Adenovirus Antigens Research Articles

Which one is more dangerous in childhood Rotavirus or Adenovirus?

Objective: Determination of the frequency of Rotavirus and Adenovirus in patients diagnosed with gastroenteritis in the Pediatric Polyclinic of our hospital by immunochromatographic method and retrospective evaluation of the change in the distribution of the agent according to age, gender and vaccination status. Method: Those patients with complaints of diarrhea, vomiting, dehydration, and fever as well as those diagnosed with acute gastroenteritis were evaluated by taking fresh stool samples between January 2015 and November 2020. The data were presented using descriptive statistics. Results: The number of acute gastroenteritis patients included in the study was 1,192. The mean age of the patients was 18±SD months (min: 1 month, max: 180 months). Adenovirus and Rotavirus antigens were detected in 10% of all cases (n=119). Rotavirus antigen was positive in 6.6% (n=78) and Adenovirus antigen was positive in 3.1% (n=38) of all cases. The hospitalization rate was 5.1 times higher in Rotavirus positive cases (p

Comparison of two different serological methods in the diagnosis of Rotavirus and Adenovirus in stool samples

Objective: Rotaviruses are the most common cause of acute infectious diarrhea in children under 5 years of age worldwide. This study aims to compare the immunochromatographic and ELISA methods, determine the sensitivity and specificity of the methods used, and shed light on humanity to diagnose the disease correctly. Method: Stool samples of 1000 patients sent to Diyarbakır Pediatrics Hospital for rapid antigen testing of Rotavirus were studied. Single-stage Rotavirus and Adenovirus Co-immunochromatographic and ELISA methods were used in the examination of the samples. Samples with positive rapid test results were taken into 1.5 ml microcentrifuge tubes, and positive antigen samples collected for the ELISA test were stored at -80°C until the time to be studied. Results: Of 1000 stool samples analyzed, 40 (11.59%) of 345 girls and 60 (9.16%) of 655 boys had Rotavirus antigen in a total of 100 (10%) and 20 (2%) had Adenovirus antigen (P> 0.05). Viral antigen-positive cases were seen most frequently in winter months (December, January, February). There was no statistically significant difference between the data in terms of age and gender (P

Development of monoclonal antibodies targeting the conserved fragment of hexon protein to detect different serotypes of human adenovirus.

In this study, we selected the three most conserved antigenic fragments of human adenovirus to prepare a murine monoclonal antibody for the first time, and human adenovirus antigenic fragments with heretofore unheard of degrees of conservatism were isolated. The three monoclonal antibodies with the ability to recognize human respiratory adenovirus over a broad spectrum were screened by hybridoma and monoclonal antibody preparation. Human adenovirus infections are serious; however, therapeutic drugs and diagnostic reagents are scarce. Thus, to reduce the serious consequences of human viral infections and adenovirus pneumonitis, early diagnosis of infection is required. The present study provides three monoclonal antibodies capable of recognizing a wide range of human adenoviruses, thereby offering guidance for subsequent research and development.

Fecal leukocyte frequency in children with acute viral gastroenteritis: a single-center experience.

Our objective was to determine the frequency of rotavirus, adenovirus, and rota-adenovirus co-infections and investigate the fecal leukocyte rate associated with these infections in patients with gastroenteritis. This is a retrospective study. We identified patients who were admitted to the pediatric emergency department with acute gastroenteritis and had their stool samples tested for rotavirus and/or adenovirus antigens. Among them, we determined the individuals who underwent stool microscopy tests on the same day and recorded their results. A total of 1,577 patients who underwent testing for rotavirus and/or adenovirus antigens in their stool samples were identified. Among these patients, 583 individuals had concurrent fecal microscopy results. The prevalence of solely rotavirus antigen positivity was 16.4%, solely adenovirus antigen positivity was 2.9%, and rota-adenovirus co-infections were detected in 1.8% of the children. The fecal leukocyte rates in children infected with rotavirus, adenovirus, and rota-adenovirus co-infections were 4.8, 13.3, and 88.9%, respectively. The presence of fecal leukocytes was detected at a high rate in cases of viral gastroenteritis, especially in rota-adenovirus co-infections. Therefore, clinicians should not consider only bacterial pathogens in the presence of fecal leukocytes.

