Developing immune-regulatory materials using immobilized monosaccharides with immune-instructive properties

New strategies for immune modulation have shown real promise in regenerative medicine as well as the fight against autoimmune diseases, allergies and cancer. Dendritic cells (DCs) are gatekeepers of the immune system and their ability in shaping the adaptive immune responses makes DCs ideal targets for immune modulation. Carbohydrates are abundant in different biological systems and are known to modulate DC phenotype and function. However, how simple monosaccharides instruct DC function is less well understood. In this study we used a combinatorial array of immobilized monosaccharides to investigate how they modulate DC phenotype and function, and crucially the impact of such changes on downstream adaptive immune responses. Our data show a selection of monosaccharides significantly suppress lipopolysaccharide (LPS) induced DC activation as evidenced by reduction in CD40 expression, IL-12 production and 2,3 indoleamine dioxygenase activity, while inducing a significant increase in IL-10 production. These changes are indicative of induction of an anti-inflammatory or regulatory phenotype in DCs which was further confirmed in DC-T cell co-cultures where DCs cultured on the ‘regulatory’ monosaccharaide coated surfaces were shown to induce naïve T cell polarization towards regulatory phenotype. Our data also highlighted a selection of monosaccharides that are able to promote mixed Treg and Th17 cell differentiation, a T cell phenotype expected to be highly immune suppressive. These data show the potential immunomodulatory effects of immobilized monosaccharides in priming DCs and skewing T cell differentiation towards an immune-regulatory phenotype. The ability to fine tune immune responses using these simple carbohydrate combinations (e.g. as coatings for existing materials) can be utilized as novel tools for immune modulation with potential applications in regenerative medicine, implantable medical devices and wound healing where reduction of inflammatory responses and maintaining immune homeostasis are desirable

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population