Immunity Test Research Articles

The effect of carbon nanoparticles vs. immune colloidal gold technique test strips on parathyroid protection in total thyroidectomy: A randomized clinical trial study.

The long-term effect of intraoperative usage of carbon nanoparticles (CN) and parathyroid hormone (PTH) test strip using immune colloidal gold technique (ICGT) is unclear. This study aims to compare the effect of intraoperative usage of CN and ICGT test strips on PG function. This randomized clinical study involved adult patients who underwent total thyroidectomy. They were randomly allocated into three groups (control, CN, and ICGT group). Clinical data were analyzed. Each group involved 98 patients. Serum calcium and PTH concentrations at 24 h postoperatively (PTH24h) were higher in CN group. The parathyroid function recovered quicker in CN group. Use of CN increased in situ PG preservation and PTH24h. Mediation analysis indicated that 23.05% of the total effect of CN on PTH24h was attributed to PGRIS. CN holds promise to improve in situ PG preservation and protect PG vasculature, thereby reducing the incidence of early hypoparathyroidism. The value of ICGT test strips for PG protection is dubious.

Rare FLG mutation associated with severe atopy

Background: The prevalence of atopic disease, which consists of conditions such as atopic dermatitis, allergies, and asthma, has been on the rise in recent decades. In children, atopic dermatitis often acts as an initial manifestation of atopic disease and frequently precedes the development of food allergies, asthma, and allergic rhinitis. Mutations in the FLG gene, encoding the fillagrin precursor profillagrin, serve as a genetic risk factor for these diseases. Approximately 25%–50% of individuals with atopic dermatitis carry FLG mutations. It has been proposed that FLG mutations exhibit variations specific to different populations, indicating distinct patterns within each population. Severe allergic symptoms could indicate the presence of an underlying immunodeficiency or immune dysregulation and in patients with severe, early-onset, or simultaneous allergic conditions, these could be suggestive of an underlying Primary Atopic Disorder. Specifically, the allergic triad characterized by elevated IgE levels, eosinophilia, and eczema is a common feature in various inborn errors of immunity that could be mistakenly diagnosed as severe allergic conditions. Method: Our patient’s medical record was analyzed retrospectively, including her medical history, as well as results from immune laboratory tests and genetic analyses. Results: We present a 9-year-old female of mixed ethnicity with a history severe eczematous rash diagnosed with atopic dermatitis. Whole exome sequencing analysis revealed an initially novel heterozygous variant in the FLG gene (NM_002016: EXON3:c.C2218T: p.R740X). Conclusion: Healthcare providers caring for patients with atopic dermatitis and recurrent staphlococcus infections should be aware of the significant link between filaggrin gene mutations and the development of severe, persistent atopic dermatitis that begins in childhood, as well as its association with recurring staphlococcus infections. Additionally, they should keep in mind that certain inborn errors of immunity may predominantly manifest as severe and treatment-resistant atopic disorders. Statement of novelty: We have identified a rare variant in the FLG gene associated with severe atopic dermatitis and allergies.

Principles and features of ultrasound hypoechogenicity in diffuse thyroid pathology.

For different thyroid diseases and hormonal metabolism, ultrasound (US) of the thyroid gland reveals hypoechogenicity. Despite the direct correlation of hypoechogenicity with the levels of thyroid-stimulating hormone and antibodies of thyroid peroxidase and thyroglobulin, ~20% of this correlation is inconsistent, thus restricting the comprehensive utilisation of this valuable diagnostic sign. Thus, it is necessary to investigate the additional circumstances affecting the extent and features of the US hypoechogenicity of the thyroid gland. The technique for assessing thyroid hypoechogenicity was based on the basic setting of the US mode and visual assessment in percentage of gray relative to a gradient gray scale. Doppler mode was used. US data were compared with the results of hormonal and immune blood tests. The study contains the morphofunctional basis of the various US hypoechogenicities detected in the diffuse pathology of the thyroid gland has been presented, and the principles and probable mechanisms of widespread and segmental hypoechogenicity formation are disclosed for the first time. Furthermore, a mandatory Doppler involving thyroid parenchyma blood flow intensity and peak systolic blood velocity of thyroid arteries, which indicates the magnitude of neurovegetative influence, has been suggested. The results of the study shows revealed that the evaluation of the importance and features of US hypoechogenicity in various diffuse thyroid pathologies is probably based on a single system involving neurohumoral regulation, segmental arrangement and compensatory reserve state of the gland parenchyma.

