Antibody-dependent Enhancement Research Articles

Injectable Micro-Hydrogel for DNA Delivery: A Promising Therapeutic Platform.

Utilizing the immune system as a strategy for disease prevention and treatment is promising, especially with dendritic cells (DCs) playing a central role in adaptive immune responses. The unique properties of DCs drive interest in developing materials for cell-based therapy and immune modulation. Injectable systems require syringe-compatible scaffolds, while hydrogels, like alginate, known for their programmability and biocompatibility, offer a versatile platform for immune medicine enhancement through easy preparation and room-temperature cross-linking. In this study, we synthesized alginate balls loaded with DCs or cytosine-phosphorothioate-guanine deoxyribonucleotide (CpG DNA) microparticles, aiming for long-term immune cell culture with potential immune stimulation effects. Encapsulated DCs exhibited proliferation within the alginate balls for up to 7 days, and CpG MPs were uniformly dispersed, which can facilitate uptake by DCs. This was supported by the result that DCs effectively phagocytosed CpG microparticles in a 2D environment. After the uptake of CpG MPs, the alginate balls with CpG-MP-uptaken DCs were synthesized successfully. The injectable properties of the alginate balls were easily modulated by adjusting the syringe needle gauges. This innovative strategy holds substantial promise for advancing medical treatments, offering effective and comfortable solutions for controlled immune modulation.

Evaluation of Immune Function Enhancement and Clinical Symptom Alleviation in Epilepsy Patients Post-Topiramate Administration

Evaluation of Immune Function Enhancement and Clinical Symptom Alleviation in Epilepsy Patients Post-Topiramate Administration

Abstract 1595 Immune enhancement effects of neutral lipids, glycolipids, phospholipiids from Halocynthia aurantium tunic on RAW264.7 macrophages

Abstract 1595 Immune enhancement effects of neutral lipids, glycolipids, phospholipiids from Halocynthia aurantium tunic on RAW264.7 macrophages

Therapeutic potential of popular fermented dairy products and its benefits on human health.

In the current arena of time, the transformation of society has improved the standard of living in terms of lifestyle and their nutritional demands and requirements. The microorganisms under controlled conditions and the enzymatic transformation of dietary components are the processes that resulted in fermented foods and beverages. Fermented dairy products with high nutritional value are "the pearls of the dairy industry." During fermentation, fermented dairy products produce bioactive compounds and metabolites derived from bacteria. Research indicates the beneficial effects of probiotics found in dairy products on human health is making lightning-fast headway these days. The utilization of lactic acid bacteria as probiotics for the prevention or treatment of disease has been a driving force behind the discovery of novel potential probiotics found in naturally fermented milk. Probiotics such as lactic acid bacteria and bifidobacteria found in fermented dairy products have a variety of health benefits, including innate immune enhancement, diarrhea treatment, inflammatory bowel disease, diabetes, Tuberculosis, and obesity, relieving irritable bowel disease symptoms, preventing cancer, improving lactose tolerance, lowering cholesterol, enhancing antioxidant activity, and antimicrobial activity against pathogens. This review aims to evaluate the therapeutic efficacy and nutritional and microbiological properties of popular fermented dairy products and their health benefits.

A novel lentiviral vector-based approach to generate chimeric antigen receptor T cells targeting Aspergillus fumigatus.

