Clinical Characteristics and Patterns of Immune Responses in COVID-19 Patients From a Rural Community Hospital.

Background Although demographic and clinical factors such as age, certain comorbidities, and sex have been associated with COVID-19 outcomes, these studies were largely conducted in urban populations affiliated with large academic medical centers. There have been very few studies focusing on rural populations that also characterize broader changes in inflammatory cytokines and chemokines. Methodology A single-center study was conducted between June 2020 and March 2021 in Abilene, Texas, USA. Patients were included if they presented to the hospital for treatment of COVID-19, had extra biological materials from routine care available, and were between the ages of 0 to 110 years. There were no exclusion criteria. Patient characteristics, symptom presentation, and clinical laboratory results were extracted from electronic health records. Blood specimens were analyzed by protein microarray to quantitate 40 immunological biomarkers. Results A total of 122 patients were enrolled, of whom 81 (66%) were admitted to the general non-critical inpatient unit, 37 (30%) were admitted to the intensive or critical care units, and four (3.2%) were treated outpatient. Most hospitalized COVID-19 patients in this rural population were elderly, male, obese, and retired individuals. Predominant symptoms for non-critical patients were shortness of breath, fever, and fatigue. Ferritin levels for outpatient patients were lower on average than those in an inpatient setting and lactate dehydrogenase (LDH) levels were noted to be lower in non-critical and outpatient than those in the intensive care unit setting. Inflammatory biomarkers were positively correlated and consistent with inflammatory cascade. Interleukin (IL)-10 was positively correlated while platelet-derived growth factor was negatively correlated with inflammatory biomarkers. Patients ≥65 years had significantly higher levels of LDH and seven cytokines/chemokines (granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin IL-1b, IL-6, IL-10, IL-11, macrophage inflammatory protein (MIP)-1d, and IL-8) while levels of five other immune molecules (intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein 1 (MCP-1), tissue inhibitor of metalloproteinase 2 (TIMP-2), IL-2, and IL-4) were significantly lower compared to those <65 years. Females had significantly higher levels of LDH and 10 cytokines/chemokines (GM-CSF, IL-1b, IL-6, IL-10, IL-11, IL-15, IL-16, MIP-1a, MIP-1d, and IL-8) while levels of TIMP-2 and IL-4 were significantly lower than male patients. Conclusions The clinical characteristics of this rural cohort of hospitalized patients differed somewhat from nationally reported data. The contributions of social, environmental, and healthcare access factors should be investigated. We identified age and sex-associated differences in immunological response markers that warrant further investigation to identify the underlying molecular mechanisms and impact on COVID-19 pathogenesis.

Periodontal pathogens and cancer development.

Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti-apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.

The changes and the potential clinical applications of cytokines in Taiwan's major venomous snakebites patients.

BACKGROUND: Taiwan habu (Protobothrops mucrosquamatus), green bamboo viper (Viridovipera stejnegeri), and Taiwan cobra (Naja atra) are the most venomous snakebites in Taiwan. Patients commonly present with limb swelling but misdiagnosis rates are high, and currently available diagnostic tools are limited. This study explores the immune responses in snakebite patients to aid in differential diagnosis. METHODS: This prospective observational study investigated the changes in cytokines in snakebite patients and their potential for diagnosis. RESULTS: Elevated pro-inflammatory cytokines IL-6 and TNF-α were observed in all snakebite patients compared to the healthy control group. While no significant disparities were observed in humoral immune response cytokines, there were significant differences in IFN-γ levels, with significantly higher IL-10 levels in patients bitten by cobras. Patients with TNF-α levels exceeding 3.02 pg/mL were more likely to have been bitten by a cobra. CONCLUSION: This study sheds light on the immune responses triggered by various venomous snakebites, emphasizing the potential of cytokine patterns for snakebite-type differentiation. Larger studies are needed to validate these findings for clinical use, ultimately improving snakebite diagnosis and treatment.

