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Abstract Parasitic helminths secrete extracellular vesicles (EVs) into their host tissues to modulate immune responses, but the underlying mechanisms are poorly understood. We demonstrate that Ascaris EVs are efficiently internalised by monocytes in human peripheral blood mononuclear cells and increase the percentage of classical monocytes. Furthermore, EV treatment of monocytes induced a novel anti‐inflammatory phenotype characterised by CD14+, CD16−, CC chemokine receptor 2 (CCR2−) and programmed death‐ligand 1 (PD‐L1)+ cells. In addition, Ascaris EVs induced T cell anergy in a monocyte‐dependent mechanism. Targeting professional phagocytes to induce both direct and indirect pathways of immune modulation presents a highly novel and efficient mechanism of EV‐mediated host‐parasite communication. Intra‐peritoneal administration of EVs induced protection against gut inflammation in the dextran sodium sulphate model of colitis in mice. Ascaris EVs were shown to affect circulating immune cells and protect against gut inflammation; this highlights their potential as a subject for further investigation in inflammatory conditions driven by dysregulated immune responses. However, their clinical translation would require further studies and careful consideration of ethical implications.

Abstract Spirulina is an edible cyanobacterium that increasingly gaining recognition for it untapped potential in the biomanufacturing of pharmaceuticals. Despite the rapidly accumulating information on extracellular vesicles (EVs) from most other bacteria, nothing is known about Spirulina extracellular vesicles (SPEVs). This study reports the successful isolation, characterization and visualization of SPEVs for the first time and it further investigates the potential therapeutic benefits of SPEVs using a mouse model. SPEVs were isolated using ultracentrifugation and size‐exclusion‐chromatography. Cryo‐Transmission Electron Microscopy revealed pleomorphic outer‐membrane‐vesicles and outer‐inner‐membrane‐vesicles displaying diverse shapes, sizes and corona densities. To assess short‐ and long‐term immune responses, mice were injected intraperitoneally with SPEVs, which demonstrated a significant increase in neutrophils and M1 macrophages at the injection site, indicating a pro‐inflammatory effect induced by SPEVs without clinical signs of toxicity or hypersensitivity. Furthermore, SPEVs demonstrated potent adjuvanticity by enhancing antigen‐specific IgG responses in mice by over 100‐fold compared to an unadjuvanted model vaccine antigen. Mass‐spectrometry identified 54 proteins within SPEVs, including three protein superfamily members linked to the observed pro‐inflammatory effects. Our findings highlight the potential of SPEVs as a new class of vaccine adjuvant and warrant additional studies to further characterize the nature of the immune response.