2021. "Favipiravir (T-705) Protects IFNAR−/− Mice against Lethal Zika Virus Infection in a Sex-Dependent Manner." Microorganisms 9, no. 6: 1178.
Hantavirus pulmonary syndrome (HPS) is an often-fatal disease caused by New World hantaviruses, such as Sin Nombre orthohantavirus (SNV). In the US, >800 cases of HPS have been confirmed since it was first discovered in 1993, of which 43 were reported from the state of Montana. The primary cause of HPS in the US is SNV, which is primarily found in the reservoir host Peromyscus maniculatus (deer mouse). The reservoir host covers most of the US, including Montana, where multiple studies found SNV in local deer mouse populations. This study aimed to check the prevalence of SNV in the deer mice at popular recreation sites throughout the Bitterroot Valley in Western Montana as compared to previous studies in western Montana. We found high prevalence (up to 20%) of deer mice positive for SNV RNA in the lungs. We were unable to obtain a SNV tissue culture isolate from the lungs but could passage SNV from lung tissue into naïve deer mice. Our findings demonstrate continuing circulation of SNV in western Montana.
Brandi Williamson; Kimberly Meade-White; Kristin Boardman; Jonathan Schulz; Carson Telford; Dania Figueroa Acosta; Trenton Bushmaker; Robert Fischer; Kyle Rosenke; Heinz Feldmann. Continuing Orthohantavirus Circulation in Deer Mice in Western Montana. Viruses 2021, 13, 1006 .
AMA StyleBrandi Williamson, Kimberly Meade-White, Kristin Boardman, Jonathan Schulz, Carson Telford, Dania Figueroa Acosta, Trenton Bushmaker, Robert Fischer, Kyle Rosenke, Heinz Feldmann. Continuing Orthohantavirus Circulation in Deer Mice in Western Montana. Viruses. 2021; 13 (6):1006.
Chicago/Turabian StyleBrandi Williamson; Kimberly Meade-White; Kristin Boardman; Jonathan Schulz; Carson Telford; Dania Figueroa Acosta; Trenton Bushmaker; Robert Fischer; Kyle Rosenke; Heinz Feldmann. 2021. "Continuing Orthohantavirus Circulation in Deer Mice in Western Montana." Viruses 13, no. 6: 1006.
Complete blood count, serum chemistry values, and biological reference intervals were compared between two age groups (34–49 and 84–120 days old) of healthy male and female laboratory raised natal multimammate mice ( Mastomys natalensis). Blood was collected via cardiocentesis under isoflurane anesthesia. Data sets of machine automated complete blood counts and clinical chemistries were analyzed. Significant differences between sex and age groups of the data sets were defined. The baseline hematologic and serum biochemistry values described here can improve interpretation of laboratory research using natal multimammate mice.
Brian J Smith; Patrick W Hanley; Ousmane Maiga; Maarit N Culbert; Marissa J Woods; Kathleen Cordova; Chad Clancy; David Safronetz; Heinrich Feldmann; Kyle Rosenke; Tsing-Lee Tang-Huau. Hematologic and serum biochemistry reference intervals using defined ASCVP methodology for laboratory natal multimammate mice (Mastomys natalensis). Laboratory Animals 2021, 1 .
AMA StyleBrian J Smith, Patrick W Hanley, Ousmane Maiga, Maarit N Culbert, Marissa J Woods, Kathleen Cordova, Chad Clancy, David Safronetz, Heinrich Feldmann, Kyle Rosenke, Tsing-Lee Tang-Huau. Hematologic and serum biochemistry reference intervals using defined ASCVP methodology for laboratory natal multimammate mice (Mastomys natalensis). Laboratory Animals. 2021; ():1.
Chicago/Turabian StyleBrian J Smith; Patrick W Hanley; Ousmane Maiga; Maarit N Culbert; Marissa J Woods; Kathleen Cordova; Chad Clancy; David Safronetz; Heinrich Feldmann; Kyle Rosenke; Tsing-Lee Tang-Huau. 2021. "Hematologic and serum biochemistry reference intervals using defined ASCVP methodology for laboratory natal multimammate mice (Mastomys natalensis)." Laboratory Animals , no. : 1.