Analysis of characteristic and postexposure practices of occupational blood and body fluid exposures among health care workers in Chinese tertiary hospitals: a retrospective ten-year study

BackgroundOccupational blood and body fluid exposure (OBEs) is a highly concerning global health problem in health facilities. Improper or inadequate post-exposure practices increase the risk of infection with bloodborne pathogens. Understanding risk factors for OBEs and evaluating the post-exposure practices will contribute to healthcare workers’ (HCWs) well-being.MethodsThis study retrospectively synthesized and reviewed the 10-year data (from 2010 to 2020) on OBEs in a tertiary teaching hospital.ResultsA total of 519 HCWs have reported OBEs, increasing yearly from 2010 to 2020. Of these, most were nurses (247 [47.2%]), female (390 [75.1%]), at 23–27 years old (207 [39.9%]). The hepatitis B was the primary bloodborne pathogen exposed to HCWs, with 285 (54.9%) cases, internal medicine was the main exposure site (161 [31.0%]), and sharp injury was the main exposure route (439 [84.6%]). Data analysis shows that there are significant differences between exposure route, exposed pathogens, and exposure site among the different occupational categories (X2 = 14.5, 43.7, 94.3, all P < 0.001). 3.3% of HCWs did not take any post-exposure practices. For percutaneous exposure, 4.7% did not rinse the wound, 3.3% did not squeeze out the wound, and 2.3% did not disinfect the wound. In the case of mucosal exposure, 90.4% clean the exposure area immediately.ConclusionsThe data from the past decade underscores the seriousness of current situation of OBEs in Chinese tertiary hospital, particularly among young HCWs, and with hepatitis B as the predominant blood-borne pathogen. This study also identifies HCWs may take incorrect post-exposure practices. It’s crucial in the future to discuss the effectiveness of main groups targeted for focused specialty-specific guidance for the prevention of such accidents, meanwhile, to include blood-borne disease immunity testing in mandatory health check-ups. Additionally, focus on optimizing post-exposure practices, offering significant steps toward prevention of such incidents and reducing infection risks should also be considered in future studies.

Risk Assessment for Workers with Wearable Medical Devices Exposed to Electromagnetic Fields.

The exponential diffusion of wearable medical devices (WMD) in recent years has involved people of all ages, including workers. Workers who use WMDs should be considered at a particular risk from electromagnetic fields, and in accordance with EU Directive 2013/35/EU, they require an individual risk assessment. Currently, there is no international standard that provides specific guidance on how to perform such a risk assessment. This paper focuses on the effects of electromagnetic fields on WMDs and does not consider the direct effects on human body tissues. It aims to offer practical recommendations to employers and/or health physicists for the risk assessment of workers with WMDs. Focusing on EU countries, we first describe the requirements outlined by the technical standard for the electromagnetic compatibility (EMC) of medical electrical equipment EN 60601-1-2. Then, some general guidelines on how to perform the risk assessment are provided. The assessment can be conducted by comparing the field values measured in the workplace with the immunity test levels specified in the technical standards of medical electrical equipment. If the measured values are lower than the immunity test levels indicated in the standard and the distance from the electromagnetic source is greater than the distance used by the manufacturer during the EMC (electromagnetic compatibility) tests (typically 30 cm), the risk for the worker may be considered acceptable. However, if the measured values exceed the immunity test levels or the distance criteria, a specific evaluation based on a case-by-case analysis is required.

