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#Medsky🧪 #IDsky #Immunodky #publichealth Understanding the bacterial response to #antibiotic Tx remains a major area of research. Recent findings have indicated that bacterial metabolism — the collective sum of all catabolic & anabolic processes involving diverse genes,
March 16, 2025 at 10:13 PM
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#Medsky🧪 #idsky #immunodky #pharmasky #publichealth Review discusses how #vaccine #adjuvants function & highlight knowledge gaps that need to be addressed to develop improved vaccines against emerging pathogens. @sciimmunology.bsky.social
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Adjuvant mechanisms of action at the injection site. Antigen depots control the rate of antigen release at the injection site, where local inflammation and slow release of both antigen and adjuvant components influence cytokine and chemokine release and subsequent immune cell infiltration from the circulation. Adjuvants can also improve antigen capture by DCs and lymphatic drainage by nanoscale-particulate antigens and increase lymphatic flow leading to enhancement of the immune response.CREDIT: A FISHER/SCIENCE IMMUNOLOGY Adjuvant effects in the draining lymph node. Adjuvants can have many effects at the draining lymph nodes, including (1) increasing lymph flow; (2) inducing deletion of sinus-lining macrophages, promoting antigen entry into the lymph node parenchyma; (3) promoting antigen capture on follicular DCs in GCs, e.g., via slow antigen release that promotes early immune complex formation or complement activation; (4) inducing the production of inflammatory cytokines and chemokines; (5) promoting influx of innate and adaptive immune cells from circulation; (6) activating innate immune cells, including APCs that up-regulate costimulatory receptors and prepare to present antigen to lymphocytes; and (7) promoting antigen processing and presentation, including cross-presentation of antigen to CD8 T cells by DCs.CREDIT: A FISHER/SCIENCE IMMUNOLOGY Chemical structures of molecular adjuvants. Adjuvants in use alone or in combination, including the TLR4 agonist monophosphoryl lipid A (MPLA), STING agonist cyclic guanosine 5′-monophosphate (GMP)–adenosine 5′-monophosphate (AMP) (c-GAMP), QS-21 saponin, and TLR7/8 agonist imidazoquinoline 3M-052.CREDIT: A FISHER/SCIENCE IMMUNOLOGY Adjuvant classes and structures. (A) Depot-forming adjuvants retain antigen for slow release and/or promote immune cell recruitment to the injection site to enable antigen capture and trafficking to draining lymph nodes. Examples of depot-forming adjuvants include aluminum salts, hydrogels, and cationic liposomes. (B) Oil-in-water or water-in-oil emulsions promote innate immune activation through inflammasome activation and induction of cell stress at the injection site and/or draining lymph nodes. (C) Saponins derived from Q. saponaria bark activate inflammasomes, trigger cytokine production, and increase lymph flow. (D) DAMPs or pathogen-associated molecular patterns (PAMPs) are ligands that activate specific pattern recognition receptors like TLRs or other sensors. (E) Combination adjuvant formulations. Transmission electron micrograph in (C) modified from
February 17, 2025 at 8:44 PM