Nipah virus (NiV) is a highly pathogenic zoonotic virus with a broad species tropism, originating in pteropid bats. Human outbreaks of NiV disease occur almost annually, often with high case-fatality rates. The specific events that lead to pathogenesis are not well defined, but the disease has both respiratory and encephalitic components, with relapsing encephalitis occurring in some cases more than a year after initial infection. Several cell types are targets of NiV, dictated by the expression of the ephrin-B2/3 ligand on the cell’s outer membrane, which interact with the NiV surface proteins. Vascular endothelial cells (ECs) are major targets of infection. Cytopathic effects (CPE), characterized by syncytia formation and cell death, and an ensuing vasculitis, are a major feature of the disease. Smooth muscle cells (SMCs) of the tunica media that line small blood vessels are infected in humans and animal models of NiV disease, although pathology or histologic changes associated with antigen-positive SMCs have not been reported. To gain an understanding of the possible contributions that SMCs might have in the development of NiV disease, we investigated the susceptibility and potential cytopathogenic changes of human SMCs to NiV infection in vitro. SMCs were permissive for NiV infection and resulted in high titers and prolonged NiV production, despite a lack of cytopathogenicity, and in the absence of detectable ephrin-B2/3. These results indicate that SMC might be important contributors to disease by producing progeny NiV during an infection, without suffering cytopathogenic consequences.
Blair DeBuysscher; Dana Scott; Rebecca Rosenke; Victoria Wahl; Heinz Feldmann; Joseph Prescott. Nipah Virus Efficiently Replicates in Human Smooth Muscle Cells without Cytopathic Effect. Cells 2021, 10, 1319 .
AMA StyleBlair DeBuysscher, Dana Scott, Rebecca Rosenke, Victoria Wahl, Heinz Feldmann, Joseph Prescott. Nipah Virus Efficiently Replicates in Human Smooth Muscle Cells without Cytopathic Effect. Cells. 2021; 10 (6):1319.
Chicago/Turabian StyleBlair DeBuysscher; Dana Scott; Rebecca Rosenke; Victoria Wahl; Heinz Feldmann; Joseph Prescott. 2021. "Nipah Virus Efficiently Replicates in Human Smooth Muscle Cells without Cytopathic Effect." Cells 10, no. 6: 1319.
Emerging coronaviruses from zoonotic reservoirs including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with human-to-human transmission and significant morbidity and mortality. Here we study both intradermal (ID) and intramuscular (IM) two-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV Spike (S) protein, which induced potent binding and neutralizing antibodies, as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared to controls. ID vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.
Ami Patel; Emma L. Reuschel; Ziyang Xu; Faraz I. Zaidi; Kevin Y. Kim; Dana P. Scott; Janess Mendoza; Stephanie Ramos; Regina Stoltz; Friederike Feldmann; Atsushi Okumura; Kimberly Meade-White; Elaine Haddock; Tina Thomas; Rebecca Rosenke; Jamie Lovaglio; Patrick W. Hanley; Greg Saturday; Kar Muthumani; Heinz Feldmann; Laurent M. Humeau; Kate E. Broderick; David B. Weiner. Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus. JCI Insight 2021, 6, 1 .
AMA StyleAmi Patel, Emma L. Reuschel, Ziyang Xu, Faraz I. Zaidi, Kevin Y. Kim, Dana P. Scott, Janess Mendoza, Stephanie Ramos, Regina Stoltz, Friederike Feldmann, Atsushi Okumura, Kimberly Meade-White, Elaine Haddock, Tina Thomas, Rebecca Rosenke, Jamie Lovaglio, Patrick W. Hanley, Greg Saturday, Kar Muthumani, Heinz Feldmann, Laurent M. Humeau, Kate E. Broderick, David B. Weiner. Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus. JCI Insight. 2021; 6 (10):1.
Chicago/Turabian StyleAmi Patel; Emma L. Reuschel; Ziyang Xu; Faraz I. Zaidi; Kevin Y. Kim; Dana P. Scott; Janess Mendoza; Stephanie Ramos; Regina Stoltz; Friederike Feldmann; Atsushi Okumura; Kimberly Meade-White; Elaine Haddock; Tina Thomas; Rebecca Rosenke; Jamie Lovaglio; Patrick W. Hanley; Greg Saturday; Kar Muthumani; Heinz Feldmann; Laurent M. Humeau; Kate E. Broderick; David B. Weiner. 2021. "Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus." JCI Insight 6, no. 10: 1.
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.
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 StyleShanna 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 StyleShanna 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.