A237 ROTAVIRUS VACCINE SAFETY IN INFANTS EXPOSED TO BIOLOGICS IN UTERO IN AN INFLAMMATORY BOWEL DISEASE POPULATION: A PROSPECTIVE COHORT STUDY

Abstract Background Biologics, the mainstay of therapy in patients with moderate-to-severe inflammatory bowel disease (IBD), undergo placental transfer during the second trimester of pregnancy and may remain detectable in the blood of exposed infants for up to 12 months. Due to concerns regarding the risk of immunosuppression and adverse events following immunization with live attenuated vaccines in infants exposed to biologics in utero, current guidelines recommend avoiding live vaccines in the first 6 to 12 months of life. Aims This study investigates whether the live rotavirus vaccine can safely be administered in infants exposed to biologics in utero. Methods We conducted a single-centre prospective cohort study, which included infants exposed to biologics in utero and born to mothers with IBD between October 1, 2020 and June 30, 2022. Infants were included in the study if they were assessed by Paediatric specialists at the Special Immunization Clinic (SIC) at SickKids Hospital (Toronto, Ontario). Mothers were followed by Gastroenterologists at the Special Pregnancy IBD Clinic at Mount Sinai Hospital (Toronto, Ontario). Data were collected on biologic agent exposure history, infant immune function testing, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunization. Adverse events following immunization included fevers, vomiting, diarrhea, and/or intussusception within 42 days following immunization. Results 22 infants were included in the study. Of the 22 infants, 5 (22.7%) were exposed to infliximab in utero, 10 (45.5%) were exposed to adalimumab, 3 (13.6%) were exposed to vedolizumab, and 3 (13.6%) were exposed to ustekinumab. Of the 22 infants, 18 (81.8%) were recommended to receive the rotavirus vaccine by the SIC. 1 (0.05%) was not recommended to receive the vaccine due to neutropenia and low CD54 count on lymphocyte testing. The recommendation given to 3 infants is unknown. Of the 18 infants who were recommended to receive the vaccine, 16 (88.9%) received the vaccine and had no adverse events following immunization. 1 (6%) infant did not receive the rotavirus vaccine despite it being recommended due to parental choice. The rotavirus vaccination status and response in 1 infant recommended to receive the vaccine, is unknown. Conclusions Administration of the rotavirus vaccine in biologic-exposed infants did not result in adverse events in our study cohort. Although guidelines currently advise against live vaccinations in infants exposed to biologics in utero, specialist assessment of infant immune function can help encourage safe live vaccination uptake. Funding Agencies None

A phase 2 study of the combination dostarlimab with niraparib in patients with penile carcinoma that has progressed following chemotherapy.