Evaluation of pediatric patients installed due to acute gastroenteritis

Objectives: Acute gastroenteritis is one of the most prevalent causes of death and morbidity in children and a significant health issue in Turkey, as well as developed and developing nations. The purpose of this study is to analyze retrospectively the patients with acute gastroenteritis who sought treatment at the Kızıltepe State Hospital in Mardin. Methods: This study was designed as a single-center retrospective study in which demographic variables were evaluated by taking fresh stool samples from the patients who applied to the Mardin Province Kızıltepe State Hospital between 01/11/2020 and 31/10/2021 with the complaint of diarrhea. The information of rotavirus, enteric adenovirus and amoeba viruses in stool samples was investigated by qualitative immunochromatographic test. The researcher assessed the research data utilizing the hospital's file archive materials and three factors set by the researcher. The researcher extracted the information about these factors from the patient files and stored it in a Microsoft Office Excel file. Results: According to the gender variable of the research participants, Amoeba positive rates were considerably higher in males than in girls (35.8% versus 22.6%, p = 0.046, respectively). According to the age groups variable, rotavirus antigen positive was statistically significantly greater in the 5-24 month age group compared to other age groups (p = 0.034). Similarly, Amoeba positive was statistically substantially higher in the 5-24 month age group compared to other age groups (p = 0.001). There was no significant variation between age groups in the distribution of adenovirus. According to the seasonal variable, rotavirus antigen positivity was most prevalent in the spring, and the difference between the spring and other seasons was statistically significant (p = 0.001), whereas amoeba positivity was most prevalent in the summer, with no statistically significant difference between the seasons (p = 0.003). The frequency of undiscovered variables was greater during the spring-summer months, and a statistically significant difference (p = 0.041) was identified between the groups. The seasonal variation in the prevalence of Adenovirus antigen positive was not statistically significant (p = 0.394). Conclusions: As a result, in poor and underdeveloped nations, it is among the top five causes of death in children under the age of five, in relation to acute gastroenteritis. Furthermore, the majority of these deaths may be minimized by preventative and prevention strategies. It is the responsibility of governments, health professionals, and families to foster a safe and healthy environment for all infants and children during their infancy and development. Community-based health strategies should be undertaken to lower the morbidity and death rates of millions of people worldwide who are exposed to harmful environmental conditions and malnutrition.

A highly sensitive and accurate dual-channel fluorescent immunochromatographic assay for simultaneous quantitative detection of influenza A virus and adenovirus antigens

Sensitivity and accuracy are the key performance metrics for evaluating immunochromatographic assay (ICA). In this study, we have developed a quantum dot nanobeads-based dual-channel fluorescent ICA (QBs-DICA) designed for the sensitive and accurate detection of both influenza A virus (IAV) and human adenovirus (ADV) antigens. Following systematic assay optimization, we achieved a remarkable improvement in sensitivity, with gains of up to two orders of magnitude at the best. To enhance signal accuracy for IAV and ADV testing, we implemented a temperature-controlled dual-channel detector during sample incubation and the chromatographic process, resulting in an approximate increase of 34.2% and 36.7%, respectively. The Limit of Detection (LOD) for IAV and ADV testing was robustly established at 165 copies/mL and 805 copies/mL, respectively. Furthermore, in the case of IAV-spiked and ADV-spiked samples, we achieved consistently high recoveries ranging from 94.5% to 104.8% and 94.7% to 106.4%, with impressively low coefficients of variation (CV) of below 7.16% and 6.25%, respectively. Our established QBs-DICA system has exhibited a remarkable enhancement in both sensitivity and accuracy, making it exceptionally well-suited for supporting the rapid advancement of clinical diagnosis and treatment strategies.