The multimammate mouse (Mastomys natalensis; M. natalensis) has been identified as a major reservoir for multiple human pathogens including Lassa virus (LASV), Leishmania spp., Yersinia spp., and Borrelia spp. Although M. natalensis are related to well-characterized mouse and rat species commonly used in laboratory models, there is an absence of established assays and reagents to study the host immune responses of M. natalensis. As a result, there are major limitations to our understanding of immunopathology and mechanisms of immunological pathogen control in this increasingly important rodent species. In the current study, a large panel of commercially available rodent reagents were screened to identify their cross-reactivity with M. natalensis. Using these reagents, ex vivo assays were established and optimized to evaluate lymphocyte proliferation and cytokine production by M. natalensis lymphocytes. In contrast to C57BL/6J mice, lymphocytes from M. natalensis were relatively non-responsive to common stimuli such as phytohaemagglutinin P and lipopolysaccharide. However, they readily responded to concanavalin A stimulation as indicated by proliferation and cytokine production. In summary, we describe lymphoproliferative and cytokine assays demonstrating that the cellular immune responses in M. natalensis to commonly used mitogens differ from a laboratory-bred mouse strain.
Tsing-Lee Tang-Huau; Kyle Rosenke; Kimberly Meade-White; Aaron Carmody; Brian Smith; Catharine Bosio; Michael Jarvis; Heinz Feldmann. Mastomys natalensis Has a Cellular Immune Response Profile Distinct from Laboratory Mice. Viruses 2021, 13, 729 .
AMA StyleTsing-Lee Tang-Huau, Kyle Rosenke, Kimberly Meade-White, Aaron Carmody, Brian Smith, Catharine Bosio, Michael Jarvis, Heinz Feldmann. Mastomys natalensis Has a Cellular Immune Response Profile Distinct from Laboratory Mice. Viruses. 2021; 13 (5):729.
Chicago/Turabian StyleTsing-Lee Tang-Huau; Kyle Rosenke; Kimberly Meade-White; Aaron Carmody; Brian Smith; Catharine Bosio; Michael Jarvis; Heinz Feldmann. 2021. "Mastomys natalensis Has a Cellular Immune Response Profile Distinct from Laboratory Mice." Viruses 13, no. 5: 729.
The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.
Kyle Rosenke; Frederick Hansen; Benjamin Schwarz; Friederike Feldmann; Elaine Haddock; Rebecca Rosenke; Kent Barbian; Kimberly Meade-White; Atsushi Okumura; Shanna Leventhal; David W. Hawman; Emily Ricotta; Catharine M. Bosio; Craig Martens; Greg Saturday; Heinz Feldmann; Michael A. Jarvis. Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model. Nature Communications 2021, 12, 1 -8.
AMA StyleKyle Rosenke, Frederick Hansen, Benjamin Schwarz, Friederike Feldmann, Elaine Haddock, Rebecca Rosenke, Kent Barbian, Kimberly Meade-White, Atsushi Okumura, Shanna Leventhal, David W. Hawman, Emily Ricotta, Catharine M. Bosio, Craig Martens, Greg Saturday, Heinz Feldmann, Michael A. Jarvis. Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model. Nature Communications. 2021; 12 (1):1-8.
Chicago/Turabian StyleKyle Rosenke; Frederick Hansen; Benjamin Schwarz; Friederike Feldmann; Elaine Haddock; Rebecca Rosenke; Kent Barbian; Kimberly Meade-White; Atsushi Okumura; Shanna Leventhal; David W. Hawman; Emily Ricotta; Catharine M. Bosio; Craig Martens; Greg Saturday; Heinz Feldmann; Michael A. Jarvis. 2021. "Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model." Nature Communications 12, no. 1: 1-8.
Lassa fever causes an approximate 5000 to 10,000 deaths annually in West Africa and cases have been imported into Europe and the Americas, challenging public health. Although Lassa virus was first described over 5 decades ago in 1969, no treatments or vaccines have been approved to treat or prevent infection. In this review, we discuss current therapeutics in the development pipeline for the treatment of Lassa fever, focusing on those that have been evaluated in humans or animal models. Several treatments, including the antiviral favipiravir and a human monoclonal antibody cocktail, have shown efficacy in preclinical rodent and non-human primate animal models and have potential for use in clinical settings. Movement of the promising preclinical treatment options for Lassa fever into clinical trials is critical to continue addressing this neglected tropical disease.