Coexistence of nonfluorescent chromoproteins and fluorescent proteins in massive Porites spp. corals manifesting a pink pigmentation response.

Introduction: Several fluorescent proteins (FPs) and chromoproteins (CPs) are present in anthozoans and play possible roles in photoprotection. Coral tissues in massive corals often display discoloration accompanied by inflammation. Incidences of the pink pigmentation response (PPR) in massive Porites, described as inflammatory pink lesions of different shapes and sizes, has recently increased worldwide. FPs are reported to be present in PPR lesions, wherein a red fluorescent protein (RFP) appears to play a role in reducing reactive oxygen species. However, to date, the biochemical characterization and possible roles of the pigments involved are poorly understood. The present study aimed to identify and characterize the proteins responsible for pink discoloration in massive Porites colonies displaying PPRs, as well as to assess the differential distribution of pigments and the antioxidant properties of pigmented areas. Method: CPs were extracted from PPR lesions using gel-filtration chromatography and identified via genetic analysis using liquid chromatography-tandem mass spectrometry. The coexistence of CPs and RFP in coral tissues was assessed using microscopic observation. Photosynthetic antivity and hydrogen peroxide-scavenging activitiy were measured to assess coral stress conditions. Results: The present study revealed that the same CP (plut2.m8.16902.m1) isolated from massive Porites was present in both the pink spot and patch morphologies of the PPR. CPs were also found to coexist with RFP in coral tissues that manifested a PPR, with a differential distribution (coenosarc or tip of polyps' tentacles). High hydrogen peroxide-scavenging rates were found in tissues affected by PPR. Discussion and Conclusion: The coexistence of CPs and RFP suggests their possible differential role in coral immunity. CPs, which are specifically expressed in PPR lesions, may serve as an antioxidant in the affected coral tissue. Overall, this study provides new knowledge to our understanding of the role of CPs in coral immunity.

Severity of papular urticaria in children is associated with specific IgG4 anti-salivary gland antigens from Aedes aegypti.

Summary: Background. Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. Methods. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. Results. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). Conclusion. It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.

Lymphotoxin ß receptor and tertiary lymphoid organs shape acute and chronic allograft rejection.

Solid organ transplantation remains the life-saving treatment for end-stage organ failure, but chronic rejection remains a major obstacle to long-term allograft outcomes and has not improved substantially. Tertiary lymphoid organs (TLO) are ectopic lymphoid structures that form under conditions of chronic inflammation, and evidence from human transplantation suggests that TLO regularly form in allografts undergoing chronic rejection. In this study, we utilized a mouse renal transplantation model and manipulation of the lymphotoxin alpha (LTα) - lymphotoxin beta receptor (LTßR) pathway, which is essential for TLO formation, to define the role of TLO in transplantation. We showed that intragraft TLO are sufficient to activate the alloimmune response and mediate graft rejection in a model where the only lymphoid organs are TLO in the allograft. When transplanted to recipients with a normal set of secondary lymphoid organs, the presence of graft TLO or LTα overexpression accelerated rejection. If the LTßR pathway was disrupted in the donor graft, TLO formation was abrogated, and graft survival prolonged. Intravital microscopy of renal TLO demonstrated that local T and B cell activation in TLOs is similar to that observed in secondary lymphoid organs. In summary, we demonstrated that immune activation in TLO contributes to local immune responses, leading to earlier allograft failure. TLO and the LTαß-LTßR pathway are therefore prime targets to limit local immune responses and prevent allograft rejection. These findings are applicable to other diseases such as autoimmunity or tumors, where either limiting or boosting local immune responses is beneficial and improves disease outcomes.

Exploring the midgut physiology of the non-haematophagous mosquito Toxorhynchites theobaldi.