TPS13 Background: Penile squamous cell carcinoma (PSCC) is a rare and deadly cancer, with limited therapy options in patients with disease progressive on platinum chemotherapy. Patients are encouraged to enroll in clinical trials since the overall survival is less than 5 months with standard therapy. Development of efficacious treatment options for patients with chemotherapy refractory PSCC, remains an unmet need. Preclinical work suggests synergic activity between PARP inhibitors and immune checkpoint inhibitors in PSCC animal models. The niraparib plus dostarlimab combination may generate a robust antitumor immune response in cisplatin refractory patients with PSCC. Methods: This is an open-label, multi-center, Simon 2 stage design, phase 2 study to evaluate the efficacy and safety of the combination of niraparib and dostarlimab in patients with advanced relapsed/refractory PSCC. Patients must provide a sufficient tumor tissue sample for molecular and immune testing at screening. Blood samples will be collected at C1D1 for exploratory molecular testing, at C3D1 and at the time of investigator-assessed partial response (PR) or complete response (CR), and at the end of treatment visit. Niraparib at 200 mg daily will be administered orally once daily on days 1 to 21 and dostarlimab intravenously once every three weeks for cycles 1 to 4 and once every 6 weeks thereafter. Niraparib will be administered at 200 mg, oral, once daily, from days 1 through 21 until progression of disease or toxicity. Eligible patients must have histologically confirmed stage III (unresectable) or stage IV penile cancer according to the American Joint Committee on Cancer (AJCC) staging system, have had progression of disease or poor tolerance to one line of platinum therapy, have a life expectancy of more than 12 weeks, have an ECOG PS of 0 or 1 (ECOG PS 2 can be included after discussion with PI), measurable disease per Immune-Modified Response Evaluation Criteria in Solid Tumors iRECIST, adequate organ function, and must not have received any prior immuno-oncology regimens, cancer vaccines, adoptive cell therapies, or other cytokine therapies. The primary efficacy endpoint is Investigator-assessed confirmed overall response rate (ORR). Tumor response will be evaluated using iRECIST. Patients who receive at least 1 complete dose of either study drug will be considered evaluable for response. The secondary endpoints are to estimate the progression free survival (PFS) overall survival measured duration of Response (DOR) and to evaluate the safety and tolerability of the niraparib and dostarlimab combination in patients with PSCC. Six patients of the 25-patient target enrollment have been enrolled. Clinical trial information: NCT05526989 .

Depth acquisition from dual-frequency fringes based on end-to-end learning

The end-to-end networks have been successfully applied in fringe projection profilometry in recent years for their high flexibility and fast speed. Most of them can predict the depth map from a single fringe. But the depth map inherits the fringe fluctuation and loses the local details of the measured object. To address this issue, an end-to-end network based on double spatially frequency fringes (dual-frequency based depth acquisition network) is proposed. To release the periodic error of the predicted depth map, a dual-branch structure is designed to learn the global contour and local details of the measured object from dual-frequency patterns. To fully exploit the contextual information of the fringe patterns, five novel modules are proposed to accomplish feature extraction, down-sampling/up-sampling, and information feeding. Ablation experiments verify the effectiveness of the presented modules. Competitive experiments demonstrate that the proposed lightweight network presents higher accuracy compared to the existing end-to-end learning algorithms. Noise immunity test and physical validation demonstrate the generalization of the network.

Excess risk of COVID-19 infection and mental distress in healthcare workers during successive pandemic waves: Analysis of matched cohorts of healthcare workers and community referents in Alberta, Canada

ObjectivesTo investigate changes in risk of infection and mental distress in healthcare workers (HCWs) relative to the community as the COVID-19 pandemic progressed.MethodsHCWs in Alberta, Canada, recruited to an interprovincial cohort, were asked consent to link to Alberta’s administrative health database (AHDB) and to information on COVID-19 immunization and polymerase chain reaction (PCR) testing. Those consenting were matched to records of up to five community referents (CRs). Physician diagnoses of COVID-19 were identified in the AHDB from the start of the pandemic to 31 March 2022. Physician consultations for mental health (MH) conditions (anxiety, stress/adjustment reaction, depressive) were identified from 1 April 2017 to 31 March 2022. Risks for HCW relative to CR were estimated by fitting wave-specific hazard ratios.ResultsEighty percent (3050/3812) of HCWs consented to be linked to the AHDB; 97% (2959/3050) were matched to 14,546 CRs. HCWs were at greater risk of COVID-19 overall, with first infection defined from either PCR tests (OR=1.96, 95%CI 1.76–2.17) or physician records (OR=1.33, 95%CI 1.21–1.45). They were also at increased risk for each of the three MH diagnoses. In analyses adjusted for confounding, risk of COVID-19 infection was higher than for CRs early in the pandemic and during the fifth (Omicron) wave. The excess risk of stress/adjustment reactions (OR=1.52, 95%CI 1.35–1.71) and depressive conditions (OR=1.39, 95%CI 1.24–1.55) increased with successive waves during the epidemic, peaking in the fourth wave.ConclusionHCWs were at increased risk of both COVID-19 and mental ill-health with the excess risk continuing late in the pandemic.