Frederick Hansen; Michael Jarvis; Heinz Feldmann; Kyle Rosenke. Lassa Virus Treatment Options. Microorganisms 2021, 9, 772 .
AMA StyleFrederick Hansen, Michael Jarvis, Heinz Feldmann, Kyle Rosenke. Lassa Virus Treatment Options. Microorganisms. 2021; 9 (4):772.
Chicago/Turabian StyleFrederick Hansen; Michael Jarvis; Heinz Feldmann; Kyle Rosenke. 2021. "Lassa Virus Treatment Options." Microorganisms 9, no. 4: 772.
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.
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 StyleKim 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 StyleKim 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.
Summary The deployment of a vaccine that limits transmission and disease likely will be required to end the coronavirus disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S [chimpanzee adenovirus-severe acute respiratory syndrome-coronavirus-2-S]) in the upper and lower respiratory tracts of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged 1 month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induces neutralizing antibodies and T cell responses and limits or prevents infection in the upper and lower respiratory tracts after SARS-CoV-2 challenge. As ChAd-SARS-CoV-2-S confers protection in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.
Ahmed O. Hassan; Friederike Feldmann; Haiyan Zhao; David T. Curiel; Atsushi Okumura; Tsing-Lee Tang-Huau; James Brett Case; Kimberly Meade-White; Julie Callison; Rita E. Chen; Jamie Lovaglio; Patrick W. Hanley; Dana P. Scott; Daved H. Fremont; Heinz Feldmann; Michael S. Diamond. A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. Cell Reports Medicine 2021, 2, 100230 .
AMA StyleAhmed O. Hassan, Friederike Feldmann, Haiyan Zhao, David T. Curiel, Atsushi Okumura, Tsing-Lee Tang-Huau, James Brett Case, Kimberly Meade-White, Julie Callison, Rita E. Chen, Jamie Lovaglio, Patrick W. Hanley, Dana P. Scott, Daved H. Fremont, Heinz Feldmann, Michael S. Diamond. A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. Cell Reports Medicine. 2021; 2 (4):100230.
Chicago/Turabian StyleAhmed O. Hassan; Friederike Feldmann; Haiyan Zhao; David T. Curiel; Atsushi Okumura; Tsing-Lee Tang-Huau; James Brett Case; Kimberly Meade-White; Julie Callison; Rita E. Chen; Jamie Lovaglio; Patrick W. Hanley; Dana P. Scott; Daved H. Fremont; Heinz Feldmann; Michael S. Diamond. 2021. "A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques." Cell Reports Medicine 2, no. 4: 100230.
Introduction. The consistent emergence and re-emergence of ebolaviruses into a world that previously lacked an approved pharmaceutical intervention parallels an experience repeatedly played-out for most other emerging pathogenic zoonotic viruses. Investment to preemptively develop effective and low-cost prophylactic and therapeutic interventions against viruses that have high potential for emergence and societal impact should be a priority. Areas covered. Candidate drugs can be characterized into those that interfere with cellular processes required for ebola virus (EBOV) replication (host-directed), and those that directly target virally encoded functions (direct-acting). We discuss strategies to identify pharmaceutical interventions for EBOV infections. PubMed/Web of Science databases were searched to establish a detailed catalogue of these interventions. Expert opinion. Many drug candidates show promising in vitro inhibitory activity, but experience with EBOV shows the general lack of translation to in vivo efficacy for host-directed repurposed drugs. Better translation is seen for direct-acting antivirals, in particular monoclonal antibodies. The FDA-approved monoclonal antibody treatment, Inmazeb™ is a success story that could be improved in terms of impact on EBOV-associated disease and mortality, possibly by combination with other direct-acting agents targeting distinct aspects of the viral replication cycle. Costs need to be addressed given EBOV emergence primarily in under-resourced countries.
Frederick Hansen; Heinz Feldmann; Michael A Jarvis. Targeting Ebola virus replication through pharmaceutical intervention. Expert Opinion on Investigational Drugs 2021, 30, 201 -226.
AMA StyleFrederick Hansen, Heinz Feldmann, Michael A Jarvis. Targeting Ebola virus replication through pharmaceutical intervention. Expert Opinion on Investigational Drugs. 2021; 30 (3):201-226.