Study of Cosavirus, Salivirus, and Bufavirus viruses in children with acute gastroenteritis

BackgroundAcute gastroenteritis (AGE) in children represents a health problem. Besides common enteric viruses such as rotavirus and adenovirus, new viruses such as cosavirus, salivirus, and bufavirus may be associated with AGE. The objective of the study was to detect cosavirus, salivirus, and bufavirus viruses in children below 5 years with acute gastroenteritis by the use of real-time polymerase chain reaction (PCR) besides detection of rotavirus and adenovirus by enzyme-linked immunosorbent assay (ELISA).MethodThe study included 150 children ≤ 5 years with community-acquired diarrhea. Stool samples from children were subjected for the detection of rotavirus and adenovirus antigens by ELISA and for detection of buvavirus, salivirus, and cosavirus by real-time PCR.ResultsThe commonest virus detected in the stool samples of children with AGE was rotavirus 31.3% followed by adenovirus 24%. Among the new viruses studied, salivirus was detected in six samples (4.0%), buvavirus was detected in four samples (2.7%), and cosavirus was detected in two samples (1.3%). The mixed rotavirus detection with studied viruses was 23.4% for adenovirus, 4.3% for calicivirus, and 2.1% for bocavirus, and none of the detected cosavirus was associated with rotavirus. In the studied children, at least one of the new viruses was detected in ten children (6.7%). Buvavirus, salivirus, and cosavirus were detected as a single virus (0.7%) in the children with acute gastroenteritis and buvavirus was detected with cosavirus without other viruses in one sample (0.7%).ConclusionThe study reports the occurrence of buvavirus, cosavirus, and salivirus in the pediatric patients with community-acquired acute gastroenteritis. There was a high prevalence of rotavirus and adenovirus antigens in those patients with low positivity for buvavirus, cosavirus, and salivirus viruses. There is a need for a large cohort study to study the prevalence of buvavirus, cosavirus, and salivirus in pediatrics with acute gastroenteritis and to validate their association with the disease.

Prevalence of Rotavirus, Adenovirus, and Hepatitis A Virus in a Tertiary Care Hospital in Somalia

Rotavirus, one of the viral infectious agents that is transmitted mainly through the fecal-oral route and spreads easily in regions with poor sanitation conditions, is the most common causative agent of acute gastroenteritis in children under five years of age worldwide, and enteric adenoviruses are other frequently encountered causative agents of gastroenteritis in childhood. Hepatitis A virus (HAV) is also transmitted in similar routes and is endemic in regions with poor sanitation conditions and limited access to clean water and is usually acquired in early childhood in these regions. In this study conducted in Mogadishu Somalia, rotavirus and adenovirus antigen test (immunochromatographic rapid test) results in patients admitted to a tertiary hospital in the 9-month period between February 2019 and October 2019 and ELISA based HAV antibody test results studied in 2018-2019 were retrospectively examined and it was aimed to determine the distribution of positivity rates of these viruses by age, gender, and year. During the study period, 1136 patients (mean age 6.33±12.36) were tested for rotavirus and adenovirus antigens, and 362 patients (mean age 21.26±18.45) were tested for anti-HAV IgM/IgG antibodies. The positivity rates of rotavirus and adenovirus were found as 17.8% and 5.1%, respectively. The positivity rates of anti-HAV IgM and IgG antibodies were 26.5% and 85.4%. The age group with the highest rotavirus test positivity was babies under one year old (27.3%), positivity rate was also high in children aged 1-2 years old (20.9%), and this distribution was similar for adenovirus. Although a small number of patients were tested in under five years of age, anti-HAV IgG seropositivity was 60% and above in all age groups. The highest anti-HAV IgM positivity rates were observed in children 2-<5 and 5-15 years of age, 52.9% and 44% respectively. Rotavirus antigen positivity was found at high levels in the three-month period covering June, July, and August 2019. In July (2019), it was observed that the number of rotavirus and adenovirus antigen test requests were increased, and also, at the same time the highest positivity rates for both viruses were observed; 31.2% and 9.5% for rotavirus and adenovirus. Rotavirus and enteric adenovirus co-infection was detected in 2.4% (27/1136) of the patients, and 23 (85.2%) of these were under five years of age children. Our study results show that children under the age of two are especially affected by rotavirus and adenovirus infections in Somalia and indicate that HAV infections are acquired at an early childhood. We can say that it may be useful to review vaccination programs as an important public health measure to reduce the burden of mortality and morbidity associated with HAV and rotavirus, which have a high prevalence and also have protective vaccines.

