The closely related mycobacteria responsible for tuberculosis produce an unusually high number of secreted proteins, many of which are clearly implicated in pathogenesis and protective immunity. Falling within this category are the closely related proteins MPB70 and MPB83. The structure of MPB70 reveals a complex and novel bacterial fold, which has clear structural homology to the two C-terminal FAS1 domains of the cell adhesion protein fasciclin I, whose structures were reported very recently. Assessment of the surface features of MPB70, the sequence divergence between MPB70 and MPB83, the conservation of residues across a group of FAS1 domains, and the locations of disease-inducing mutations in ␤ig-h3 strongly suggests that MPB70 and MPB83 contain two functional surfaces on opposite faces, which are probably involved in binding to host cell proteins. This analysis also suggests that these functional surfaces are retained in the FAS1 proteins associated with mediating interactions between cells and the extracellular matrix (fasciclin I, periostin, and ␤ig-h3) and furthermore that some of the human corneal disease-inducing substitutions identified in ␤ig-h3 will perturb interactions at these sites.Tuberculosis remains one of the most significant infectious diseases of humans, with about one-third of the world's population currently infected resulting in about 3 million deaths annually (1, 2). The bacteria responsible for tuberculosis belong to the Mycobacterium tuberculosis complex, which is a group of highly related mycobacteria. The complex includes M. tuberculosis, which causes the majority of human tuberculosis, and Mycobacterium bovis, which leads to tuberculosis in a range of domesticated and wild animals. Analysis of the complete M. tuberculosis H37Rv genome has identified the genes for 4006 proteins (3, 4), however, it has so far proved possible to assign specific functions to only about half of the predicted proteins. In addition, we still have relatively little information about which M. tuberculosis complex proteins are essential for pathogenesis, or associated with the stimulation of protective immunity, and even less knowledge of their structures, functions, and mechanisms of action. The finding that only live mycobacterial vaccines provide significant protection against tuberculosis infection (5) clearly indicates a key role for secreted M. tuberculosis complex proteins in stimulating protective immunity and highlights the importance of investigating major secreted antigenic proteins such as MPB70, MPB83, ESAT-6, and CFP-10 (6 -10).The mature M. bovis protein MPB70 and its identical M. tuberculosis homologue MPT70 (Rv2875) are stable, 163-residue polypeptides, that are efficiently secreted from mycobacterial cells following cleavage of a 30-residue signal peptide (3, 6). The proteins contain a single disulfide bond linking Cys-8 and Cys-142 but show no other form of post-translational modification. MPB70 is a major serodominant antigen of M. bovis, which also stimulates cellular immune responses du...

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Background Passive immune therapies may be useful in mitigating severe COVID-19. The hamster model has been successfully used to study efficacy of COVID-19 treatments. Our objective with this research is to demonstrate initial efficacy of a new polyclonal ovine Fab raised against the SARS-CoV-2 spike protein (PR020) as a treatment for COVID-19. Methods Hamsters were treated with PR020 via intraperitoneal route at a dose of 120 mg/kg or a vehicle control once every 24 hours for 8 days, starting 1 day prior to viral challenge with Victoria/1/2020 SARS-CoV-2. Sampling to detect viral RNA and clinical observations were taken throughout the challenge phase. Necropsy occurred 1 day following the last dose of PR020, and tissues were assessed for histopathology and viral RNA. Results Hamsters receiving vehicle alone lost weight more rapidly than the PR020 group (Figure 1, p< 0.05 day 4 onward). Clinical illness scores for the PR020 group were lower compared to control animals (Figure 2, p< 0.05 day 3 onward). While viral shedding assessed by throat swab did not differ between groups, viral RNA levels in lung tissue was significantly lower in PR020-treated animals (Figure 3, p< 0.05). PR020-treated animals also showed significantly less pathological changes in the lung compared to controls (Figure 4, p=0.0022). FIGURE 1.Weight of Hamsters Receiving PR020 Compared to Controls.FIGURE 2.Clinical Scores of Hamsters Receiving PR020 Compared to Controls.FIGURE 3.Viral RNA Levels in Lungs of Hamsters Receiving PR020 Compared to Control. Conclusion Treatment with PR020 resulted in a positive clinical outcome (e.g. less weight loss and lower clinical signs). While treatment appeared to have little effect in the nasopharynx, there was a positive effect in the lower respiratory tract, with substantially less viral RNA in the lungs of the group given PR020 and a decrease in the lung histopathology, including consolidation. FIGURE 4.Histopathology Results: Lung Consolidation Scores and Total Histopathology Scores for Lung and Nasal Cavity. Disclosures Zainab Bascal, PhD, BTG International Inc: Employee Aled Griffiths, BSc, BTG International Inc: Employee of BTG Ellen Dentten, PhD, BTG International Inc: Employee of BTG Christon Hill, BSc, MBA, BTG International Inc: Employee of BTG Suzanne Ward, PharmD, BTG International Inc: Employee of BTG.