Invasive aspergillosis (IA) is a common and deadly mold infection in immunocompromised patients. As morbidity and mortality of IA are primarily driven by poor immune defense, adjunct immunotherapies, such as chimeric antigen receptor (CAR) T cells, are direly needed. Here, we propose a novel approach to generate Aspergillus fumigatus (AF)-CAR T cells using the single-chain variable fragment domain of monoclonal antibody AF-269-5 and a lentiviral vector system. These cells successfully targeted mature hyphal filaments of representative clinical and reference AF isolates and elicited a potent release of cytotoxic effectors and type 1 T cell cytokines. Furthermore, AF-CAR T cells generated from peripheral blood mononuclear cells of four healthy human donors and expanded with either of three cytokine stimulation regimens (IL-2, IL-2 + IL-21, or IL-7 + IL-15) significantly suppressed mycelial growth of AF-293 after 18 hours of co-culture and synergized with the immunomodulatory antifungal agent caspofungin to control hyphal growth for 36 hours. Moreover, cyclophosphamide-immunosuppressed NSG mice with invasive pulmonary aspergillosis that received two doses of 5 million AF-CAR T cells (6 and 48 hours after AF infection) showed significantly reduced morbidity on day 4 post-infection (P < 0.001) and significantly improved 7-day survival (P = 0.049) compared with mice receiving non-targeting control T cells, even without concomitant antifungal chemotherapy. In conclusion, we developed a novel lentiviral strategy to obtain AF-CAR T cells with high targeting efficacy, yielding significant anti-AF activity in vitro and short-term protection in vivo. Our approach could serve as an important steppingstone for future clinical translation of antifungal CAR T-cell therapy after further refinement and thorough preclinical evaluation.IMPORTANCEInvasive aspergillosis (IA) remains a formidable cause of morbidity and mortality in patients with hematologic malignancies and those undergoing hematopoietic stem cell transplantation. Despite the introduction of several new Aspergillus-active antifungals over the last 30 years, the persisting high mortality of IA in the setting of continuous and profound immunosuppression is a painful reminder of the major unmet need of effective antifungal immune enhancement therapies. The success of chimeric antigen receptor (CAR) T-cell therapy in cancer medicine has inspired researchers to translate this approach to opportunistic infections, including IA. Aiming to refine anti-Aspergillus CAR T-cell therapy and improve its feasibility for future clinical translation, we herein developed and validated a novel antibody-based CAR construct and lentiviral transduction method to accelerate the production of CAR T cells with high targeting efficacy against Aspergillus fumigatus. Our unique approach could provide a promising platform for future clinical translation of CAR T-cell-based antifungal immunotherapy.

Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection

The yellow fever 17D vaccine (YF17D) is highly effective but is frequently administered to individuals with pre-existing cross-reactive immunity, potentially impacting their immune responses. Here, we investigate the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus (TBEV) vaccine on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv) and 22 individuals sampled one-year pv. Our findings indicate that previous TBEV vaccination does not affect the early IgM-driven neutralizing response to YF17D. However, pre-vaccination sera enhance YF17D virus infection in vitro via antibody-dependent enhancement (ADE). Following YF17D vaccination, TBEV-pre-vaccinated individuals develop high amounts of cross-reactive IgG antibodies with poor neutralizing capacity. In contrast, TBEV-unvaccinated individuals elicit a non-cross-reacting neutralizing response. Using YF17D envelope protein mutants displaying different epitopes, we identify quaternary dimeric epitopes as the primary target of neutralizing antibodies. Additionally, TBEV-pre-vaccination skews the IgG response towards the pan-flavivirus fusion loop epitope (FLE), capable of mediating ADE of dengue and Zika virus infections in vitro. Together, we propose that YF17D vaccination conceals the FLE in individuals without prior flavivirus exposure but favors a cross-reactive IgG response in TBEV-pre-vaccinated recipients directed to the FLE with potential to enhance dengue virus infection.

Immuno-Enhancing Effects of Galium aparine L. in Cyclophosphamide-Induced Immunosuppressed Animal Models.

This study investigates the immunomodulatory potential of Galium aparine L. (GAE) in immunodeficient animals. In this study, animals were categorized into five groups: the normal group, CYP group (cyclophosphamide intraperitoneal injection), GA5 group (cyclophosphamide + 5 μg GAE), GA50 group (cyclophosphamide + 50 μg GAE), and GA500 group (cyclophosphamide + 500 μg GAE). The CYP group exhibited significantly reduced spleen weights compared to the normal group, while the groups obtaining GAE displayed a dose-dependent increase in spleen weight. Furthermore, the GAE demonstrated dose-dependent enhancement of splenocyte proliferating activity, with significant increases observed in both LPS and ConA-induced assays. NK cell activity significantly increased in the GA50 and GA500 groups compared to the CYP group. Cytokine analysis revealed a significant increase in IL-6, TNF-α, and IFN-γ levels in ConA-induced splenocytes treated with GAE. Gene expression analysis identified 2434 DEG genes in the extract groups. Notable genes, such as Entpd1, Pgf, Thdb, Syt7, Sqor, and Rsc1al, displayed substantial differences in individual gene expression levels, suggesting their potential as target genes for immune enhancement. In conclusion, Galium aparine L. extract exhibits immunomodulatory properties. The observed gene expression changes further support the potential of Galium aparine L. extract as a natural agent for immune augmentation.

Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression.

