The RxLR Motif of the Host Targeting Effector AVR3a of Phytophthora infestans Is Cleaved Before Secretion

Our work is supported by the BBSRC (SW, CJS, PvW), NERC (PvW) and the University of Aberdeen (CJS, PvW, ID). This work was supported by EU East-NMR FP7 Project (Contract 228461) and Polish National Centre for Research and Development under research grant number 178479 (contract number PBS1/A9/ 13/2012) (for IZ). We would like to acknowledge Kevin MacKenzie of the core microscopy facility of the University of Aberdeen for helpful suggestions and Prof. Regine Kahmann for critical reading of the manuscript. On behalf of all authors, the ASPB journals deposit final published articles in PubMed Central for release 12 months after the date of publication (unless a free-access option applies). The final pdf of the article will be open access.Peer reviewedPublisher PD

Development of a cost-effective ovine antibody-based therapy against SARS-CoV-2 infection and contribution of antibodies specific to the spike subunit proteins.

Antibodies against SARS-CoV-2 are important to generate protective immunity, with convalescent plasma one of the first therapies approved. An alternative source of polyclonal antibodies suitable for upscaling would be more amendable to regulatory approval and widespread use. In this study, sheep were immunised with SARS-CoV-2 whole spike protein or one of the subunit proteins: S1 and S2. Once substantial antibody titres were generated, plasma was collected and samples pooled for each antigen. Non-specific antibodies were removed via affinity-purification to yield candidate products for testing in a hamster model of SARS-CoV-2 infection. Affinity-purified polyclonal antibodies to whole spike, S1 and S2 proteins were evaluated for in vitro for neutralising activity against SARS-CoV-2 Wuhan-like virus (Australia/VIC01/2020) and a recent variant of concern, B.1.1.529 BA.1 (Omicron), antibody-binding, complement fixation and phagocytosis assays were also performed. All antibody preparations demonstrated an effect against SARS-CoV-2 disease in the hamster model of challenge, with those raised against the S2 subunit providing the most promise. A rapid, cost-effective therapy for COVID-19 was developed which provides a source of highly active immunoglobulin specific to SARS-CoV-2 with multi-functional activity

Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments

Abstract The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab′)2 fragments. These preparations were evaluated for in vitro activity and demonstrated to be strongly neutralising against a range of SARS-CoV-2 strains, including Omicron B2.2. In addition, their protection against disease manifestations and viral loads were assessed using a hamster SARS-CoV-2 infection model. Results demonstrated protective effects of both IgG and F(ab′)2, with the latter requiring sequential dosing to maintain in vivo activity due to rapid clearance from the circulation