16 results on '"Anna Honko"'
Search Results
2. IgG-like bispecific antibodies with potent and synergistic neutralization against circulating SARS-CoV-2 variants of concern
- Author
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Matthew R. Chang, Luke Tomasovic, Natalia A. Kuzmina, Adam J. Ronk, Patrick O. Byrne, Rebecca Johnson, Nadia Storm, Eduardo Olmedillas, Yixuan J. Hou, Alexandra Schäfer, Sarah R. Leist, Longping V. Tse, Hanzhong Ke, Christian Coherd, Katrina Nguyen, Maliwan Kamkaew, Anna Honko, Quan Zhu, Galit Alter, Erica Ollmann Saphire, Jason S. McLellan, Anthony Griffiths, Ralph S. Baric, Alexander Bukreyev, and Wayne A. Marasco
- Subjects
Science - Abstract
COVID-19 can be treated with monoclonal antibodies against SARS-CoV-2, but emerging new variants might show resistance towards existing therapy. Here authors show that anti-SARS-CoV-2 spike human single-chain antibody fragments could gain neutralizing activity against variants of concern upon engineering into a human bispecific antibody.
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- 2022
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3. Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo.
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Phillip R Pittman, James W Martin, Placide Mbala Kingebeni, Jean-Jacques Muyembe Tamfum, Gaston Mwema, Qingwen Wan, Pierre Ewala, Jules Alonga, Guy Bilulu, Mary G Reynolds, Xiaofei Quinn, Sarah Norris, Michael B Townsend, Panayampalli S Satheshkumar, James Wadding, Bryony Soltis, Anna Honko, Fernando B Güereña, Lawrence Korman, Kerry Patterson, David A Schwartz, John W Huggins, and Kole Human Mpox Infection Study Group
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Soeurs Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.
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- 2023
- Full Text
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4. An introduction to the Marburg virus vaccine consortium, MARVAC
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Robert W. Cross, Ira M. Longini, Stephan Becker, Karin Bok, David Boucher, Miles W. Carroll, Janet V. Díaz, William E. Dowling, Ruxandra Draghia-Akli, James T. Duworko, John M. Dye, Michael A. Egan, Patricia Fast, Amy Finan, Courtney Finch, Thomas R. Fleming, Joan Fusco, Thomas W. Geisbert, Anthony Griffiths, Stephan Günther, Lisa E. Hensley, Anna Honko, Ruth Hunegnaw, Jocelyn Jakubik, Julie Ledgerwood, Kerstin Luhn, Demetrius Matassov, Jeffrey Meshulam, Emily V. Nelson, Christopher L. Parks, Roxana Rustomjee, David Safronetz, Lauren M. Schwartz, Dean Smith, Paul Smock, Ydrissa Sow, Christina F. Spiropoulou, Nancy J. Sullivan, Kelly L. Warfield, Daniel Wolfe, Courtney Woolsey, Roland Zahn, Ana María Henao-Restrepo, César Muñoz-Fontela, and Andrea Marzi
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The emergence of Marburg virus (MARV) in Guinea and Ghana triggered the assembly of the MARV vaccine “MARVAC” consortium representing leaders in the field of vaccine research and development aiming to facilitate a rapid response to this infectious disease threat. Here, we discuss current progress, challenges, and future directions for MARV vaccines.
