Immunosuppressive Disease Research Articles

First detection and genetic characterization of chicken infectious anemia virus in the Mekong Delta, Vietnam.

Chicken infectious anemia (CIA) caused by the CIA virus (CIAV) is considered one of the most important immunosuppressive diseases affecting chickens and recently poses a great economic burden to the poultry industry worldwide. This study aims to identify the presence of CIAV in the Mekong Delta (MD), Vietnam, and to determine genotypes of CIAVs that are currently circulating in this area. Organ samples (spleen, liver, and thymus) of 144 chickens suspected with CIA from 47 poultry farms were collected. A total of 47 pooled samples, each containing 2-4 chickens from each farm, were tested for the presence of CIAV. Twenty out of 47 pooled organ samples (pool of 2-4 chickens per farm) were positive for CIAV using polymerase chain reaction targeting the viral VP1 gene. The VP1 amplicons of eight representative CIAVs were subjected to sequencing and genetic characterization. Phylogenetic analysis based on partial VP1 gene sequence revealed that the CIAVs detected in the MD grouped into different genotypes of II, IIIa, and IIIc together with CIAVs previously detected in the northern Vietnam and other Asian countries. The phylogenetic analysis also confirmed that detected CIAVs genetically differed from vaccine strains. In addition, deduced amino acids of the VP1 identified several critical amino acid substitutions in the VP1 protein that are likely associated with the virulence of CIAV. This is the first report to detect and determine the genetic characterization of the circulating CIAVs in the MD. Therefore, this study provides an important understanding of the evolution of CIAVs and highlights the importance of implementing prompt control measures against CIAVs in the MD and Vietnam.

Proposal for a Severity Score (DeASI, Dermatophytosis Area and Severity Index) for the Evaluation of Dermatophyte Infections - A Delphi Consensus Study.

There has been a significant increase in the incidence of recurrent, resistant, and extensive dermatophyte infections worldwide recently. This menace has spurred the need for more well-designed randomized controlled trials to optimize the treatment of dermatophyte skin infections. One of the limitations in designing such studies is the limited availability of standard and validated score, to measure the severity of dermatophyte infections. To create a severity score for the evaluation of dermatophyte infections. A Delphi consensus model was used to frame a severity scoring tool for superficial dermatophyte skin infections. Fourteen experts participated in the first round and twelve experts participated in the second round. Based on the expert consensus, a final scoring system proposed was: Final Severity Score (FSS) = Sum total of Body Surface Area (BSA) in hand units for each patch multiplied by the sum of the scores for pruritis (P), lichenification (L), and actively raised borders (A) for each patch (FSS = BSA in hand units × (P + E + L + A) of patch 1 + BSA in hand units × (P + E + A) of patch 2 …etc.). For measuring hand units more accurately fractional values of 0.25 can be used (0.25 corresponding to an approximate 1/4th of a hand unit). A score of +1 will be added in case of the following - 1) Close contact/family member affected, 2) History of at least one recurrence in the previous 6 months after a course of oral antifungals, 3) History of immunosuppression (on immunosuppressive medication or having underlying immunosuppressive disease). The scores will be valid only if the patient has not used any treatment topical or systemic, for at least 2 weeks before enrolment. The proposed Dermatophytosis Area and Severity Index (DeASI) score will help the physicians and researchers standardize the treatment protocol for dermatophytosis, henceforth, assessing the response to therapy. This will also help to standardize the parameters of effectiveness while designing any clinical trial.

Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic

ObjectiveTo assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. MethodsA cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). ResultsThe frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00‒7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08‒3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12‒4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93‒0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95‒0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16‒0.77; p = 0.026) remained inversely associated with abnormal HI scores. ConclusionThe present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.

Studies on immunostimulatory effect of efcovida powder on Cyclophosphamide-induced immunosuppression in mice

To evaluate the immunostimulatory activity of Efcovida powder, we induced immunosuppression in Swiss mice by cyclophosphamide (CP). Efcovida powder at two doses of 60 mg/kg b.w and 120 mg/kg b.w were administered orally for seven consecutive days to animals. CP (200 mg/kg i.p.) was injected on the 4th day. The result showed that Efcovida powder at the dose of 60 mg/kg b.w only posed an immunostimulating potency in the cyclophosphamide-induced immunosuppression model while Efcovida powder at the dose of 120 mg/kg b.w significantly ameliorated the effects of CP on delayed-type hypersensitivity (DTH) response, leukocyte quantity, relative thymus weight, serum IL-4, IL-6 concentration, and micro-histological images of spleen and thymus. This suggested the potential of Efcovida powder to treat immunosuppression diseases in clinical practice.