The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and the resulting immunosuppressive microenvironment, leading to the chronicity and recurrence of IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO2@Ce6@Van (BMCV). The BMCV exhibits precise targeting and adhesion to the S.aureus biofilm-infected region, coupled with its capacity to catalyze oxygen generation from H2O2 in the hypoxic and acidic biofilm microenvironment (BME), promoting oxygen-dependent photodynamic therapy efficacy while ensuring continuous release of manganese ions. Notably, targeted BMCV can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting the biofilm structure and impairing its barrier function, making it vulnerable to infiltration and elimination by the immune system. Furthermore, light-induced reactive oxygen species (ROS) around the biofilm can lyse S.aureus, triggering bacterium-like immunogenic cell death (ICD), releasing abundant immune costimulatory factors, facilitating the recognition and maturation of antigen-presenting cells (APCs), and activating adaptive immunity. Additionally, manganese ions in the BME act as immunoadjuvants, further amplifying macrophage-mediated innate and adaptive immune responses and reversing the immunologically cold BME to an immunologically hot BME. We prove that our synthesized BMCV elicits a robust adaptive immune response in vivo, effectively clearing primary IAIs and inducing long-term immune memory to prevent recurrence. Our study introduces a potent light-induced immunomodulatory nanoplatform capable of reversing the biofilm-induced immunosuppressive microenvironment and disrupting biofilm-mediated protective barriers, offering a promising immunotherapeutic strategy for addressing challenging S.aureus IAIs.

18β-glycyrrhetinic acid suppresses Lewis lung cancer growth through protecting immune cells from ferroptosis.

18β-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizic acid extracted from the root of licorice, has been reported to possess anti-cancer and immunomodulatory activity, but the mechanisms are not well understood. Recent studies have shown that ferroptosis of immune cells is involved in tumor-associated immune suppression. The purpose of this study was to investigate whether the enhanced immune response via inhibiting immune cell ferroptosis contributed to the anticancer effect of 18β-GA. Lewis Lung carcinoma mouse model and Murine CD8+T cell culture model were used to examine the changes of immune response and ferroptosis of immune cells. We found that 18β-GA was effective against lung cancer accompanied by enhanced activation of tumor-infiltrating CD8+ T cells in Lewis Lung carcinoma mouse model. Furthermore, we demonstrated that the boosted immune response by GA was attributed to its ability to inhibit arachidonic acid (AA)-mediated CD8+ T ferroptosis via suppressing CD36 expression. The findings of the present study unraveled a novel mechanism underlying the anti-cancer and immunomodulatory activity of 18β-GA and support that 18β-GA holds potential to be used as an immune enhancer for lung cancer prevention or treatment.

SESBANIA GRANDIFLORA LEAF EXTRACT ENHANCES GROWTH AND NON-SPECIFIC IMMUNE RESPONSES OF SHRIMP (Penaeus monodon)

This study determined the effects of Sesbania grandiflora (SG) leaf extract on the growth, feed utilization efficiency and non-specific immunological responses in black tiger shrimp (Penaeus monodon). Three diets were prepared by mixing the methanol extract of SG onto a pellet feed (34% protein) at concentrations of 0% (control), 0.05% (T1) and 0.1% (T2), respectively. Ten shrimps (mean weight 2.1g), were reared in each tank of 80 L, and the weight and immunological reaction of shrimp were received after a feeding trail of 28 days. The dietary extract treated shrimp had better growth performance (WG, SGR), and feed utilization efficiency (FCR, PER) compared to the control group. The treated shrimp exhibited enhanced immunological responses; the total haemocyte count, prophenoloxidase activity, superoxide dismutase activity, and shorter haemolymph clotting time compared to the control shrimp. In conclusion, a lower level of SG (0.05%) was found to be most effective in terms of immune response enhancement; hence, this plant could be a good source for feed additives for enhancing sustainable shrimp production.

A Comparative Study on Effects of Three Butyric Acid-Producing Additives on the Growth Performance, Non-specific Immunity, and Intestinal Microbiota of the Sea Cucumber Apostichopus japonicus.