Toxorhynchites mosquitoes have an exclusively phytophagous feeding habit as adults, which leads to significant differences in their morphophysiology compared with haematophagous mosquitoes. However, the molecular mechanisms of digestion in this mosquito are not well understood. In this study, RNA sequencing of the posterior midgut (PMG) of the mosquito Toxorhynchites theobaldi was undertaken, highlighting its significance in mosquito digestion. Subsequently, a comparison was made between the differential gene expression of the PMG and that of the anterior midgut. It was found that the most abundant proteases in the PMG were trypsin and chymotrypsin, and the level of gene expression for enzymes essential for digestion (such as serine protease, α-amylase and pancreatic triacylglycerol lipase) and innate immune response (including catalase, cecropin-A2 and superoxide dismutase) was like that of haematophagous mosquitoes. Peritrophin-1 was detected in the entire midgut, with an elevated expression level in the PMG. Based on our findings, it is hypothesized that a non-haematophagic habit might have been exhibited by the ancestor of Tx. theobaldi, and this trait may have been retained. This study represents a pioneering investigation at the molecular level of midgut contents in a non-haematophagous mosquito. The findings offer valuable insights into the evolutionary aspects of feeding habits in culicids.

Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study.

There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.

The systemic cellular immune response against allogeneic mesenchymal stem cells is influenced by inflammation, differentiation and MHC compatibility: in vivo study in the horse.

The effectiveness and safety of allogeneic mesenchymal stem/stromal cells (MSCs) can be affected by patient's immune recognition. Thus, MSC immunogenicity and their immunomodulatory properties are crucial aspects for therapy. Immune responses after allogeneic MSC administration have been reported in different species, including equine. Interactions of allogenic MSCs with the recipient's immune system can be influenced by factors like matching or mismatching for the major histocompatibility complex (MHC) between donor-recipient, and by the levels of MHC expression in MSCs. The latter can vary upon MSC inflammatory exposure or differentiation, such as chondrogenic induction, making both priming and differentiation interesting therapeutic strategies. This study investigated the systemic in vivo immune cellular response against allogeneic equine MSCs in these situations. Either MSCs in basal conditions (MSC-naïve), pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were repeatedly administered subcutaneously into autologous, MHC-matched or MHC-mismatched allogeneic equine recipients. At different time-points after each administration, lymphocytes were obtained from recipient horses and exposed in vitro to the same type of MSCs to assess the proliferative response of different T cell subsets (cytotoxic, helper, regulatory), B cells, and interferon gamma (IFNγ) secretion. Higher proliferative response of helper and cytotoxic T lymphocytes and IFNγ secretion was observed in response to all types of MHC-mismatched MSCs over MHC-matched ones. MSC-primed produced the highest immune response, followed by MSC-naïve, and MSC-chondro. However, MSC-primed activated Treg and had a mild effect on B cells, and the response after their second administration was similar to the first one. On the other hand, both MSC-chondro and MSC-naïve barely induced Treg response but promoted B lymphocyte activation, and proportionally induced a higher cell response after the second administration. In conclusion, both the type of MSC conditioning and the MHC compatibility influenced systemic immune recognition of equine MSCs after single and repeated administrations, but the response was different. Selecting MHC-matched donors would be particularly recommended for MSC-primed and repeated MSC-naïve administrations. While MHC-mismatching in MSC-chondro would be less critical, B cell response should not be ignored. Comprehensively investigating the in vivo immune response against equine allogeneic MSCs is crucial for advancing veterinary cell therapies.

Combined immunogenicity evaluation for a new single-dose live-attenuated chikungunya vaccine.