Frequency of Rotavirus and Adenovirus in Children with Diarrhea

ABSTRACT Aim: The aim of this study is retrospective evaluation of the frequency of rotavirus and adenovirus in stool, and their distribution according to gender, age and seasons in children with diarrhea admitted at outpatients or hospitalized in our hospital. Material and Methods: Stool samples of patients aged between 0-18 years received at the Medical Microbiology Laboratory between 2021–2022 were evaluated for rotavirus–adenovirus. Rotavirus and adenovirus antigens were determined qualitatively by immunochromatographic cassette test method. Chi-square test was used in the statistical analysis. Results: A total of 1148 stool samples of pediatric patients were received by our laboratory during these two years for rotavirus and adenovirus antigen test. Of 1148 patients, 8.6% were positive for rotavirus, 5.1% for adenovirus, and 0.6% for both rotavirus and adenovirus antigens. Rotavirus and adenovirus was positive in 7.2% and 5.6% of males, respectively, and 10.6% and 4.5% of females, and there were no statistically significant differences. Rotavirus was most frequently found in the age group 3-5 years (11.6%) and adenovirus was most frequently found in the age group 6-9 years (8.4%), with no significant difference. Rotavirus was most frequently detected in spring (12.9%) while adenovirus was found most frequently in winter (8.1%), without significant differences. Antigen positivity was 4.1% and 4.9% in outpatients for rotavirus and adenovirus, respectively, and 15.1% and 5.5% in hospitalized patients. Rotavirus positivity was significantly higher in hospitalized patients than outpatients, and adenovirus positivity did not show a significant difference. Conclusion: We found that rotavirus and adenovirus were significant agents causing diarrhea in children, especially those younger than 5 years old, and that its frequency increased in winter and spring, and as rotavirus is a cause of hospitalization, implementation of rotavirus vaccine into routine vaccination programs seem to be beneficial for patients.

Adenovirus-assembled DC vaccine induces dual-targeting CTLs for tumor antigen and adenovirus to eradicate tumors

The dendritic cell (DC) vaccine is a promising cancerimmunotherapy strategy, but its efficacy in treating the solid tumor is limited. To overcome this limitation, an oncolytic adenovirus (OAV-IL-12) was developed to enhance antigen targeting ability of adenovirus-assembled DC vaccine (DCs-CD137L/CAIX) for renal carcinoma treatment. Peritumoral administration of OAV-IL-12 increased the number of tumor-infiltrating DCs and their subsets (CD8+DCs and CD103+DCs). Combining OAV-IL-12 with DCs-CD137L/CAIX significantly inhibited the growth of subcutaneous tumors by inducing potent cytotoxic T lymphocyte (CTL) effect and improving the immune infiltration in tumor lesions. Interestingly, this treatment also reduced tumor growth distal to the OAV-IL-12 injecting side via eliciting a systemic CTL response. Furthermore, OAV-IL-12 potentiated DCs-CD137L/CAIX treatment induced dual CTL responses against both CAIX and adenovirus antigens. The therapeutic benefits of this treatment approach mainly relied on multifunctional CD8+T cell immune responses, as indicated by the depletion assay. Moreover, OAV-IL-12 potentiated DCs-CD137L/CAIX treatment generated a long-lasting protective effect against tumors by inducing memory CD8+T cell immune responses. These results suggest that the effective tumor targeting of the adenovirus-based DC vaccine, boosted by OAV-IL-12, is a promising treatment approach for renal carcinoma and other solid tumors.