A modular and scalable system for electromagnetic compatibility testing of integrated circuits

To bring automotive integrated circuits (ICs) to market, manufacturers must subject their products to numerous electromagnetic compatibility (EMC) tests such as electromagnetic immunity and emission tests, or electrostatic discharge (ESD) tests. These tests need EMC test boards that meet the requirements of the specific standards. However, the current need to increase the frequency range of EMC tests poses a challenge in designing standard-compliant test boards. In this paper, we address this issue by introducing a modular and reusable IC level EMC test system. We demonstrate the system’s effectiveness with an example of two frequently used and conducted EMC tests: the direct power injection (DPI) immunity test and the 150Ω\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$150\\,\\mathrm{\\Omega}$$\\end{document} electromagnetic emission measurement. The two test setups are constructed and validated using the presented modules. It is shown how the frequency range can be expanded while minimizing costs and design efforts for the EMC test board design.

Country-Specific Screening, Prevalence, and Immunity Rates for Hepatitis B Infection in a Large US Safety-Net System.

Country- and region-specific estimates of hepatitis B virus (HBV) screening, prevalence, and immunity rates are provided for 202 868 adults from 174 unique countries in a large urban safety-net system. Of these, 41.8% (95% confidence interval, 41.5%-42.0%) were screened, with age-adjusted HBV prevalence of 0.9% (.9%-1.0%); 55.3% (54.9%-55.7%) had immunity testing, and 32.4% (31.9%-33.0%) were immune.

Contriving a novel multi-epitope subunit vaccine from Plasmodium falciparum vaccine candidates against malaria

In this study, immunoinformatics strategies were used to design a subunit vaccine against malaria from immunogenic regions of three Plasmodium falciparum surface antigens; liver stage antigen 3-C (V750-K1433), merozoite surface antigen 180 truncate-4 (A805-P1093), and merozoite surface protein 10 region 1 (D29-N188). A multi-epitope subunit vaccine construct (VC) was designed from immunodominant B- and T-cell epitopes followed by structure prediction, evaluation, and validation. Toll-like receptors (TLRs) 2 and 4 were docked with the VC. Their complexes’ molecular dynamics, immune stimulation, codon optimization, and in silico cloning of the VC were simulated. The VC is a 49.2 kDa antigenic and nonallergenic protein, comprised of 26% α-helix, 7% β-strand, 66% coil. The immune simulation test showed that the vaccine could provoke adaptive immune responses, and molecular docking tests showed that it interacts strongly with TLR-2 (−945.1 kcal/mol) and TLR-4 (−919.8 kcal/mol) to form complexes of high stability that hardly deform. The guanine-cytosine content and codon adaptation index of the VC were 42.94 and 0.99 after codon optimization. Escherichia coli pET-28a(+) was identified as the best vector for optimal gene expression. In conclusion, the study reveals that the VC shows promising results in neutralizing falciparum malaria.

Methods for Analysis of Nanoparticle Immunosuppressive Properties.

Adverse drug effects on immune system function represent a significant concern in the pharmaceutical industry, because 10-20% of drug withdrawal from the market is attributed to immunotoxicity. Immunosuppression is one such adverse effect. The traditional immune function test used to estimate materials' immunosuppression is T cell dependent antibody response (TDAR). This method involves a 28-day in vivo study evaluating the animal's antibody titer to a known antigen (Keyhole Limpet Hemocyanin; KLH) with and without challenge. Due to the limited quantities of novel drug candidates, an in vitro method called human lymphocyte activation (HuLA) assay has been developed to substitute the traditional TDAR assay during early preclinical development. In this test, leukocytes isolated from healthy donors vaccinated with the current year's flu vaccine are incubated with Fluzone in the presence or absence of nanoparticles. The antigen-specific lymphocyte proliferation is then measured by ELISA analyzing incorporation of BrdU into DNA of the proliferating cells. Here we describe the experimental procedures for investigating immunosuppressive properties of nanoparticles by both TDAR and HuLA assays, discuss the in vitro-in vivo correlation of these methods, and show a case study using the iron oxide nanoparticle formulation, Feraheme.