The providers of butyric acid, Clostridium butyricum (CB), sodium butyrate (SB), and tributyrin (TB), have been extensively studied as aquafeed additives in recent years. However, no comparative study has been reported on the probiotic effects of CB, SB, and TB as feed additives on sea cucumber (Apostichopus japonicus). A 63-day feeding trial was performed to assess the effects of dietary live cells of C. butyricum (CB group, the basal diet supplemented with 1% CB), sodium butyrate (SB group, the basal diet supplemented with 1% SB), and tributyrin (TB group, the basal diet supplemented with 1% TB) on the growth, non-specific immunity, and intestinal microbiota of A. japonicus with a basal diet group as the control. Results indicated that all three additives considerably increased A. japonicus growth, with dietary CB having the optimal growth-promoting effect. Of the seven non-specific enzyme parameters measured in coelomocytes of A. japonicus (i.e., the activities of phagocytosis, respiratory burst, superoxide dismutase, alkaline phosphatase, acid phosphatase, catalase, and lysozyme), dietary CB, SB, and TB considerably increased the activities of six, five, and six of them, respectively. The immune genes (Aj-p105, Aj-p50, Aj-rel, and Aj-lys) expression in the mid-intestine tissues of A. japonicus was significantly increased by all three additives. The CB group had the highest expression of all four genes. Additionally, the relative expression of Aj-p105, Aj-p50, and Aj-lys genes was significantly up-regulated in the three additive groups after stimulation with inactivated Vibrio splendidus. Dietary CB enhanced the intestinal microbial diversity and richness in A. japonicus while dietary TB decreased them. Meanwhile, dietary CB, SB, and TB significantly enhanced the abundance of Firmicutes, unclassified_f_Rhodobacteraceae, and Proteobacteria, respectively, while dietary CB and SB reduced the abundance of Vibrio. Dietary CB and SB improved the stability of microbial ecosystem in the intestine of A. japonicus. In contrast, dietary TB appeared to have a negative effect on the stability of intestinal microbial ecosystem. All three additives improved the intestinal microbial functions associated with energy production and immunity regulation pathways, which may contribute directly to growth promotion and non-specific immunity enhancement in A. japonicus. Collectively, in terms of enhancing growth and non-specific immunity, as well as improving intestinal microbiota, dietary live cells of C. butyricum exhibited the most effective effects in A. japonicus.

Effects of glycyrrhiza polysaccharides on growth performance, meat quality, serum parameters and growth/meat quality-related gene expression in broilers.

With growing restrictions on the use of antibiotics in animal feed, plant extracts are increasingly favored as natural feed additive sources. Glycyrrhiza polysaccharide (GP), known for its multifaceted biological benefits including growth promotion, immune enhancement, and antioxidative properties, has been the focus of recent studies. Yet, the effects and mechanisms of GP on broiler growth and meat quality remain to be fully elucidated. This study aimed to investigate the effects of GP on growth, serum biochemistry, meat quality, and gene expression in broilers. The broilers were divided into five groups, each consisting of five replicates with six birds. These groups were supplemented with 0, 500, 1,000, 1,500, and 2,000 mg/kg of GP in their basal diets, respectively, for a period of 42 days. The results indicated that from day 22 to day 42, and throughout the entire experimental period from day 1 to day 42, the groups receiving 1,000 and 1,500 mg/kg of GP showed a significant reduction in the feed-to-gain ratio (F:G) compared to the control group. On day 42, an increase in serum growth hormone (GH) levels was shown in groups supplemented with 1,000 mg/kg GP or higher, along with a significant linear increase in insulin-like growth factor-1 (IGF-1) concentration. Additionally, significant upregulation of GH and IGF-1 mRNA expression levels was noted in the 1,000 and 1,500 mg/kg GP groups. Furthermore, GP significantly elevated serum concentrations of alkaline phosphatase (AKP) and globulin (GLB) while reducing blood urea nitrogen (BUN) levels. In terms of meat quality, the 1,500 and 2,000 mg/kg GP groups significantly increased fiber density in pectoral muscles and reduced thiobarbituric acid (TBA) content. GP also significantly decreased cooking loss rate in both pectoral and leg muscles and the drip loss rate in leg muscles. It increased levels of linoleic acid and oleic acid, while decreasing concentrations of stearic acid, myristic acid, and docosahexaenoic acid. Finally, the study demonstrated that the 1,500 mg/kg GP group significantly enhanced the expression of myogenin (MyoG) and myogenic differentiation (MyoD) mRNA in leg muscles. Overall, the study determined that the optimal dosage of GP in broiler feed is 1,500 mg/kg.