- Published
- 2022
5. Detecting Pathogen Exposure During the Non-symptomatic Incubation Period Using Physiological Data: Proof of Concept in Non-human Primates
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Shakti Davis, Lauren Milechin, Tejash Patel, Mark Hernandez, Greg Ciccarelli, Siddharth Samsi, Lisa Hensley, Arthur Goff, John Trefry, Sara Johnston, Bret Purcell, Catherine Cabrera, Jack Fleischman, Albert Reuther, Kajal Claypool, Franco Rossi, Anna Honko, William Pratt, and Albert Swiston
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machine learning ,random forest ,physiological signals ,incubation period ,pre-symptomatic ,early infection detection ,Physiology ,QP1-981 - Abstract
Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First, we seek to determine the upper limits of early warning detection through physiological measurements. Second, we investigate whether the detected physiological response is specific to the pathogen. Third, we explore the feasibility of extending early warning detection with wearable devices.Research Methods: For the first objective, we developed a supervised random forest algorithm to detect pathogen exposure in the asymptomatic period prior to overt symptoms (fever). We used high-resolution physiological telemetry data (aortic blood pressure, intrathoracic pressure, electrocardiograms, and core temperature) from non-human primate animal models exposed to two viral pathogens: Ebola and Marburg (N = 20). Second, to determine reusability across different pathogens, we evaluated our algorithm against three independent physiological datasets from non-human primate models (N = 13) exposed to three different pathogens: Lassa and Nipah viruses and Y. pestis. For the third objective, we evaluated performance degradation when the algorithm was restricted to features derived from electrocardiogram (ECG) waveforms to emulate data from a non-invasive wearable device.Results: First, our cross-validated random forest classifier provides a mean early warning of 51 ± 12 h, with an area under the receiver-operating characteristic curve (AUC) of 0.93 ± 0.01. Second, our algorithm achieved comparable performance when applied to datasets from different pathogen exposures – a mean early warning of 51 ± 14 h and AUC of 0.95 ± 0.01. Last, with a degraded feature set derived solely from ECG, we observed minimal degradation – a mean early warning of 46 ± 14 h and AUC of 0.91 ± 0.001.Conclusion: Under controlled experimental conditions, physiological measurements can provide over 2 days of early warning with high AUC. Deviations in physiological signals following exposure to a pathogen are due to the underlying host’s immunological response and are not specific to the pathogen. Pre-symptomatic detection is strong even when features are limited to ECG-derivatives, suggesting that this approach may translate to non-invasive wearable devices.
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- 2021
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6. Dissecting strategies to tune the therapeutic potential of SARS-CoV-2–specific monoclonal antibody CR3022
- Author
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Caroline Atyeo, Matthew D. Slein, Stephanie Fischinger, John Burke, Alexandra Schäfer, Sarah R. Leist, Natalia A. Kuzmina, Chad Mire, Anna Honko, Rebecca Johnson, Nadia Storm, Matthew Bernett, Pei Tong, Teng Zuo, Junrui Lin, Adam Zuiani, Caitlyn Linde, Todd Suscovich, Duane R. Wesemann, Anthony Griffiths, John R. Desjarlais, Boris D. Juelg, Jaap Goudsmit, Alexander Bukreyev, Ralph Baric, and Galit Alter
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COVID-19 ,Immunology ,Medicine - Abstract
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics, has paralyzed the globe. Although significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc interactions may be vital to eliminate the virus. To explore the role of Fc activity in SARS-CoV-2 immunity, the functional potential of a cross–SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc variants, no protection was observed after administration of WT IgG1 in mice or hamsters. Conversely, the functionally enhanced Fc variant resulted in increased pathology in both the mouse and hamster models, causing weight loss in mice and enhanced viral replication and weight loss in the more susceptible hamster model, highlighting the pathological functions of Fc-enhancing mutations. These data point to the critical need for strategic Fc engineering for the treatment of SARS-CoV-2 infection.