BACKGROUND: Chikungunya is a serious and debilitating viral infection with a significant disease burden. VLA1553 (IXCHIQ®) is a live-attenuated vaccine licensed for active immunization for prevention of disease caused by chikungunya virus (CHIKV). METHODS: Immunogenicity following a single dose of VLA1553 was evaluated in healthy adults aged ≥18 years in two Phase 3 trials (N = 656 participants [per protocol analysis set]). Immunogenicity data to 180 days post-vaccination (geometric mean titers [GMTs], seroresponse rate, seroconversion rate) were pooled for the two trials. A comparison of subgroups based on age, sex, body mass index (BMI), race, and baseline seropositivity was included. All analyses were descriptive. RESULTS: Most participants were aged 18-64 years (N = 569/656 [86.7%]), there were slightly more females (N = 372/656 [56.7%]), most were not Hispanic/Latino (N = 579/656 [88.3%]), and most were White (N = 517/656 [78.8%]). In baseline seronegative participants, GMT peaked at Day 29 post-vaccination, and subsequently declined slightly but remained elevated until Day 180. At Days 29, 85, and 180, seroresponse rate was 98.3%, 97.7%, and 96.4% and seroconversion rate was 98.5%, 98.4%, and 98.2%. There were no differences in seroresponse rate in participants aged 18-64 years or ≥ 65 years at Day 29 (98.1% versus 100%), Day 85 (97.4% versus 100%), and Day 180 (96.3% versus 96.5%) nor based on sex, BMI, ethnicity, or race. An immune response was shown in a small heterogenous population of baseline seropositive participants, with GMTs showing the same trend as baseline seronegative participants. CONCLUSIONS: A single dose of VLA1553 elicited a very strong immune response by Day 29 that remained elevated at Day 180 in both baseline seronegative and seropositive participants in a combined evaluation of two Phase 3 trials. The vaccine was similarly immunogenic in participants aged ≥65 years and 18-64 years, and there were no differences based on subgroup analyses for sex, BMI, ethnicity, or race.

Possibility and challenge of plant-derived ferritin cages encapsulated polyphenols in the precise nutrition field.

Polyphenols have attracted extensive attention due to their rich functional activities, such as antioxidant, anti-inflammatory and anti-tumor. However, the low solubility and poor stability limit their bioavailability and functional activities. Plant-derived ferritin cages have a unique hollow cage structure that can embed polyphenols to improve their unfavorable properties. Therefore, it is essential to adequately elaborate and summarize plant-derived ferritin cages to maximize their potential benefits in nutritional interventions. This review focuses on the fundamental properties of plant-derived ferritin cages, including the preparation process, purification technology, identification methods, and structural and functional properties. The relevant research on ferritin cages in polyphenol delivery has been summarized, including the delivery of water/lipid soluble polyphenols, modification of ferritin cages, and the interaction between polyphenols and ferritin cages. The research progress, shortcomings and prospects of plant-derived ferritin cages in precise nutrition are introduced. In addition, the relevant research on ferritin in immune response and protein engineering is also discussed to provide the theoretical basis for applying plant-derived ferritin cages in many frontier fields.

Morphomolecular identification of heavy parasitic typhlitis in layer flocks: tissue response and cell-mediated reaction.

BACKGROUND: Heterakis gallinarum (H. gallinarum) is a common poultry parasite that can be found in the ceca of many gallinaceous bird species, causing minor pathology and reduced weight gain. Most infections go unnoticed in commercial flocks due to the dependence on fecal egg counts, which are prone to false-negative diagnoses. Furthermore, there is a lack of research on gastrointestinal nematodes that use molecular identification methods, which could be essential for rapid diagnosis and developing efficient control approaches. As a result, the study aimed to look at the cause of mortality in layer chickens induced by H. gallinarum in Egyptian poultry farms using morphological, ultrastructural, and molecular characterization. Histopathological, immunohistochemical, and cell-mediated immune responses from damaged cecal tissues were also examined. RESULTS: Seventy bird samples from ten-layer flocks of different breeds (Native, white, and brown layers) suffering from diarrhea, decreased egg output, and emaciation were collected. Cecal samples were collected from affected and non-affected birds and were examined for parasitic diseases using light and a scanning electron microscope. The mitochondrial cytochrome oxidase 1 (COX1) gene was used to characterize H. gallinarum. Our results showed that the collected nematodal worms were identified as H. gallinarum (male and female), further confirmed by COX1 gene amplification and sequence alignment. Gene expression analysis of the inflammatory markers in infected tissues showed a significant up-regulation of IL-2, IFN-γ, TLR-4, and IL-1ß and a significant down-regulation of the anti-inflammatory IL-10. The mRNA level of the apoptotic cas-3 revealed apoptotic activity among the H. gallinarum samples compared to the control group. CONCLUSIONS: Our results implemented the use of molecular methods for the diagnosis of Heterakis, and this is the first report showing the tissue immune response following infection in layers: upregulation of IL-1ß, IFN-γ, Il-2, and TLR-4, while down-regulation of anti-inflammatory IL-10 in cecal tissue, Cas-3 apoptotic activity and Nuclear factor-κB (NF-κB)activity with immunophenotyping of T-cells in Heterakis infected tissue.