Fecal rotavirus and adenovirus antigen detection and clinical analysis of children with acute gastroenteritis in a hospital of Beijing City from 2019 to 2022

As a single-center retrospective study, we analyzed the results of rotavirus and human adenovirus antigens in stool samples with colloidal gold immunochromatography method in children with acute gastroenteritis under the age of five who were treated in our hospital from 2019 to 2022. After excluding nonconforming cases and duplicate cases, 2 896 cases were included, of which 559 cases were detected with at least one viral antigen. According to the test results, they were divided into RV positive group, HAdV positive group and RV & HAdV double positive group. The gender, age, seasonal distribution, clinical symptoms and related laboratory tests were compared and analyzed with χ2 test, analysis of variance and nonparametric test. Among the single samples from 2 896 children, the positive rate of RV antigen was 6.21% (180/2 896), the positive rate of HAdV antigen was 10.91% (316/2 896), and the double positive rate of RV & HAdV was 2.18% (63/2 896). The positive rate of HAdV antigen in 2021 was 16.11%, a significant increase compared with 6.20% in 2020. RV infection has obvious seasonality, and spring and winter are the seasons with high incidence of infection (χ2=74.018, P<0.001), while HAdV infection has no obvious seasonality (χ2=2.110, P=0.550), showing sporadic infection throughout the year. The proportions of fever and vomiting symptoms in children with RV infection were significantly higher than those in the HAdV infection group (χ2=40.401, P<0.001; χ2=32.593, P<0.001), but the positive rate of white blood cells in the stool was significantly lower than that in the HAdV infection group (χ2=13.741,P<0.01). In summary, paying attention to the epidemiological changes of RV and HAdV is of great significance for clinical diagnosis and treatment and disease prevention and control.

Detection of Rotavirus and Enteric Adenovirus among children with Acute Gastroenteritis admitted to Benghazi Pediatric Hospital

Rotavirus A and enteric adenovirus are common causes of acute gastroenteritis (AGE), especially in children under five years of age worldwide. This study aimed to detect the incidence of rotavirus and enteric adenovirus antigens in stool specimens of children with AGE admitted to a Benghazi pediatric hospital between February and April 2019. The presence of rotavirus and adenovirus antigens in the samples was tested using an immunochromatographic method (ICT). Between the 273 stool samples, 119 (43.58%) were positive for viruses causing AGE. Rotavirus 74 (27.1%) was the most frequently detected, followed by adenovirus 45 (16.5%). However, 22 (8.1%) of the samples were detected to be positive for both virus antigens (co-infection)

Frequency and seasonal distribution of adenovirus and rotavirus in children diagnosed with acute gastroenteritis: A single centre experience

Aim: We aimed to investigate the relationship between age, gender, and season with respect to the frequency of rotavirus and adenovirus antigens in stool specimens obtained from children one month to 18 years of age who were diagnosed with acute gastroenteritis.&#x0D; Materials and Methods: The records of stool specimen analyses for 1960 patients with diagnosis of acute gastroenteritis at our hospital from January 2017 to August 2022 were retrospectively examined. The patient's admission year, season, gender, age, and stool viral antigen test results were retrospectively analyzed from the file records.&#x0D; Results: Viral antigen was detected in stool specimen in 364 (13.8%) of the patients included in the study, while 92 (4.7%) of them were rotavirus and 180 (9.1%) were adenoviruses. We found that both rotavirus and adenovirus were most common in the children one month-2 years of age. In our study, rotavirus was most commonly detected in December and winter, while adenovirus was detected in March and spring. Twenty-six (28.2%) patients with rotavirus gastroenteritis and 68 (37.7%) patients with adenovirus gastroenteritis were hospitalized and treated.&#x0D; Conclusion: Our study showed now that rotavirus and adenovirus, which are the agents of viral gastroenteritis, are seen at a substantial rate. Especially in children under the two years of age, the frequency of detection of viral agents is higher. Enteric adenovirus and rotavirus were detected more frequently in winter and spring. We suggest that viral gastroenteritis agents should be considered and examined in children with suspected gastroenteritis.

