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  1. Article ; Online: A U.S. Government-Coordinated Effort to Leverage Non-Human Primate Data to Facilitate Ebolavirus Vaccine Development

    Kimberly L. Taylor / Lynda Lanning / Lawrence Wolfraim / Sonia Shrivastava Gales / Colleen Sico / William E. Dowling / Lucy A. Ward / William C. Florence / Edwin Nuzum / Paula R. Bryant

    Vaccines, Vol 10, Iss 1201, p

    2022  Volume 1201

    Abstract: A United States Government (USG) interagency group, the Filovirus Animal Non-Clinical Group (FANG), has been established to support the development of biodefense medical countermeasures (MCMs). As both vaccines and therapeutics are licensed using “non- ... ...

    Abstract A United States Government (USG) interagency group, the Filovirus Animal Non-Clinical Group (FANG), has been established to support the development of biodefense medical countermeasures (MCMs). As both vaccines and therapeutics are licensed using “non-traditional pathways”, such as the U.S. Food and Drug Administration’s (FDA) Animal Rule (AR), non-human primate (NHP) models and associated assays have been developed and standardized across BSL4 testing sites to evaluate candidate products. Vaccine candidates are evaluated using these NHP models, and through this public–private partnership, a meta-analysis of NHP control data has been conducted and submitted to the FDA as a master file. This is an example of how existing NHP control data can be leveraged in lieu of conducting separate natural history studies at multiple testing facilities to demonstrate the consistency of a standardized animal model for vaccine development. As a result, animal use can be minimized and the duplication of effort avoided, thus reducing the amount of time needed to conduct additional studies, as well as the cost of vaccine candidate development. This successful strategy may be applied to other pathogens of high consequence for vaccine development, and shows how strategic preparedness for biodefense can be leveraged in response to outbreaks and public health emergencies.
    Keywords vaccine development ; filovirus ; ebolavirus ; non-human primate ; public–private partnership ; regulatory ; Medicine ; R
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Retrospective Analysis of Pneumonic Tularemia in Operation Whitecoat Human Subjects

    Mark S. Williams / Marianne R. Baker / Tina Guina / Judith A. Hewitt / Lynda Lanning / Heather Hill / Jeanine M. May / Beverly Fogtman / Phillip R. Pittman

    Frontiers in Medicine, Vol

    Disease Progression and Tetracycline Efficacy

    2019  Volume 6

    Abstract: Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans. The incidence of tularemia is very low with a lack of comprehensive data that describe disease in humans due to ... ...

    Abstract Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans. The incidence of tularemia is very low with a lack of comprehensive data that describe disease in humans due to difficulty in understanding time and routes of exposure. Under the title Operation Whitecoat, researchers at Ft. Detrick, MD conducted 40 clinical studies of tularemia from 1958 to 1968. In these studies, one of the objectives was to evaluate candidate countermeasures for treatment or prophylaxis of disease after exposure to Francisella tularensis strain Schu S4 by inhalation. These studies were reviewed retrospectively to delineate the early signs and symptoms or natural history of pneumonic tularemia and examine the efficacy of tetracycline in controlled human clinical studies. Using vital signs, onset of fever was objectively defined and calculated for each subject, while Adverse Events reported after exposure were also used to define the timing of disease onset and symptoms of early disease. There was a dose response relationship between time to fever onset and exposed dose at 200 cfu (172.8 h), 700 cfu (163.2 h), 2,500 cfu (105.3 h), and 25,000 cfu (75.5 h). Onset of fever was typically the earliest sign of disease at all doses but was often accompanied by symptoms such as headache, myalgia, chest pain, and nausea, irrespective of dose except at 200 cfu where only 50% of subjects exhibited fever onset or symptoms. Examining the efficacy of different treatment regimens of tetracycline, ineffective treatments were indicated by relapse of disease (fever and Adverse Events) after cessation of antibiotic treatment. Stratification of the data suggested that treatment for <14 days or doses <2g/day was associated with increased percentage of subjects with relapse of disease symptoms. Although these types of human challenge studies would not be ethically possible now, the climate post-World War II supported human testing under rigorous conditions with informed consent. ...
    Keywords tularemia ; human ; pneumonic ; Whitecoat ; tetracycline ; Medicine (General) ; R5-920
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A mouse strain defective in both T cells and NK cells has enhanced sensitivity to tumor induction by plasmid DNA expressing both activated H-Ras and c-Myc.

    Li Sheng-Fowler / Wei Tu / Haiqing Fu / Haruhiko Murata / Lynda Lanning / Gideon Foseh / Juliete Macauley / Donald Blair / Stephen H Hughes / John M Coffin / Andrew M Lewis / Keith Peden

    PLoS ONE, Vol 9, Iss 10, p e

    2014  Volume 108926

    Abstract: As part of safety studies to evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cells, we have been developing in vivo assays to detect and quantify the oncogenic activity of DNA. We generated a plasmid expressing both an ... ...

    Abstract As part of safety studies to evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cells, we have been developing in vivo assays to detect and quantify the oncogenic activity of DNA. We generated a plasmid expressing both an activated human H-ras gene and murine c-myc gene and showed that 1 µg of this plasmid, pMSV-T24-H-ras/MSV-c-myc, was capable of inducing tumors in newborn NIH Swiss mice. However, to be able to detect the oncogenicity of dominant activated oncogenes in cellular DNA, a more sensitive system was needed. In this paper, we demonstrate that the newborn CD3 epsilon transgenic mouse, which is defective in both T-cell and NK-cell functions, can detect the oncogenic activity of 25 ng of the circular form of pMSV-T24-H-ras/MSV-c-myc. When this plasmid was inoculated as linear DNA, amounts of DNA as low as 800 pg were capable of inducing tumors. Animals were found that had multiple tumors, and these tumors were independent and likely clonal. These results demonstrate that the newborn CD3 epsilon mouse is highly sensitive for the detection of oncogenic activity of DNA. To determine whether it can detect the oncogenic activity of cellular DNA derived from four human tumor-cell lines (HeLa, A549, HT-1080, and CEM), DNA (100 µg) was inoculated into newborn CD3 epsilon mice both in the presence of 1 µg of linear pMSV-T24-H-ras/MSV-c-myc as positive control and in its absence. While tumors were induced in 100% of mice with the positive-control plasmid, no tumors were induced in mice receiving any of the tumor DNAs alone. These results demonstrate that detection of oncogenes in cellular DNA derived from four human tumor-derived cell lines in this mouse system was not possible; the results also show the importance of including a positive-control plasmid to detect inhibitory effects of the cellular DNA.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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