A 3D hanging spheroid-filter plate for high-throughput drug testing and CAR T cell cytotoxicity assay.

Tumour spheroids are widely used in immune cell cytotoxicity assays and anticancer drug testing, providing a physiologically relevant model replicating the tumour microenvironment. However, co-culture of immune and tumour cells complicates quantification of immune cell killing efficiency. We present a novel 3D hanging spheroid-filter plate that efficiently facilitates spheroid formation and separates unbound/dead cells during cytotoxicity assays. Optical imaging directly measures the cytotoxic effects of anti-cancer drugs on tumour spheroids, eliminating the need for live/dead fluorescent staining. This approach enables cost-effective evaluation of T-cell cytotoxicity with specific chimeric antigen receptors (CARs), enhancing immune cell-based assays and drug testing in three-dimensional tumour models.

Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is an important type of pathogenic bacteria that causes diarrhea in humans and young livestock. The pathogen has a high morbidity and mortality rate, resulting in significant economic losses in the pig industry. To effectively prevent piglet diarrhea, we developed a new tetravalent genetically engineered vaccine that specifically targets ETEC. To eliminate the natural toxin activity of ST1 enterotoxin and enhance the preventive effect of the vaccine, the mutated ST 1, K88ac, K99, and LT B genes were amplified by PCR and site-specific mutation techniques. The recombinant strain BL21(DE3)(pXKK3SL) was constructed and achieved high expression. Animal experiments showed that the inactivated vaccine had eliminated the natural toxin activity of ST1. The immune protection test demonstrated that the inclusion body and inactivated vaccine exhibited a positive immune effect. The protection rates of the inclusion body group and inactivated vaccine group were 96 and 98%, respectively, when challenged with 1 minimum lethal dose, indicating that the constructed K88ac-K99-3ST1-LTB vaccine achieved a strong immune effect. Additionally, the minimum immune doses for mice and pregnant sows were determined to be 0.2 and 2 mL, respectively. This study suggests that the novel K88ac-K99-3ST1-LTB vaccine has a wide immune spectrum and can prevent diarrhea caused by ETEC through enterotoxin and fimbrial pathways. The aforementioned research demonstrates that the K88ac-K99-3ST1-LTB vaccine offers a new genetically engineered vaccine that shows potential for preventing diarrhea in newborn piglets.

Identification and drug resistance of pathogen of ulcerative skin disease and its immune responses and protective efficacy after vaccination in a giant spiny frog, Quasipaa spinosa