RNA editing landscape of adipose tissue in polycystic ovary syndrome provides insight into the obesity-related immune responses.

Background: Polycystic ovary syndrome (PCOS) is the most common reproductive-endocrine disorder with wide-ranging metabolic implications, including obesity. RNA editing, a post-transcriptional modification, can fine-tune protein function and introduce heterogeneity. However, the role of RNA editing and its impact on adipose tissue function in PCOS remain poorly understood. Methods: This study aimed to comprehensively analyze RNA-editing events in abdominal and subcutaneous adipose tissue of PCOS patients and healthy controls using high-throughput whole-genome sequencing (WGS) and RNA sequencing. Results: Our results revealed that PCOS patients exhibited more RNA-editing sites, with adenosine-to-inosine (A-to-I) editing being prevalent. The expression of ADAR genes, responsible for A-to-I editing, was also higher in PCOS. Aberrant RNA-editing sites in PCOS adipose tissue was enriched in immune responses, and interleukin-12 biosynthetic process. Tumor necrosis factor (TNF) signaling, nuclear factor kappa B (NF-κB) signaling, Notch signaling, terminal uridylyl transferase 4 (TUT4), hook microtubule tethering protein 3 (HOOK3), and forkhead box O1 (FOXO1) were identified to be of significant differences. Differentially expressed genes (DEGs) in PCOS adipose tissue were enriched in immune responses compared with controls, and the DEGs between subcutaneous and abdominal adipose tissue were also enriched in immune responses suggesting the important role of subcutaneous adipose tissue. Furthermore, we identified the correlations between RNA editing levels and RNA expression levels of specific genes, such as ataxia-telangiectasia mutated (ATM) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) in inflammation pathways and ATM, TUT4, and YTH N6-methyladenosine RNA-binding protein C2 (YTHDC2) in oocyte development pathway. Conclusions: These findings suggest that RNA-editing dysregulation in PCOS adipose tissue may contribute to inflammatory dysregulations. Understanding the interplay between RNA editing and adipose tissue function may unveil potential therapeutic targets for PCOS management. However, further research and validation are required to fully elucidate the molecular mechanisms underlying these associations.

Biphasic bone substitutes coated with PLGA incorporating therapeutic ions Sr2+ and Mg2+: cytotoxicity cascade and in vivo response of immune and bone regeneration.

The incorporation of bioactive ions into biomaterials has gained significant attention as a strategy to enhance bone tissue regeneration on the molecular level. However, little knowledge exists about the effects of the addition of these ions on the immune response and especially on the most important cellular regulators, the macrophages. Thus, this study aimed to investigate the in vitro cytocompatibility and in vivo regulation of bone remodeling and material-related immune responses of a biphasic bone substitute (BBS) coated with metal ions (Sr2+/Mg2+) and PLGA, using the pure BBS as control group. Initially, two cytocompatible modified material variants were identified according to the in vitro results obtained following the DIN EN ISO 10993-5 protocol. The surface structure and ion release of both materials were characterized using SEM-EDX and ICP-OES. The materials were then implanted into Wistar rats for 10, 30, and 90 days using a cranial defect model. Histopathological and histomorphometrical analyses were applied to evaluate material degradation, bone regeneration, osteoconductivity, and immune response. The findings revealed that in all study groups comparable new bone formation were found. However, during the early implantation period, the BBS_Sr2+ group exhibited significantly faster regeneration compared to the other two groups. Additionally, all materials induced comparable tissue and immune responses involving high numbers of both pro-inflammatory macrophages and multinucleated giant cells (MNGCs). In conclusion, this study delved into the repercussions of therapeutic ion doping on bone regeneration patterns and inflammatory responses, offering insights for the advancement of a new generation of biphasic calcium phosphate materials with potential clinical applicability.