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- 2021
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7. Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques
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Isaac Downs, Joshua C. Johnson, Franco Rossi, David Dyer, David L. Saunders, Nancy A. Twenhafel, Heather L. Esham, William D. Pratt, John Trefry, Elizabeth Zumbrun, Paul R. Facemire, Sara C. Johnston, Erin L. Tompkins, Nathan K. Jansen, Anna Honko, and Anthony P. Cardile
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Ebola ,Kikwit ,Zaire ,virus ,viral hemorrhagic fever ,natural history ,Microbiology ,QR1-502 - Abstract
Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermeasures. In this natural history study, four rhesus macaques were challenged via aerosol with a target titer of 1000 plaque-forming units per milliliter of Ebola virus. The course of disease was split into the following stages for descriptive purposes: subclinical, clinical, and decompensated. During the subclinical stage, high levels of venous partial pressure of carbon dioxide led to respiratory acidemia in three of four of the NHPs, and all developed lymphopenia. During the clinical stage, all animals had fever, viremia, and respiratory alkalosis. The decompensatory stage involved coagulopathy, cytokine storm, and liver and renal injury. These events were followed by hypotension, elevated lactate, metabolic acidemia, shock and mortality similar to historic intramuscular challenge studies. Viral loads in the lungs of aerosol-exposed animals were not distinctly different compared to previous intramuscularly challenged studies. Differences in the aerosol model, compared to intramuscular model, include an extended subclinical stage, shortened clinical stage, and general decompensated stage. Therefore, the shortened timeframe for clinical detection of the aerosol-induced disease can impair timely therapeutic administration. In summary, this nonhuman primate model of aerosol-induced EVD characterizes early disease markers and additional details to enable countermeasure development.
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- 2021
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8. Natural History of Aerosol Induced Lassa Fever in Non-Human Primates
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Isaac L. Downs, Carl I. Shaia, Xiankun Zeng, Joshua C. Johnson, Lisa Hensley, David L. Saunders, Franco Rossi, Kathleen A. Cashman, Heather L. Esham, Melissa K. Gregory, William D. Pratt, John C. Trefry, Kyle A. Everson, Charles B. Larcom, Arthur C. Okwesili, Anthony P. Cardile, and Anna Honko
- Subjects
LASV ,Lassa ,Josiah ,VHF ,telemetry ,aerosol ,Microbiology ,QR1-502 - Abstract
Lassa virus (LASV), an arenavirus causing Lassa fever, is endemic to West Africa with up to 300,000 cases and between 5000 and 10,000 deaths per year. Rarely seen in the United States, Lassa virus is a CDC category A biological agent inasmuch deliberate aerosol exposure can have high mortality rates compared to naturally acquired infection. With the need for an animal model, specific countermeasures remain elusive as there is no FDA-approved vaccine. This natural history of aerosolized Lassa virus exposure in Macaca fascicularis was studied under continuous telemetric surveillance. The macaque response to challenge was largely analogous to severe human disease with fever, tachycardia, hypotension, and tachypnea. During initial observations, an increase trend of activated monocytes positive for viral glycoprotein was accompanied by lymphocytopenia. Disease uniformly progressed to high viremia followed by low anion gap, alkalosis, anemia, and thrombocytopenia. Hypoproteinemia occurred late in infection followed by increased levels of white blood cells, cytokines, chemokines, and biochemical markers of liver injury. Viral nucleic acids were detected in tissues of three non-survivors at endpoint, but not in the lone survivor. This study provides useful details to benchmark a pivotal model of Lassa fever in support of medical countermeasure development for both endemic disease and traditional biodefense purposes.
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- 2020
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9. Critical role for cholesterol in Lassa fever virus entry identified by a novel small molecule inhibitor targeting the viral receptor LAMP1.
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May Kwang-Mei Wang, Tao Ren, Hu Liu, Sun-Young Lim, Kyungae Lee, Anna Honko, Huanying Zhou, Julie Dyall, Lisa Hensley, Ashley K Gartin, and James M Cunningham
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Lassa fever virus (LASV) is endemic in West Africa and causes severe hemorrhagic fever and sensorineural hearing loss. We identified a small molecule inhibitor of LASV and used it to analyze the mechanism of entry. Using a photo-reactive analog that retains antiviral activity as a probe, we identified the inhibitor target as lysosome-associated membrane protein 1 (LAMP1), a host factor that binds to the LASV glycoprotein (GP) during infection. We found that LAMP1 binding to LASV GP is cholesterol-dependent, and that the inhibitor blocks infection by competing with cholesterol in LAMP1. Mutational analysis of a docking-based model identified a putative inhibitor binding site in the cholesterol-binding pocket within the LAMP1 domain that binds GP. These findings identify a critical role for cholesterol in LASV entry and a potential target for therapeutic intervention.