ObjectiveIn order to explore the pathogen of the ulcerative skin disease in giant spiny frog (Quasipaa spinosa), and to provide theoretical basis for the prevention and control of the disease in practical production, this study was carried out to isolate and identify the pathogenic bacteria from the sick frogs suffering from rotting skin disease and to carry out the immunization test of the inactivated vaccine. MethodsPhysiological and biochemical characterization, and molecular biology of the pathogenic bacteria were identified, and drug screening and immunization responses were also carried out. ResultsThe dominant bacterium QS01 was isolated from the lesions of diseased giant spiny frogs, which was confirmed to be the causative agent of the rotting skin disease of giant spiny frogs by artificial regression infection test. Based on the fact that the pathogen is a gram-negative short bacterium, its phenotypic characteristics and 16S rRNA and gyrB gene sequences were analyzed, and the bacterium was determined to be Citrobacter freundii. The results of the drug sensitivity test showed that the bacterium was sensitive to 11 antibiotics, including Enrofloxacin, Fleroxacin and Ciprofloxacin, including three non-polluting drugs such as Florfenicol, Roxithromycin and Thiamphenicol, as well as three Chinese herbal medicines such as Rheum officinale Baill, Coptis chinensis Franch and Scutellaria baicalensis Georgi. Most non-specific immune responses could go to recovery in 24h. The frogs were vaccinated with QS01 formaldehyde inactivated vaccine by injection, immersion and spraying, and the serum antibody potency of the three immunized groups with the average potency reached the peak at the 20th d after immunization, and the serum antibody potency of the injected immunized group was at the highest ratio of 1:64–128 (101.6), while the immersed group and the spraying group attained the ratio of 1:16–32 (20.2) and 1:16–32 (16) respectively, and lasted until the 30th d. The control group that was not immunized had the highest serum antibody potency of 1:16–32 (20.2) and 1:16–32 (16), and continued until the 30th d. The control group that was not immunized was not immunized. The serum antibody potency of the unimmunized control group was 1:2 to 2(2). The immunoprotection rates after takedown were 100 %, 85.71 % and 71.43 %, respectively. ConclusionC. freundii is the pathogen of the disease in this farm, and the vaccination by immersion and spraying can effectively prevent and control the rotting skin disease in frogs. These results revealed pathogenicity of C. freundii and its activation of host immune response, which will provide a scientific reference for the aquaculture and disease prevention in Q. spinosa culture.

Changes in Early T-Cell Subsets and Their Impact on Prognosis in Patients with Sepsis: A Single-Center Retrospective Study.

To analyze the early changes in CD3+, CD4+, and CD8+T-cell subset counts in patients with sepsis and their correlation with prognosis to provide a feasible basis for clinical immunomodulation in sepsis. This is a single-center retrospective study. The study enrolled sepsis patients (meeting SEPSIS 3.0 definition) who were admitted to the Department of Intensive Care Unit at the First Hospital of Jilin University from July 5th, 2018 to December 5th, 2019 and were aged 18 years or above. In addition, these patients underwent cellular immune testing (CD3+, CD4+, CD8+ T lymphocyte counts, and CD4+/CD8+ ratio) within 24 hours of ICU admission. Patient's clinical data including age, gender, infection site, APACHE II score, SOFA score, length of ICU stay, mechanical ventilation time, ICU mortality, 28-day mortality, and 3-year survival status were collected. The prognostic indicators and survival of the decreased and nondecreased groups of different subsets of T lymphocyte counts and CD4+/CD8+ ratio were compared. A total of 206 patients were enrolled, with 76.7% having a decrease in CD3+ T lymphocyte count, 76.7% having a decrease in CD4+ T lymphocyte count, and 63.6% having a decrease in CD8+ T lymphocyte count. Furthermore, 21.8% had a lower CD4+/CD8+ ratio. Analysis showed that the CD3+ T lymphocyte count decreased group had a longer length of ICU stay [11 d (4, 21) vs. 7 d (4, 17), P=0.03], increased percentage of mechanical ventilation (67.5% vs. 51.0%, P=0.04), and extended mechanical ventilation time [144 h (48, 360) vs. 96 h (48, 144), P=0.04] compared to the nondecreased group. The 28-day mortality was higher in the decreased group of CD4+/CD8+ ratio compared to the nondecreased group (33.3% vs. 25.5%, P=0.29); however, the difference did not reach statistical significance. Logistic regression analysis revealed no significant correlation between the decrease in CD4+/CD8+ ratio and 28-day mortality (P=0.11). The 3-year follow-up revealed that the CD4+/CD8+ decreased group had a lower survival rate than the nondecreased group (33.3% vs. 53.4%, P=0.01). In the early stage of sepsis, most patients showed a decrease in CD3+, CD4+, and CD8+T-cell subsets, as well as in the CD4+/CD8+ ratio. The decrease in CD3+ and CD4+/CD8+ was related to some poor prognosis.