Pathological and Immunohistochemical Examinations in Chukar Partridge (Alectoris chukar) of Wild and Captive Populations

The aim of this study was to evaluate the health situation of chukar partridges through several diagnostic methods. We investigated a total of 224 birds in eighteen populations throughout Turkey, fourteen wild and four captive. The molecular sexing method was used for gender identification. Clinically, traumatic lesions and inflammatory reactions were the most commonly observed in the eyes and extremities of the Chukar Partridges in the breeding stations. At necropsy, the most common findings were enteritis and liver lesions. At the histopathological examination, pneumonia, anthracosis, and inflammatory changes in the digestive system were among the common findings. Interestingly, liver parasites were found in wild samples. At the immunohistochemical examinations, the tissues were evaluated for Marek’s disease (MD), Adenovirus, Avian mycobacteriosis (AMB), and Aspergillosis. While MD and AMB were not found in breeding stations, we determined them from wild populations. Aspergillus was found in both wild and captive populations; Adenovirus antigens were found only in breeding stations. When the captive and wild populations were evaluated together, MD 1.3%, AMB 0.9%, Aspergillosis 1.3%, Adenovirus 1.8% were found. The relation between sex and diseases was also examined. As a result, the data of this study showed that chukar partridges from both breeding stations and wild populations are not an important source of diseases, but especially released partridges from breeding stations may carry some microorganisms. For that reason, captive populations should be regularly monitored for contagious diseases.

Comparative Analysis of Enzyme-Linked Immunosorbent Assay and Immunochromatography for Rotavirus and Adenovirus Detection in Children below Five Years with Acute Gastroenteritis.

Introduction The most frequent etiologies of viral gastroenteritis among young children are rotavirus and enteric adenovirus. The clinical signs and symptoms of viral gastroenteritis are not distinct enough to allow for diagnosis. For the diagnosis and treatment of acute gastroenteritis, it is preferable to use quick, simple, and low-cost procedures. This study was undertaken to determine efficacy of immune-chromatography test (ICT) in comparison with enzyme-linked immunosorbent assay (ELISA) to detect rotavirus and adenovirus antigen in fecal specimen among children less than 5 years of age with acute gastroenteritis. Materials and Methods In a cross-sectional observational study, 314 fecal samples were collected from children aged less than 5 years with acute gastroenteritis attending or admitted to a tertiary care hospital during the 1 year study period. Samples were tested for rotavirus and adenovirus antigen using ICT and ELISA. Results Among the 314 children evaluated, 112 (35.66%) had rotavirus infection, nine (2.86%) had adenovirus infection, and three (0.95%) had both rotavirus and adenovirus infection. This study found that ICT is 98.20% sensitive and 100% specific for the diagnosis of rotaviral diarrhea and 100% sensitive and 99.7% specific for adenovirus diarrhea, compared to ELISA. Conclusion Immunochromatography tests used for the detection of rotavirus and adenovirus in the fecal sample showed a high degree of sensitivity and specificity. The ICT is easy to perform and rapid, and it does not require any special equipment. Hence, the ICT could be used as an alternative method for detecting viral pathogens in clinical practice.

Molecular Study of Adenovirus Genotypes 40 and 41 in Children with Acute Gastroenteritis.

Adenovirus is a common virus associated with acute gastroenteritis in children. There are certain genotypes that are prevalent in these infections, such as genotypes 40 and 41. The aim of the present study was to investigate the incidence of adenovirus genotypes 40 and 41 in children with acute gastroenteritis by polymerase chain reaction (PCR) and also to determine the possibility of Adenovirus co-infections with Rotavirus. The study was a cross-sectional study that included 100 children with acute gastroenteritis. The children were subjected to full history taking and clinical examination. Stool samples from the patients were subjected to detection of adenovirus and rotavirus antigens by enzyme-linked immunosorbent assay (ELISA) and detection of adenovirus genotypes 40 and 41 by polymerase chain reaction (PCR). The most prevalent virus by the used methods was rotavirus antigen in the stool (35%). Adenovirus antigen detection was positive in 23% of the stool samples, with positive PCR for these samples in 22%. The ADv40 was detected in 13 samples, and ADv41 was detected in 9 samples. One positive sample by adenovirus antigen ELISA was negative by PCR for these genotypes. Mixed rotavirus and adenovirus by ELISA were detected in 7% of the children. In patients with positive adenovirus antigen by ELISA, the most common symptoms were vomiting (54.5%) and abdominal pain (45.5%). An insignificant difference between fever (P=0.94) and abdominal pain (P=0.63) was detected in children infected with adenovirus compared to patients infected with other organisms. The adenovirus was detected in 68.2% of children with acute gastroenteritis ≤ 24 months. Vomiting was significantly increased in children with adenovirus (54.5%) compared to children negative for adenovirus (23.1%-P=0.004, OR 4.0, 95%CI: 1.5-10.8). The study highlights the presence of adenovirus genotypes 40 and 41 in the stool of children with acute gastroenteritis. Combined rotavirus and adenovirus infections were detected in our study.