Analysis of network pharmacology and experimental verification to explore the mechanism of Modified Guilu Erxian Glue in the treatment of low immune function

ObjectiveThe aim of this study was to investigate the therapeutic effect of modified Guilu Erxian Gum (MGEG) on cyclophosphamide (Cy) induced immunosuppression in mice. Based on network pharmacology, the comprehensive mechanism of immune hypofunction was preliminarily discussed. MethodsCyimmunosuppression model was established to observe the effect of MGEG compound on immune injury in mice. The best compound was screened for network pharmacological analysis, and the "drug component" and "disease drug target" networks were established by network pharmacological methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted according to the common target between Chinese herbal medicine and low immunity to determine the biological process and signal pathway. The core components and targets obtained by network pharmacology were verified by Western blot analysis (WB). ResultsIn vivo experiments showed that the weight, thymus index, organ index, carbon particle clearance index, phagocytosis index, foot thickening level, macrophage phagocytosis and natural killer cell killing activity of immunosuppressed mice induced by Cy were significantly increased by Codonopsis pilosula, Guilu Erxian Jiaowei Wuxing Powder (CGW) (p<0.05 or p<0.01). In addition, CGW significantly increased the humoral and cellular immunity of immunosuppressed mice (p<0.05 or p<0.01). Based on the network pharmacological analysis, it is predicted that CGW contains 125 potential bioactive components, involving 489 action targets, and 125 common targets that may be related to immunosuppressive diseases. Based on the establishment of protein protein interaction network, five central nodes were identified as active factors involved in major biological functions. David, ClueGO and Metascape enrichment analysis all proved that CGW plays an important role in the regulation of immune function. By KEGG analysis, TNF signaling pathway is considered to be one of the main signaling pathways of CGW in the treatment of immunosuppression, including a wide range of intracellular signaling pathways. NF-κB signaling pathway regulates inflammation and immunity in TNF signaling pathway. WB showed that CGW significantly promoted NF-κB The expression of signal pathway further confirms that Chinese herbal compound can enhance the body's immunity and NF-κB signal path activation. ConclusionBased on network pharmacology and experimental verification, the potential targets and pathways of CGW to improve Cy induced immunosuppression and its potential therapeutic mechanism were revealed, providing a theoretical basis for development of traditional Chinese medicine. Guilu Erxian Gum (龟鹿二仙胶, GEG) is a traditional Chinese medicine prescription, which is widely used to treat low immunity and immune function impairment caused by chemotherapy. However, its potential pharmacological mechanism remains largely unknown.

Immunotoxicity In Vitro Assays for Environmental Pollutants under Paradigm Shift in Toxicity Tests.

With the outbreak of COVID-19, increasingly more attention has been paid to the effects of environmental factors on the immune system of organisms, because environmental pollutants may act in synergy with viruses by affecting the immunity of organisms. The immune system is a developing defense system formed by all metazoans in the course of struggling with various internal and external factors, whose damage may lead to increased susceptibility to pathogens and diseases. Due to a greater vulnerability of the immune system, immunotoxicity has the potential to be the early event of other toxic effects, and should be incorporated into environmental risk assessment. However, compared with other toxicity endpoints, e.g., genotoxicity, endocrine toxicity, or developmental toxicity, there are many challenges for the immunotoxicity test of environmental pollutants; this is due to the lack of detailed mechanisms of action and reliable assay methods. In addition, with the strong appeal for animal-free experiments, there has been a significant shift in the toxicity test paradigm, from traditional animal experiments to high-throughput in vitro assays that rely on cell lines. Therefore, there is an urgent need to build high-though put immunotoxicity test methods to screen massive environmental pollutants. This paper reviews the common methods of immunotoxicity assays, including assays for direct immunotoxicity and skin sensitization. Direct immunotoxicity mainly refers to immunosuppression, for which the assays mostly use mixed immune cells or isolated single cells from animals with obvious problems, such as high cost, complex experimental operation, strong variability and so on. Meanwhile, there have been no stable and standard cell lines targeting immune functions developed for high-throughput tests. Compared with direct immunotoxicity, skin sensitizer screening has developed relatively mature in vitro assay methods based on an adverse outcome pathway (AOP), which points out the way forward for the paradigm shift in toxicity tests. According to the experience of skin sensitizer screening, this paper proposes that we also should seek appropriate nodes and establish more complete AOPs for immunosuppression and other immune-mediated diseases. Then, effective in vitro immunotoxicity assay methods can be developed targeting key events, simultaneously coordinating the studies of the chemical immunotoxicity mechanism, and further promoting the paradigm shift in the immunotoxicity test.