Evaluation of the humoral immunity in mice induced by foot-and-mouth disease virus-like particles-ZIF-8 complexes with different sizes

To further enhance the immune effect of the foot-and-mouth disease (FMD) virus-like particles (VLPs) vaccine, this study prepared FMDV VLPs-zeolitic imidazolate (framework-8, ZIF-8) complexes with different particle sizes. We used a biomimetic mineralization method with Zn2+ and 2-methylimidazole in different concentration ratios to investigate the effect of size on the immunization effect. The results showed that FMDV VLPs-ZIF-8 with three different sizes were successfully prepared, with an approximate size of 70 nm, 100 nm, and 1 000 nm, respectively. Cytotoxicity and animal toxicity tests showed that all three complexes exhibited excellent biological safety. Immunization tests in mice showed that all three complexes enhanced the titers of neutralizing and specific antibodies, and their immune effects improved as the size of the complexes decreased. This study showed that ZIF-8 encapsulation of FMDV VLPs significantly enhanced their immunogenic effect in a size-dependent manner.

Three-dimensional cell models for studying tumor–immune interactions and testing immunotherapeutic drugs

One of the most promising approaches to cancer treatment is immunotherapy. Suppression of immune checkpoints in tumor tissue (anti-CTLA4, anti-PD1) using monoclonal antibodies has increased the overall survival of patients with some forms of skin melanoma and lung cancer. However, the percentage of patients responding to treatment varies from 20% to 40% depending on the type of cancer and the expression of target molecules by the tumor. The main source of failure of immunotherapy is the tumor microenvironment, which affects both tumor cells and immune cells, causing them to adapt to immunotherapeutic drugs. It is known that the architecture and cellular composition of the microenvironment act on various tumor parameters, promoting the recruitment of immunosuppressive cells into the tumor tissue, as well as the expression of checkpoint inhibitors, such as PD-L1, by tumor cells. Therefore, the complex composition of the tumor microenvironment must be taken into account when searching for new therapies and stratifying patients who may respond to immunotherapy. Therefore, in immunooncological studies, it is necessary to use three-dimensional cellular models that more fully reflect the architecture and cellular composition of the tumor. In this review, we evaluate three-dimensional cell models as tools for research in the field of immuno-oncology, as well as for personalized treatment selection, the search for new targets, and the optimization of existing cancer immunotherapies.

Rapid and high throughput assessment of cellular immunity against SARS-CoV-2 based on the ex vivo activation of genes in leukocyte assay with whole blood

During the novel coronavirus outbreak and vaccine development, antibody production garnered major focus as the primary immunogenic response. However, cellular immunity's recent demonstration of comparable or greater significance in controlling infection demands the re-evaluation of the importance of T-cell immunity in SARS-CoV-2 infection. Here, we developed a novel assay, the ex vivo activation of genes in leukocytes (EAGL), which employs short-term whole blood stimulation with the LeukoComplete™ system, to measure ex vivo SARS-CoV-2-specific T cell responses (cellular immunity). This assay measures upregulated mRNA expression related to leukocyte activation 4 h after antigen stimulation. LeukoComplete™ system uses whole blood samples, eliminating the need for pretreatment before analysis. Furthermore, this system's high reproducibility is ensured through a series of operations from mRNA extraction to cDNA synthesis on a 96-well plate. In the performance evaluation using fresh blood from previously SARS-CoV-2-infected and COVID-19-vaccinated individuals, the EAGL assay had a comparable sensitivity and specificity to the ELISpot assay (EAGL: 1.000/1.000; ELISpot: 0.900/0.973). As a simple, high-throughput assay, the EAGL assay is also a quantitative test that is useful in studies with large sample numbers, such as monitoring new vaccine efficacies against novel coronaviruses or epidemiologic studies that require cellular immune testing during viral infection.