Chicago/Turabian StyleFrederick Hansen; Heinz Feldmann; Michael A Jarvis. 2021. "Targeting Ebola virus replication through pharmaceutical intervention." Expert Opinion on Investigational Drugs 30, no. 3: 201-226.
Background: The 2014–2016 Ebola outbreak in West Africa recapitulated that nosocomial spread of Ebola virus could occur and that health care workers were at particular risk including notable cases in Europe and North America. These instances highlighted the need for centers to better prepare for potential Ebola virus cases; including understanding how the virus spreads and which interventions pose the greatest risk. Methods: We created a fully equipped intensive care unit (ICU), within a Biosafety Level 4 (BSL4) laboratory, and infected multiple sedated non-human primates (NHPs) with Ebola virus. While providing bedside care, we sampled blood, urine, and gastric residuals; as well as buccal, ocular, nasal, rectal, and skin swabs, to assess the risks associated with routine care. We also assessed the physical environment at end-point. Results: Although viral RNA was detectable in blood as early as three days post-infection, it was not detectable in the urine, gastric fluid, or swabs until late-stage disease. While droplet spread and fomite contamination were present on a few of the surfaces that were routinely touched while providing care in the ICU for the infected animal, these may have been abrogated through good routine hygiene practices. Conclusions: Overall this study has helped further our understanding of which procedures may pose the highest risk to healthcare providers and provides temporal evidence of this over the clinical course of disease.
Mia Biondi; Lauren Garnett; Alexander Bello; Duane Funk; Philippe Poliquin; Shane Jones; Kevin Tierney; Kaylie Tran; Robert Kozak; Anders Leung; Allen Grolla; Cory Nakamura; Geoff Soule; Charlene Ranadheera; Mable Hagan; Amrinder Dhaliwal; Darwyn Kobasa; Darryl Falzarano; Hugues Bovendo; Heinz Feldmann; Murray Kesselman; Gregory Hansen; Jason Gren; Todd Mortimer; Trina Racine; Yvon Deschambault; Jocelyn Edmonds; Sam Aminian; Ray Saurette; Mark Allan; Lauren Rondeau; John Huynh; Sharron Hadder; Christy Press; Christine DeGraff; Stephanie Kucas; Julie Kubay; Kim Azanarsky; Bradley Cook; Bj Hancock; Anand Kumar; Reeni Soni; Daryl Schantz; Jarrid McKitrick; Bryce Warner; Bryan Griffin; Xiangguo Qiu; Gary Kobinger; Dave Safronetz; Heidi Wood; Derek Stein; Todd Cutts; Brad Pickering; James Kenny; Steven Theriault; Liam Menec; Robert Vendramelli; Sean Higgins; Logan Banadyga; Guodong Liu; Niaz Rahim; Samantha Kasloff; Angela Sloan; Shihua He; Nikesh Tailor; Alixandra Albietz; Gary Wong; Michael Gray; Friederike Feldmann; Andrea Marzi; George Risi; James Strong. Characterization of Ebola Virus Risk to Bedside Providers in an Intensive Care Environment. Microorganisms 2021, 9, 498 .
AMA StyleMia Biondi, Lauren Garnett, Alexander Bello, Duane Funk, Philippe Poliquin, Shane Jones, Kevin Tierney, Kaylie Tran, Robert Kozak, Anders Leung, Allen Grolla, Cory Nakamura, Geoff Soule, Charlene Ranadheera, Mable Hagan, Amrinder Dhaliwal, Darwyn Kobasa, Darryl Falzarano, Hugues Bovendo, Heinz Feldmann, Murray Kesselman, Gregory Hansen, Jason Gren, Todd Mortimer, Trina Racine, Yvon Deschambault, Jocelyn Edmonds, Sam Aminian, Ray Saurette, Mark Allan, Lauren Rondeau, John Huynh, Sharron Hadder, Christy Press, Christine DeGraff, Stephanie Kucas, Julie Kubay, Kim Azanarsky, Bradley Cook, Bj Hancock, Anand Kumar, Reeni Soni, Daryl Schantz, Jarrid McKitrick, Bryce Warner, Bryan Griffin, Xiangguo Qiu, Gary Kobinger, Dave Safronetz, Heidi Wood, Derek Stein, Todd Cutts, Brad Pickering, James Kenny, Steven Theriault, Liam Menec, Robert Vendramelli, Sean Higgins, Logan Banadyga, Guodong Liu, Niaz Rahim, Samantha Kasloff, Angela Sloan, Shihua He, Nikesh Tailor, Alixandra Albietz, Gary Wong, Michael Gray, Friederike Feldmann, Andrea Marzi, George Risi, James Strong. Characterization of Ebola Virus Risk to Bedside Providers in an Intensive Care Environment. Microorganisms. 2021; 9 (3):498.