Biomimetic engineered nanoparticles target drug-resistant tumor cells and heterogeneous blood vessels for combination therapy of osteosarcoma

Given that the treatment of drug-resistant osteosarcoma is a significant clinical challenge, in drug-resistant tumors, the role of endothelial cells has been recently emphasized. We noted that heterogeneous vascular endothelial cells (ONHVECs) in drug-resistant osteosarcoma tissues may inhibit macrophage-mediated killing of tumor cells, thus promoting the occurrence of drug resistance. Accordingly, we designed a type of hybrid membrane-coated multifunctional nanoparticle (NP), SiO2@PDA/Fe3+@Cis@HM. The NPs had good biocompatibility and enhanced the occurrence of low-temperature photothermal Fenton-like reactions. The hybrid membrane endowed the NPs with a tumor homing ability and homologous cell targeting ability, thus simultaneously targeting drug-resistant tumor cells and ONHVECs, in addition to killing tumor cells via efficient delivery of cisplatin and ROS produced by accelerated Fenton-like reactions. Through in vivo and in vitro experiments, we confirmed that SiO2@PDA/Fe3+@Cis@HM NPs efficiently killed tumor cells as well as ONHVECs. The endogenous exosomes produced by damaged ONHVECs induced anti-tumor M1 macrophage polarization to indirectly kill tumor cells and achieve synergistic therapy. This immune regulation was completely inherent and exhibited consistent efficacy, without ethical connotations. In conclusion, this multifunctional treatment strategy is the first to adopt a tumor cell/vascular endothelial cell double-targeted concept, which realized the direct killing of drug-resistant tumor cells and a natural immune enhancement response and could become a new paradigm for the treatment of drug-resistant osteosarcoma.

Polysaccharide from Atractylodes macrocephala Koidz Binding with Zinc Oxide Nanoparticles as a Novel Mucosal Immune Adjuvant for H9N2 Inactivated Vaccine.

H9N2 avian influenza poses a significant public health risk, necessitating effective vaccines for mass immunization. Oral inactivated vaccines offer advantages like the ease of administration, but their efficacy often requires enhancement through mucosal adjuvants. In a previous study, we established a novel complex of polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) and preliminarily demonstrated its immune-enhancing function. This work aimed to evaluate the efficacy of AMP-ZnONPs as adjuvants in an oral H9N2-inactivated vaccine and the vaccine's impact on intestinal mucosal immunity. In this study, mice were orally vaccinated on days 0 and 14 after adapting to the environment. AMP-ZnONPs significantly improved HI titers, the levels of specific IgG, IgG1 and IgG2a in serum and sIgA in intestinal lavage fluid; increased the number of B-1 and B-2 cells and dendritic cell populations; and enhanced the mRNA expression of intestinal homing factors and immune-related cytokines. Interestingly, AMP-ZnONPs were more likely to affect B-1 cells than B-2 cells. AMP-ZnONPs showed mucosal immune enhancement that was comparable to positive control (cholera toxin, CT), but not to the side effect of weight loss caused by CT. Compared to the whole-inactivated H9N2 virus (WIV) group, the WIV + AMP-ZnONP and WIV + CT groups exhibited opposite shifts in gut microbial abundance. AMP-ZnONPs serve as an effective and safe mucosal adjuvant for oral WIV, improving cellular, humoral and mucosal immunity and microbiota in the gastrointestinal tract, avoiding the related undesired effects of CT.

Transcriptomic Analysis Reveals the Potential Mechanisms for Improving Carotenoid Production in Rhodosporidium toruloides Z11 under Light Stress.

Carotenoids, as a type of tetraterpene compound, have been widely used in food, medical, and health areas owing to their antioxidant, immune enhancement, and disease risk reduction effects. Rhodosporidium toruloides is a promising oleaginous red yeast that can industrially synthesize carotenoids. In this study, the effects of different light exposure times and intervals on carotenoid production by R. toruloides Z11 were first investigated. Results showed that a higher carotenoid content (1.29 mg/g) can be achieved when R. toruloides Z11 was exposed to light for 12 h per day, which was increased by 1.98 times compared with that of dark cultivation. Transcriptome profiling revealed that light stress could effectively promote the gene expression levels of GGPS1 and AL1 in the carotenoid biosynthesis pathway and phr in the DNA photolysis pathway of R. toruloides. This work will provide a molecular foundation to further improve the production efficiency of carotenoids by genetic engineering.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

Construction of recombinant Lactococcus expressing thymosin and interferon fusion protein and its application as an immune adjuvant