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- 2018
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10. Ebola virus genome plasticity as a marker of its passaging history: a comparison of in vitro passaging to non-human primate infection.
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Jeffrey R Kugelman, Michael S Lee, Cynthia A Rossi, Sarah E McCarthy, Sheli R Radoshitzky, John M Dye, Lisa E Hensley, Anna Honko, Jens H Kuhn, Peter B Jahrling, Travis K Warren, Chris A Whitehouse, Sina Bavari, and Gustavo Palacios
- Subjects
Medicine ,Science - Abstract
To identify polymorphic sites that could be used as biomarkers of Ebola virus passage history, we repeatedly amplified Ebola virus (Kikwit variant) in vitro and in vivo and performed deep sequencing analysis of the complete genomes of the viral subpopulations. We then determined the sites undergoing selection during passage in Vero E6 cells. Four locations within the Ebola virus Kikwit genome were identified that together segregate cell culture-passaged virus and virus obtained from infected non-human primates. Three of the identified sites are located within the glycoprotein gene (GP) sequence: the poly-U (RNA editing) site at position 6925, as well as positions 6677, and 6179. One site was found in the VP24 gene at position 10833. In all cases, in vitro and in vivo, both populations (majority and minority variants) were maintained in the viral swarm, with rapid selections occurring after a few passages or infections. This analysis approach will be useful to differentiate whether filovirus stocks with unknown history have been passaged in cell culture and may support filovirus stock standardization for medical countermeasure development.
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- 2012
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11. Clinical characterization of human monkeypox infections in the Democratic Republic of the Congo
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Phillip R. Pittman, James W. Martin, Placide Mbala Kingebeni, Jean-Jacques Muyembe Tamfum, Qingwen Wan, Mary G. Reynolds, Xiaofei Quinn, Sarah Norris, Michael B. Townsend, Panayampalli S. Satheshkumar, Bryony Soltis, Anna Honko, Fernando B. Güereña, Lawrence Korman, and John W. Huggins
- Abstract
We describe the results of a prospective observational study of the clinical natural history of human monkeypox virus (MPXV) infections at the remote General Reference Hospital of Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Monkeypox (MPX) study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Seours Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human monkeypox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 4 of 5 (80%) patients who were pregnant at admission. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were MPX rash (99.5%) and lymphadenopathy (98.6%). Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had significantly higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia, p=0.0072); maximum lesion count (p=0.0025); day of admission mean AST and ALT (p=0.0002 and p = 0.0224, respectively, adjusted p-values).Author SummaryThis is a prospective observational study of Human monkeypox disease, an emerging infectious disease in parts of the continent of Africa. There are certain differential characteristics when compared to other pox diseases. This paper describes the presenting symptoms and signs of human monkeypox disease, laboratory findings and makes recommendation for the medical treatment of patients with monkeypox disease.
- Published
- 2022
12. Rapid and Durable Protection Against Marburg Virus with a Single-Shot ChAd3-MARV GP Vaccine
- Author
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Ruth Hunegnaw, Anna Honko, Lingshu Wang, Derick Carr, Tamar Murray, Wei Shi, Caitlyn N. M. Dulan, Kathryn E. Foulds, Krystle N. Agans, Robert W. Cross, Joan B. Geisbert, Thomas W. Geisbert, Cheng Cheng, Aurélie Ploquin, Daphne A. Stanley, Gary J. Nabel, and Nancy J. Sullivan
- Abstract
Marburg virus (MARV) causes a severe hemorrhagic fever disease in primates with mortality rates in humans up to 90%. Since 2018, MARV has been identified as a priority pathogen by the WHO, needing urgent research and development of countermeasures due to the high public health risk it poses. Recently, the first case of MARV in West Africa underscored the significant outbreak potential of this virus. The potential for cross border spread as had occurred during the Ebola 2014-2016 outbreak illustrates the critical need for Marburg vaccines. To support regulatory approval of the ChAd3-Marburg vaccine that has completed Phase I trials, we show that a non-replicating chimpanzee-derived adenovirus vector with a demonstrated safety profile in humans (ChAd3) protected against a uniformly lethal challenge with Marburg-Angola. Protective immunity was achieved within 7 days of vaccination and was maintained through one year post vaccination, antigen-specific antibodies were a significant immune correlate of protection in the acute challenge model (p=0.0003), and predictive for protection with an AUC = 0.88. These results demonstrate that a single-shot ChAd3 MARV vaccine generated a protective immune response that was both rapid and durable with a significant immune correlate of protection that will support advanced clinical development.One Sentence SummaryA single-shot of non-replicating ChAd3-MARV vaccine demonstrated both rapid (within 1 week) and durable (12 months) protection against lethal Marburg virus infection in macaques.