Pfizer-BioNTech and Sinopharm: A comparative study on biochemical and immunological responses in healthy individuals post-vaccination against COVID-19

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. Since 2019, it has spread all over the globe, causing a pandemic that is still ongoing. COVID-19 vaccines protect against this disease through different strategies. Pfizer-BioNTech and Sinopharm vaccines were the most used vaccines in Iraq. Both vaccines have a specific mechanism to trigger the immune system in cells. This research aims to compare the biochemical and immunological responses in vaccinated individuals with either the Pfizer-BioNTech COVID-19 vaccine or the Sinopharm vaccine. This cohort study included 120 Iraqi adults vaccinated with two doses, 21 days apart, using either the Pfizer or the Sinopharm vaccine. Forty subjects received the Pfizer vaccine, 40 subjects received the Sinopharm vaccine, and the other 40 subjects were unvaccinated. After 6 weeks, the second dose was administered, and the blood samples were collected. Our findings revealed that the biochemical biomarkers, urea, creatinine, aspartate aminotransferase, and alkaline phosphatase, seem to be not affected by the vaccines used. However, both vaccines significantly reduced alanine aminotransferase levels (p &lt; 0.05). In contrast, the immunological biomarkers such as IgG, IgM, C3, IL-2, and hs-CRP remarkably responded to both vaccines (p &lt; 0.01), while procalcitonin levels were significantly increased by the Pfizer vaccine (p &lt; 0.05). The study concluded that the Pfizer-BioNTech vaccine boosted the immune system more than the Sinopharm vaccine. A booster dose is advised for people who have already taken Sinopharm or have long-term immunosuppressive diseases.

1159. Treatment experience of regdanvimab for mild to moderate COVID-19 hospitalized patients in the Delta variant-predominant period in Korea

Abstract Background Regdanvimab is the only monoclonal antibody available in Korea that targets the receptor-binding domain of SARS-CoV-2. Although the efficacy of regdanvimab against the original and beta variant viruses was demonstrated, it remains uncertain whether it has therapeutic effect on delta variant in the real world. Methods We retrospectively evaluated the characteristics and clinical outcome of patients hospitalized for COVID-19 and treated with regdanvimab in two university-affiliated hospitals between September and December 2021, during the delta variant-predominant period in Korea. Results A total of 374 mild to moderate COVID-19 patients treated with regdanvimab were included in this study. The median age was 65 (interquartile range, IQR 17-92) and 178 (47.6%) patients were male. A total of 322 (86.1%) patients had median 2 (IQR 1-3) risk factors for disease progression. The most common underlying disease was cardiovascular disease (198, 52.9%), followed by diabetes mellitus (95, 25.4%), cancer (40, 10.7%), chronic lung disease (34, 9.1%), immunosuppression (1 7, 4.5%), and chronic kidney disease (12, 3.2%). There were 43 (11.5%) patients with a body mass index ≥ 30. The median time to regdanvimab treatment from symptom onset was 4 (IQR 2-6) days. 226 (60.4%) patients were fully vaccinated, and 109 (29.1%) were not vaccinated at all. 185 (49.5%) patients had pneumonia. Most (342/374, 91.4%) patients improved without any other treatment for COVID-19 and were discharged. Only 32 (8.6%) patients required other therapeutic agents such as remdesivir, corticosteroids or oxygen therapy after regdanvimab administration. The time from regdanvimab infusion to addition of other therapeutic agents was median 5 days (IQR 3-6.5). When comparing the characteristics of 32 patients who needed other treatment with those who improved only with regdanvimab treatment, there was a significant difference in the presence of pneumonia (27/32, 84.4% vs. 158/342, 46.2%, P&amp;lt; 0.001) and there was no significant difference in vaccination status (15/32, 46.9% vs. 211/342 61.7% P=0.101). Conclusion This study shows the potential clinical benefits of regdanvimab in mild to moderate COVID-19 patients in the real world during the delta variant predominant period in Korea. Disclosures All Authors: No reported disclosures.

Acinetobacter Lwofii, an unusual cause of infectious pericarditis complicated with cardiac tamponade: a case report

Bacterial pericarditis can be considered a rare pathology, usually associated with cardiac procedures and, to a lesser extent, with immunosuppression and chronic diseases. The importance of its knowledge lies in the fact that mortality can reach up to 100% in untreated patients. Once diagnosed, pericardiocentesis and administration of intravenous antimicrobial therapy are mandatory for the prevention of its complications, which include cardiac tamponade and sepsis. Here we present an exceptional case of infectious pericarditis due to Acinetobacter Lwoffii in an older adult, which was complicated by pericardial effusion and cardiac tamponade.