IMMU-39. NANOPARTICLE TREATMENT REBALANCES IMMUNODOMINANCE OF ANTI-VIRUS IMMUNITY TO ENHANCE ANTI-TUMOR IMMUNITY DURING ONCOLYTIC ADENOVIRUS THERAPY IN SOLID TUMORS

Abstract Oncolytic virotherapy shows great potential for treating brain tumors and other solid tumors that metastasize to the brain. A phase I clinical trial testing the oncolytic adenovirus Delta-24-RGD (DNX-2401) in patients with recurrent malignant gliomas demonstrated significant clinical benefits for a subset of patients, and another phase I trial testing Delta-24-RGD in patients with pediatric brain tumors also indicated similar clinical benefits. However, virus injection in tumors initiates both anti-virus and anti-tumor immune responses by activating respective clones of CD8+ T-cells, which compete for limited resources for clonal expansion. Expansion of T-cells against highly immunogenic viral antigens might limit the expansion of subdominant clones against tumor antigens. We hypothesized that inducing immune tolerance for the dominant viral antigens will allow the expansion of previously subdominant tumor-specific T-cells. In this work, we observed that nanoparticles encapsulating adenoviral antigens successfully induced immune tolerance for viral antigens. These nanoparticles were taken up by liver resident macrophages, which are involved in maintaining peripheral immune tolerance. RNA-sequencing revealed that T-cells recognizing the encapsulated antigens had unique transcriptome signatures with upregulation of genes specifically involved in peripheral immune tolerance, including immune coinhibitory molecules. Virus-specific immune tolerance using nanoparticles redirected the focus of the immune response towards antigens for melanoma as measured by interferon-gamma secretion (P &amp;lt; 0.0001). Reduction of virus-specific T-cells and simultaneous expansion of tumor-specific T-cell clones were confirmed with tetramer staining (P &amp;lt; 0.05). Importantly, virotherapy in combination with nanoparticle-induced immune tolerance towards viral antigens increased the percentage of long-term survivors compared to virus treatment alone (100% versus 50%). Our data provide the basis to develop future clinical trials that aim to maximize the potential of cancer virotherapy in solid tumors.

Epidemiology of Human Adenovirus in Pakistani Children Hospitalized with Community-Acquired Gastroenteritis under the Age of Five Years.

Acute gastroenteritis is the major cause of morbidity and mortality among infants and children around the globe. Along with other enteropathogens, human adenovirus (HadV) is a major etiological agent associated with diarrhea in young children. However, information about the epidemiology of Adenoviruses in Pakistan is limited or has not been reported. A total of 1082 stool samples were collected from patients with acute gastroenteritis under the age of five years with symptoms of diarrhea, vomiting, nausea, and abdominal cramps who visited Benazir Bhutto Hospital Rawalpindi and Children’s hospital in Lahore of Punjab Province in Pakistan. Of this, 384 cases with no blood in their stool, negative for Rotavirus, and under the age of five years were recruited in this study. Human Adenoviruses were isolated in the human epithelial HEp-2 cell line. Furthermore, adenovirus antigen detection was carried out by an enzyme-linked immunosorbent assay (ELISA), and then all positive and negative samples were confirmed by nested PCR. After inoculating a clear stool supernatant on HEp-2 cell lines, we observed a positive cytopathic effect in 65 (16%) cases. Using an enzyme-linked immunosorbent assay, HAdV antigens were detected in 54 (14.06%) of the clear supernatant from gastroenteritis cases. However, HAdV hexon coding regions were amplified in 57 (14.80%) fecal samples, mainly from patients ≤24 months of age. The findings of this study suggest that adenovirus circulates significantly in the children population under the age of five years and may be the potential etiological factor of acute gastroenteritis in the mentioned cities. This study provides baseline data about the possible role of adenovirus in causing viral diarrhea in children. Further large-scale epidemiological surveys are recommended to better understand disease burden, etiological agents, and its clinical impact across the country.