Chicago/Turabian StyleMia Biondi; Lauren Garnett; Alexander Bello; Duane Funk; Philippe Poliquin; Shane Jones; Kevin Tierney; Kaylie Tran; Robert Kozak; Anders Leung; Allen Grolla; Cory Nakamura; Geoff Soule; Charlene Ranadheera; Mable Hagan; Amrinder Dhaliwal; Darwyn Kobasa; Darryl Falzarano; Hugues Bovendo; Heinz Feldmann; Murray Kesselman; Gregory Hansen; Jason Gren; Todd Mortimer; Trina Racine; Yvon Deschambault; Jocelyn Edmonds; Sam Aminian; Ray Saurette; Mark Allan; Lauren Rondeau; John Huynh; Sharron Hadder; Christy Press; Christine DeGraff; Stephanie Kucas; Julie Kubay; Kim Azanarsky; Bradley Cook; Bj Hancock; Anand Kumar; Reeni Soni; Daryl Schantz; Jarrid McKitrick; Bryce Warner; Bryan Griffin; Xiangguo Qiu; Gary Kobinger; Dave Safronetz; Heidi Wood; Derek Stein; Todd Cutts; Brad Pickering; James Kenny; Steven Theriault; Liam Menec; Robert Vendramelli; Sean Higgins; Logan Banadyga; Guodong Liu; Niaz Rahim; Samantha Kasloff; Angela Sloan; Shihua He; Nikesh Tailor; Alixandra Albietz; Gary Wong; Michael Gray; Friederike Feldmann; Andrea Marzi; George Risi; James Strong. 2021. "Characterization of Ebola Virus Risk to Bedside Providers in an Intensive Care Environment." Microorganisms 9, no. 3: 498.
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.
Shanna Leventhal; Drew Wilson; Heinz Feldmann; David Hawman. A Look into Bunyavirales Genomes: Functions of Non-Structural (NS) Proteins. Viruses 2021, 13, 314 .
AMA StyleShanna 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 StyleShanna Leventhal; Drew Wilson; Heinz Feldmann; David Hawman. 2021. "A Look into Bunyavirales Genomes: Functions of Non-Structural (NS) Proteins." Viruses 13, no. 2: 314.
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.
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 StyleDavid 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 StyleDavid 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.
SUMMARY The deployment of a vaccine that limits transmission and disease likely will be required to end the Coronavirus Disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S) in the upper and lower respiratory tract of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged one month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induced neutralizing antibodies and T cell responses and limited or prevented infection in the upper and lower respiratory tract after SARS-CoV-2 challenge. As this single intranasal dose vaccine confers protection against SARS-CoV-2 in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.
Ahmed O. Hassan; Friederike Feldmann; Haiyan Zhao; David T. Curiel; Atsushi Okumura; Tsing-Lee Tang-Huau; James Brett Case; Kimberly Meade-White; Julie Callison; Jamie Lovaglio; Patrick W. Hanley; Dana P. Scott; Daved H. Fremont; Heinz Feldmann; Michael S. Diamond. A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. 2021, 1 .
AMA StyleAhmed O. Hassan, Friederike Feldmann, Haiyan Zhao, David T. Curiel, Atsushi Okumura, Tsing-Lee Tang-Huau, James Brett Case, Kimberly Meade-White, Julie Callison, Jamie Lovaglio, Patrick W. Hanley, Dana P. Scott, Daved H. Fremont, Heinz Feldmann, Michael S. Diamond. A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. . 2021; ():1.
Chicago/Turabian StyleAhmed O. Hassan; Friederike Feldmann; Haiyan Zhao; David T. Curiel; Atsushi Okumura; Tsing-Lee Tang-Huau; James Brett Case; Kimberly Meade-White; Julie Callison; Jamie Lovaglio; Patrick W. Hanley; Dana P. Scott; Daved H. Fremont; Heinz Feldmann; Michael S. Diamond. 2021. "A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques." , no. : 1.