- Published
- 2021
13. Therapeutic Potential of SARS-CoV-2-Specific Monoclonal Antibody CR3022
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Caroline Atyeo, Matthew D. Slein, Stephanie Fischinger, John Burke, Alexandra Schӓfer, Sarah R. Leist, Anna Honko, Rebecca Johnson, Nadia Storm, Matthew Bernett, Caitlyn Linde, Todd Suscovich, Anthony Griffiths, John R. Desjarlais, Boris D. Juelg, Jaap Goudsmit, Ralph Baric, and Galit Alter
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,medicine.drug_class ,business.industry ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,fungi ,virus diseases ,macromolecular substances ,Monoclonal antibody ,Virology ,Immunity ,medicine ,skin and connective tissue diseases ,business - Abstract
The spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics or vaccines, has paralyzed the globe While
- Published
- 2020
14. Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition.
- Author
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Xiangzhao Ai, Dan Wang, Anna Honko, Yaou Duan, Gavrish, Igor, Fang, Ronnie H., Griffiths, Anthony, Weiwei Gao, and Liangfang Zhang
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- 2021
- Full Text
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15. Evaluation of the use of primate undershirts as a refinement practice for jacketed rhesus macaques (Macaca mulatta)
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Richard, Kelly, Amy, Carlson, Steven J, Kern, Amy, Field, Shannon, Marko, Emily, Bailey, Sarah, Norris, Anna, Honko, and Pedro, Rico
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Male ,Protective Clothing ,Animals, Laboratory ,Husbandry ,Animals ,Telemetry ,Female ,respiratory system ,Macaca mulatta ,humanities ,Body Temperature - Abstract
Jacketing of nonhuman primates (NHP) is a commonly used practice in the laboratory animal setting to support data collection with reduced direct human-to-animal interaction. NHP often wear jackets for several weeks, potentially leading to the formation of dermal lesions ranging from mild alopecia to severe full-thickness ulceration. We sought to evaluate the addition of a commercially available undershirt for primates as a possible refinement practice for our jacketed rhesus macaques. In this study, we compared the lesion count, location, and severity and differences in rectal body temperature between jacketed NHP with undershirts with those wearing the jackets alone. In both groups, most lesions (75%) were located at either the underarm or shoulder. The percentages of total lesions in the back and neck were lower in jacketed NHP that wore undershirts than in those that did not. In addition, the estimated odds of increased severity scores in jacketed NHP without undershirts was 1.80 times that for NHP that wore both jackets and undershirts. Both groups of NHP showed a significant decrease in dermal scores with time, indicating adaptation to the jackets with or without undershirts. However, there was no statistically significant decrease in lesion count, severity, or location in jacketed NHP that wore undershirts compared with those that did not.
- Published
- 2014
16. Evaluation of the use of primate undershirts as a refinement practice for jacketed rhesus macaques (Macaca mulatta)
- Author
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Kelly Iii, R., Carlson, A., Kern, S. J., Field, A., Marko, S., Bailey, E., Norris, S., Anna Honko, and Rico, P.
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