BackgroundIn recent years, biosafety and green food safety standards have increased the demand for immune enhancers and adjuvants. In the present study, recombinant food-grade Lactococcus lactis (r-L. lactis-Tα1-IFN) expressing thymosin Tα1 and chicken interferon fusion protein was constructed.ResultsThe in vitro interactions with macrophages revealed a mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate both macrophage J774-Dual™ NF-κB and interferon regulator (IRF) signaling pathways. In vitro interactions with chicken peripheral blood mononuclear cells (PBMCs) demonstrated that a mixture of recombinant r-L. lactis-Tα1-IFN significantly enhanced the expression levels of interferon (IFN)-γ, interleukin (IL)-10, CD80, and CD86 proteins in chicken PBMCs. Animal experiments displayed that injecting a lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly activate the proliferation of T cells and antigen-presenting cells in chicken PBMCs. Moreover, 16S analysis of intestinal microbiota demonstrated that injection of the lysis mixture of recombinant r-L. lactis-Tα1-IFN could significantly improve the structure and composition of chicken intestinal microbiota, with a significant increase in probiotic genera, such as Lactobacillus spp. Results of animal experiments using the lysis mixture of recombinant r-L. lactis-Tα1-IFN as an immune adjuvant for inactivated chicken Newcastle disease vaccine showed that the serum antibody titers of the experimental group were significantly higher than those of the vaccine control group, and the expression levels of cytokines IFN-γ and IL-2 were significantly higher than those of the vaccine control group.ConclusionThese results indicate that food-safe recombinant r-L. lactis-Tα1-IFN has potential as a vaccine immune booster and immune adjuvant. This study lays the foundation for the development of natural green novel animal immune booster or immune adjuvant.

Myeloid Cell-Triggered In Situ Cell Engineering for Robust Vaccine-Based Cancer Treatment.

Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g., tumor types, safety issues such as cytokine storms, and therapeutic benefits). Here, it is shown that an in situ injected macroporous myeloid cell adoptive scaffold (MAS) not only actively delivers antigens (Ags) that are triggered by scaffold-infiltrating cell surface thiol groups but also releases granulocyte-macrophage colony-stimulating factor and other adjuvant combos. Consequently, this promotes cell differentiation, activation, and migration from the produced monocyte and DC vaccines (MASVax) to stimulate antitumor T-cell immunity. Neoantigen-based MASVax combined with immune checkpoint blockade induces rejection of established tumors and long-term immune protection. The combined depletion of immunosuppressive myeloid cells further enhances the efficacy of MASVax, indicating the potential of myeloid cell-based therapies for immune enhancement and normalization treatment of cancer.

Metabolomic landscape of macrophage discloses an anabolic signature of dengue virus infection and antibody-dependent enhancement of viral infection.

Dengue virus (DENV) infection causes dengue fever, the most prevalent arthropod-transmitted viral disease worldwide. Viruses are acellular parasites and obligately rely on host cell machinery for reproduction. Previous studies have indicated metabolomic changes in endothelial cell models and sera of animal models and patients with dengue fever. To probe the immunometabolic mechanism of DENV infection, here, we report the metabolomic landscape of a human macrophage cell model of DENV infection and its antibody-dependent enhancement. DENV infection of THP-1-derived macrophages caused 202 metabolic variants, of which amino acids occupied 23.7%, fatty acids 21.78%, carbohydrates 10.4%, organic acids 13.37%, and carnitines 10.4%. These metabolomic changes indicated an overall anabolic signature, which was characterized by the global exhaustion of amino acids, increases of cellular fatty acids, carbohydrates and pentoses, but decreases of acylcarnitine. Significant activation of metabolic pathways of glycolysis, pentose phosphate, amino acid metabolism, and tricarboxylic acid cycle collectively support the overall anabolism to meet metabolic demands of DENV replication and immune activation by viral infection. Totally 88 of 202 metabolic variants were significantly changed by DENV infection, 36 of which met the statistical standard (P<0.05, VIP>1.5) of differentially expressed metabolites, which were the predominantly decreased variants of acylcarnitine and the increased variants of fatty acids and carbohydrates. Remarkably, 11 differentially expressed metabolites were significantly distinct between DENV only infection and antibody-dependent enhancement of viral infection. Our data suggested that the anabolic activation by DENV infection integrates the viral replication and anti-viral immune activation.

An In Vitro Assay to Examine the Antibody-Dependent Enhancement of Viral Infection

An In Vitro Assay to Examine the Antibody-Dependent Enhancement of Viral Infection