Thraustochytrid hosts for expression of proteins relevant to SARS-CoV-2 intervention

Abstract

The emergence of COVID-19 as a global pandemic had sharply illustrated the limitations of research and development pipelines and scaled manufacturing. Although existing vaccines were created in record time, global deployment remains limited by regional production scales. Similarly, the most effective treatments for infected COVID-19 patients are also constrained by production scales as well as by the cost of production and thus expense per treatment. The need to produce these interventions more cost-effectively, at larger scales, in less time while retaining high quality is paramount. The ConamaxTM platform is based on a Thraustochytrid–an order of microorganisms well established in industry for world-scale production of omega-3 fatty acids by fermentation. Thraustochytrids, and the species Aurantiochytrium acetophilum in particular, possess a number of innate qualities which make it ideal for production of monoclonal antibodies and other biotherapeutic proteins. In this study, the Conamax system was used to produce several targets which may be relevant as interventions in the fight against COVID-19; an anti-SARS-CoV-2 antibody (CR3022), tocilizumab, and the ACE2 receptor. Our system was capable of producing all of these targets and each was assayed in vitro for an activity which confirmed proper structural folding. Purified CR3022 antibody produced from Conamax was capable of reducing the cytopathic effect of SARS-CoV-2. Conamax-derived tocilizumab was shown to bind to its target IL6R. Both the full-length and soluble versions of ACE2 protein produced in the Conamax platform exhibited ACE2-specific proteolytic activity. These data indicate that the Conamax platform has great potential in the production of therapeutic agents.

Marine thraustochytrid: exploration from taxonomic challenges to biotechnological applications

“…Besides, some natural products such as terpenoids in thraustochytrids could exert antioxidant effect, thus substitute for the antioxidants and pigments chemicals in cosmetics. In addition, thraustochytrids had exhibited anti-inflammatory and anti-cancer activities (Shakeri et al, 2017;Takahashi et al, 2019), and were proposed to be used to develop oral vaccines for their beneficial characters (Dahmen et al, 2023). The active lipids and defatted byproducts of thraustochytrids with important nutritional value, have great potential in the development of functional food (Paulo et al, 2020;Reboleira et al, 2021).…”

“…Studies evaluating the toxicological potential of unextracted A. limacinum biomass as a food additive observed no significant mutagenic activity, genotoxic activity, induction of genotoxicity in human lymphocytes and death or acute toxicity (Dillon et al, 2020). Additionally, scientists have already initiated attempts to produce anti-SARS-CoV-2 antibodies related to interventions for Coronavirus disease 2019 (COVID-19) using A. acetophilum as a host (Dahmen et al, 2023). Furthermore, the development of novel functional foods enriched with DHA, particularly a yogurt enriched with A. sp.…”