Akut Viral Gastroenteritli Çocuklarda COVID-19 Pandemisi Öncesi ve Sırasında Rotavirüs ve Enterik Adenovirüs Sıklığının Araştırılması

Aim: Rotavirus and enteric adenovirus are common causes of acute gastroenteritis in children worldwide. With the emergence of COVID-19 pandemic, measures for pandemic management have also affected frequency of other viral agents. The aim of this study was to investigate changing antigen positivity pattern of rotavirus and enteric adenovirus before and during pandemic and to determine its distribution according to age groups, gender and season of admittance. &#x0D; Material and Method: Test results of 14670 stool samples of pediatric patients with gastroenteritis between January 2019-June 2021 were evaluated retrospectively. Rotavirus and enteric adenovirus antigens were detected by immunochromatography.&#x0D; Results: The positivity rates of rotavirus and enteric adenovirus antigen were 9.5% and 1.6%, respectively, before pandemic. A statistically significant decrease was detected for positivity rates of both these viruses during pandemic. Rotavirus antigen positivity significantly increased in 0-2 age group during pandemic (72.9%) compared to pre-pandemic period (70.4%) and significantly decreased from 4.1% to 3.5% in age group of 8-14 during pandemic. Distribution of adenovirus antigen positivity according to age groups did not differ significantly. There was no significant association between period and gender in terms of positivity rates. In pre-pandemic winter, rotavirus and adenovirus positivity rates were found to be significantly higher than in other seasons whereas during pandemic, positivity rates significantly increased in spring and summer.&#x0D; Conclusion: Frequencies of rotavirus and enteric adenovirus have shown a significant decrease during pandemic. Infection control measures have play an important role in reducing incidence of enteric viruses as well as SARS-CoV-2.

Engineering T cells to suppress acute GVHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation

AbstractAcute graft-versus-host disease (aGVHD) limits the therapeutic benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and requires immunosuppressive prophylaxis that compromises antitumor and antipathogen immunity. OX40 is a costimulatory receptor upregulated on circulating T cells in aGVHD and plays a central role in driving the expansion of alloreactive T cells. Here, we show that OX40 is also upregulated on T cells infiltrating GVHD target organs in a rhesus macaque model, supporting the hypothesis that targeted ablation of OX40+ T cells will mitigate GVHD pathogenesis. We thus created an OX40-specific cytotoxic receptor that, when expressed on human T cells, enables selective elimination of OX40+ T cells. Because OX40 is primarily upregulated on CD4+ T cells upon activation, engineered OX40-specific T cells mediated potent cytotoxicity against activated CD4+ T cells and suppressed alloreactive T-cell expansion in a mixed lymphocyte reaction model. OX40 targeting did not inhibit antiviral activity of memory T cells specific to Epstein-Barr virus, cytomegalovirus, and adenoviral antigens. Systemic administration of OX40-targeting T cells fully protected mice from fatal xenogeneic GVHD mediated by human peripheral blood mononuclear cells. Furthermore, combining OX40 targeting with a leukemia-specific chimeric antigen receptor in a single T cell product provides simultaneous protection against leukemia and aGVHD in a mouse xenograft model of residual disease posttransplant. These results underscore the central role of OX40+ T cells in mediating aGVHD pathogenesis and support the feasibility of a bifunctional engineered T-cell product derived from the stem cell donor to suppress both disease relapse and aGVHD following allo-HSCT.