RESUMO
SARS-CoV-2-neutralizing antibodies are promising therapeutics for COVID-19. However, little is known about the mechanisms of action of these antibodies or their effective dosing windows. We report the discovery and development of SC31, a potent SARS-CoV-2 neutralizing IgG1 antibody, originally isolated from a convalescent patient at day 27 after the onset of symptoms. Neutralization occurs via a binding epitope that maps within the ACE2 interface of the SARS-CoV-2 Spike protein, conserved across all common circulating SARS-CoV-2 mutants. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, SC31 demonstrated potent survival benefit by dramatically reducing viral load concomitant with attenuated pro-inflammatory responses linked to severe systemic disease, such as IL-6. Comparison with a Fc-null LALA variant of SC31 demonstrated that optimal therapeutic efficacy of SC31 requires intact Fc-mediated effector functions that can further induce an IFN{gamma}-driven anti-viral immune response. Dose-dependent efficacy for SC31 was observed down to 5mg/kg when dosed before the activation of lung inflammatory responses. Importantly, despite Fc{gamma}R binding, no evidence of antibody dependent enhancement was observed with the Fc-competent SC31 even at sub-therapeutic doses. Therapeutic efficacy was confirmed in SARS-CoV-2-infected hamsters, where SC31 again significantly reduced viral load, decreased lung lesions and inhibited progression to severe disease manifestations. This study underlines the potential for significant COVID-19 patient benefit for the SC31 antibody that justifies rapid advancement to the clinic, as well as highlighting the importance of appropriate mechanistic and functional studies during development. One Sentence SummaryAnti-SARS-CoV-2 IgG1 antibody SC31 controls infection in vivo by blocking SP:ACE2 binding and triggering a Fc-mediated anti-viral response.
RESUMO
AIM: To investigate the changes of corneal cytology of patients with different degrees of xerophthalmia of the types of deficient aqueous production and over evaporation with confocal microscopy. METHODS:Retrospective case series was adopted with three - dimensional corneal topography and anterior segment analysis system (Sirius system). A total of 33 typical dry eye patients (total 65 eyes) with deficient aqueous production and 28 typical dry eye patients (total 55 eyes) with over evaporation were selected from optical center of the First Affiliated Hospital of Harbin Medical University from December 2016 to June 2017, which were grading according to dry eye degrees. The corneal epithelial cell (surface epithelial cell, pterygoid epithelial cell, basal epithelial cell), Langerhans cell (dendritic cell),stroma (deep stromal layer and superficial stromal layer), the density and form of endothelial cells were observed and analyzed with the confocal microscope. RESULTS: Confocal microscope showed that the number of corneal epithelial cells decreased with the increasing of dry eye severity in patients with tear deficiency and evaporative. The results were statistically significant (P<0.01). The sizes of each layer of corneal epithelium cells were uneven, and the arrangement was irregular. The diameter of corneal sub-epithelial nerve fiber of deficient aqueous production dry eye became thinner with irregular arrangement. With the increase in severity of dry eye,the degree of curvature and branches gradually increased. The activation degree of Langerhans cells of evaporative dry eye was directly proportional to the severity of dry eye(P<0 01). There was no significant changes in the number of superficial stromal cells in the two types of dry eye (P>0 05). The number of deep stromal cells in the two types of dry eye had no relations with the severity of dry eye (P>0. 05). There was no significant changes in the number of corneal endothelial cells in the two types of dry eye (P>0.05). CONCLUSION:The Sirius system can be used for non-contact and non-invasive examination and classification. And there is changes of the density and morphology in each layers of cornea cells of two types of dry eye with the confocal microscope.
