BSTP/STP Webinar: Respiratory System
November 10, 2020
11:00 AM EST, 4:00 PM GMT/ 5:00 PM CET
A BSTP webinar - in collaboration with the Society of Toxicological Pathology (STP) to be held on Tuesday 10th November 2020, at 11:00 am Eastern Standard Time (New York, GMT-05:00), 4:00 pm GMT Time (London, GMT), and the duration of the webinar will be up to 1 hour.
Lung pathology associated with experimental SARS-CoV-2 virus infection in rhesus macaques. Lesion scoring and differentiation from background findings
Ronnie Chamanza, BVSc, MSc, MRCVS, FRCPath, FIATP; and Marjolein van Heerden, DVM, DECVP
Nonclinical Safety, Janssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium
Knowledge and understanding of the morphologic patterns of lung pathology provides key insight into the possible etiological agent, route of exposure, pathogenesis of the lesions, effect on pulmonary function, and the sequela and complications. The SARS-CoV-2 is a novel betacoronavirus and causal agent of the disease COVID-19, which causes severe lung disease in humans. Among the preclinical animal models used in immunogenicity trials and efficacy studies for vaccine development is the nonhuman primate (NHP) model. Histopathology evaluation and interpretation of virus inoculation-induced lung lesions, and differentiating them from incidental or pre-existing background lesions are key to determining the efficacy of any vaccine regimen. In addition, the ability to detect any possible evidence of antibody dependent disease enhancement (ADE) in vaccinated animals requires a careful characterization and documentation of the SARS-CoV-2 -induced lesions in the particular animal species and age group during model development, as well as the development of a detailed and robust lung lesion scoring system. This lecture presents cases that outline the predominant lung histopathological lesions and morphologic patterns associated with experimental SARS-CoV-2 virus inoculation in juvenile, adult and elderly rhesus macaques from various geographical regions, and the differentiation of virus-induced findings from background and incidental (including procedural) lesions. Examples of a lung lesion scoring system and merits and demerits of blinded evaluation of the lungs are also presented.
The Challenges of Inhaled Biologics
(Anthony) Peter Hall, BSc, BVSc, MRCVS, PhD, FRCPath
UCB Pharma Ltd, United Kingdom
The inhalation route is a relatively novel drug delivery route for biotherapeutics and, as a result, there is a paucity of published data and experience within the toxicology/pathology community. In recent years, findings arising in toxicology studies with inhaled biologics have provoked concern and regulatory challenges due, in part, to the lack of understanding of the expected pathology, mechanisms and adversity induced by this mode of delivery. In this manuscript the authors describe 12 case studies, comprising 18 toxicology studies, using a range of inhaled biotherapeutics (monoclonal antibodies, fragment antigen-binding antibodies, domain antibodies, therapeutic proteins/peptides and oligonucleotides) in rodents, non-human primates (NHPs) and the rabbit in subacute (1-week) to chronic (26-week) toxicology studies. Analysis of the data revealed that many of these molecules were associated with a characteristic pattern of toxicity with high levels of immunogenicity characterised principally by perivascular/peribronchiolar (PV/PB) mononuclear inflammatory cell (MIC) infiltrates and terminal airway/alveolar inflammatory cell infiltrates ranging from simple (‘uncomplicated’) increases in macrophages through to mixed inflammatory cell infiltration and inflammation. The PV/PB MIC changes were considered most likely secondary to immunogenicity whereas simple increases in alveolar macrophages were most likely secondary to clearance mechanisms. Alveolar inflammatory cell infiltrates and inflammation were thought likely induced by immunostimulation through pharmacologic modulation of target biology or type III hypersensitivity (immune complex disease).Finally, a group of experts provide introductory thoughts regarding the adversity of inhaled biotheraputics and the basis for reasonable differences of opinion that might arise between toxicologists, pathologists and regulators.
We look forward to your participation. Registration is required.