Impact of adding zeolite to broilers' diet and litter on growth, blood parameters, immunity, and ammonia emission.

This work was designed to assess the impact of varying zeolite concentrations in diet and litter to enhance broiler's growth performance, immunity, and litter quality. A complete random arrangement was used for distributing 525 unsexed "Cobb 500" broiler chicks into seven treatments (75 chick / treatment), each treatment divided into 3 replicates (25 chicks / replicate). The 1st group (control one) received the recommended basal diet. Zeolite has been introduced to the basal diet (ZD) of the second, third, and fourth groups at concentrations of 5, 10, and 15 g/kg, respectively. The 5th, 6th and 7th groups used zeolite mixed with litter (ZL) at 0.5, 1, and 1.5 kg/m2 of litter, respectively. Due to the obtained results, adding zeolite with levels 15 g/kg of diet and 1.5 kg/1 m2 of litter, a significant improvement occurred in live body weight (LBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR) and European production efficiency factor (EPEF). Also, transaminase enzymes (ALT and AST), creatinine, white blood cells (WBCs) and different Immunoglobulins were significantly increased with different zeolite levels, except urea concentrations which showed reduced due to different zeolite treatments. In addition, spleen relative weight hasn't been affected by zeolite treatments, even though thymus and bursa relative weights had been affected significantly. Moreover, the antibodies' production to Newcastle disease virus (NDV) and Avian influenza virus (AIV) had increased significantly with adding zeolite with levels 10 g/kg of diet and 1.5 kg/1m2 of litter. Litter quality traits (NH3 concentration, pH values, and Moisture content) were improved with zeolite addition. So, zeolite could be employed in both feed and litter of broilers to maximize their production, immunity and improve farm's climate.

Reduced cell-mediated immune response in hyperglycemic NOD mice following influenza vaccination.

Due to the higher risk of medical complications posed by influenza infection, patients with type 1 diabetes (T1D) are strongly recommended to receive the influenza vaccine. However, it remains unclear if hyperglycemia in patients with T1D affects vaccine-induced immune responses. In this study, we investigated the humoral and cellular immune responses of prediabetic and diabetic, nonobese diabetic (NOD) mice following influenza vaccination to determine the effects of hyperglycemia on influenza vaccine-induced responses. In diabetic NOD mice, vaccine-specific IgG and IgM levels, as well as IgG-producing cells, were comparable to those in prediabetic NOD mice. However, the diabetic NOD mice exhibited reduced percentages of memory T cells and activated T cells in the spleen, along with reduced number of vaccine-specific interferon (IFN)-γ-secreting cells. Thus, these findings suggest that in patients with T1D, hyperglycemia could lead to impaired cell-mediated immune responses following influenza vaccination.

Advances in virus-like particle-based SARS-CoV-2 vaccines.

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has incurred devastating human and economic losses. Vaccination remains the most effective approach for controlling the COVID-19 pandemic. Nonetheless, the sustained evolution of SARS-CoV-2 variants has provoked concerns among the scientific community regarding the development of next-generation COVID-19 vaccines. Among these, given their safety, immunogenicity, and flexibility to display varied and native epitopes, virus-like particle (VLP)-based vaccines represent one of the most promising next-generation vaccines. In this review, we summarize the advantages and characteristics of VLP platforms, strategies for antigen display, and current clinical trial progress of SARS-CoV-2 vaccines based on VLP platforms. Importantly, the experience and lessons learned from the development of SARS-CoV-2 VLP vaccines provide insights into the development of strategies based on VLP vaccines to prevent future coronavirus pandemics and other epidemics.