Protein-coated microcrystals (PCMCs) were investigated as potential vaccine formulations for a range of model antigens. Presentation of antigens as PCMCs increased the antigen-specific IgG responses for all antigens tested, compared to soluble antigens. When compared to conventional aluminium-adjuvanted formulations, PCMCs modified with calcium phosphate (CaP) showed enhanced antigen-specific IgG responses and a decreased antigen-specific IgG1:IgG2a ratio, indicating the induction of a more balanced Th1/Th2 response. The rate of antigen release from CaP PCMCs, in vitro, decreased strongly with increasing CaP loading but their immunogenicity in vivo was not significantly different, suggesting the adjuvanticity was not due to a depot effect. Notably, it was found that CaP modification enhanced the phagocytosis of fluorescent antigen-PCMC particles by J774.2 murine monocyte/macrophage cells compared to soluble antigen or soluble PCMCs. Thus, CaP PCMCs may provide an alternative to conventional aluminium-based acellular vaccines to provide a more balanced Th1/Th2 immune response.
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http://dx.doi.org/10.1016/j.vaccine.2013.09.061 | DOI Listing |
BMC Infect Dis
January 2025
Department of Tuberculosis Diseases, The Sixth People's Hospital of Dongguan, Dongguan, GuangDong, China.
Background: Exosome is a small extracellular vesicle with a diameter of 30 to 150 nm that is secreted by cells. Mtb and other bacteria can also secrete extracellular vesicles, which carry characteristics and information about the pathogen. Here, we compare the concentration of exosomes and the Mtb antigen in exosomes of tuberculosis patients aiming to evaluate whether exosomes can be used as diagnostic markers of tuberculosis at different stages.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biological Sciences, Virginia Tech, Blacksburg, VA, 24061-0910, USA.
Sepsis is a leading cause of death worldwide, with most patient mortality stemming from lingering immunosuppression in sepsis survivors. This is due in part to immune dysfunction resulting from monocyte exhaustion, a phenotype of reduced antigen presentation, altered CD14/CD16 inflammatory subtypes, and disrupted cytokine production. Whereas previous research demonstrated improved sepsis survival in Ticam2 mice, the contribution of TICAM2 to long-term exhaustion memory remained unknown.
View Article and Find Full Text PDFNature
January 2025
Immuno-Oncology Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.
View Article and Find Full Text PDFNature
January 2025
Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China.
Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers. T cells participate in a wide range of inflammatory diseases such as psoriasis, Crohn's disease, oesophagitis and multiple sclerosis, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities.
View Article and Find Full Text PDFNat Commun
January 2025
Carisma Therapeutics Inc, Philadelphia, PA, USA.
We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.
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