Research Note: Effect of Rubia cordifolia L. processed Terminalia chebula Retz polysaccharide on the histological structure and apoptosis in the spleen in immunosuppressed Chinese yellow quail

It is generally accepted herbal polysaccharide and is a bioactive compound of herbal medicines with immunomodulatory activities. It has a wide range of pharmacological effects. It can be used as a green substitute for antibiotics or as a feed additive in quail breeding. Therefore, the herbal polysaccharide has a broader and safer application prospect. The immunosuppressive disease of quail is one of the most important infectious diseases. It seriously affects the growth, development, and production performance of quail, causing huge economic losses to quail industry. However, there is no report on the effective alleviation of spleen injury in immunosuppressed animals by herbal polysaccharide. Therefore, we established a pathological model of immunosuppressive Chinese yellow quail for the first time, with the Terminalia chebula Retz polysaccharide (TCP) as the control, and histological observation, TUNEL staining were used to study the effects of Rubia cordifolia L. processed Terminalia chebula Retz polysaccharide (RTCP) on splenic tissue structure and apoptosis of immunosuppressed Chinese yellow quail. The experimental results showed that spleen organ index of the cyclophosphamide (CTX) group was significantly lower than these of blank control group, the TCP group and the RTCP group (P < 0.05). And the number of splenic nodules in the CTX group was significantly lower than that in the blank control group (P < 0.01). Compared with the CTX group, the spleen volume of the TCP group and the RTCP group increased, and the number and area of spleen nodules increased. Among them, the spleen nodules in the RTCP group were significantly more higher than that in the CTX group (P < 0.01). Meanwhile, TUNEL staining showed that the TUNEL positive cells in the CTX group were the most significantly higher than those in the blank control group (P < 0.01). TCP group and RTCP group were significantly higher than the blank control group (P < 0.01), but significantly lower than CTX group (P < 0.05). All these results suggested that RTCP could effectively improve CTX-induced spleen damage in immunosuppressed Chinese yellow quails by promoting the recovery of spleen organ index, repairing the spleen tissue structure, and diminishing the apoptosis. Moreover, RTCP is more effective than TCP. The results prove that the efficacy of RTCP in protecting spleen from CTX induced injury was enhanced after processing with Rubia cordifolia L. Therefore, our findings will provide more possibilities to promote the clinical application and development of processed traditional Chinese medicine in the further.

Interaction between chicken TRIM25 and MDA5 and their role in mediated antiviral activity against IBDV infection.

Infectious Bursal Disease Virus (IBDV) is the causative agent of an immunosuppressive disease that affects domestic chickens (Gallus gallus) severely affecting poultry industry worldwide. IBDV infection is characterized by a rapid depletion of the bursal B cell population by apoptosis and the atrophy of this chief lymphoid organ. Previous results from our laboratory have shown that exposure of infected cells to type I IFN leads to an exacerbated apoptosis, indicating an important role of IFN in IBDV pathogenesis. It has been described that recognition of the dsRNA IBDV genome by MDA5, the only known cytoplasmic pattern recognition receptor for viral RNA in chickens, leads to type I IFN production. Here, we confirm that TRIM25, an E3 ubiquitin ligase that leads to RIG-I activation in mammalian cells, significantly contributes to positively regulate MDA5-mediated activation of the IFN-inducing pathway in chicken DF-1 cells. Ectopic expression of chTRIM25 together with chMDA5 or a deletion mutant version exclusively harboring the CARD domains (chMDA5 2CARD) enhances IFN-β and NF-ĸB promoter activation. Using co-immunoprecipitation assays, we show that chMDA5 interacts with chTRIM25 through the CARD domains. Moreover, chTRIM25 co-localizes with both chMDA5 and chMDA5 2CARD, but not with chMDA5 mutant proteins partially or totally lacking these domains. On the other hand, ablation of endogenous chTRIM25 expression reduces chMDA5-induced IFN-β and NF-ĸB promoter activation. Interestingly, ectopic expression of either wild-type chTRIM25, or a mutant version (chTRIM25 C59S/C62S) lacking the E3 ubiquitin ligase activity, restores the co-stimulatory effect of chMDA5 in chTRIM25 knockout cells, suggesting that the E3-ubiquitin ligase activity of chTRIM25 is not required for its downstream IFN-β and NF-ĸB activating function. Also, IBDV-induced expression of IFN-β, Mx and OAS genes was reduced in chTRIM25 knockout as compared to wild-type cells, hence contributing to the enhancement of IBDV replication. Enhanced permissiveness to replication of other viruses, such as avian reovirus, Newcastle disease virus and vesicular stomatitis virus was also observed in chTRIM25 knockout cells. Additionally, chTRIM25 knockout also results in reduced MAVS-induced IFN-β promoter stimulation. Nonetheless, similarly to its mammalian counterpart, chTRIM25 overexpression in wild-type DF-1 cells causes the degradation of ectopically expressed chMAVS.

Chronic obstructive lung diseases as a risk factor for severe COVID-19 (review)

The review presents meta-analyses and original studies data of severe outcomes of COVID-19 infection in patients with chronic obstructive pulmonary disease.&#x0D; The main risk factors for the severe course of COVID-19 in many studies have been identified as follows: age over 65 years, chronic lung diseases, systemic arterial hypertension, cardiovascular diseases, diabetes mellitus, immunosuppression, chronic kidney and liver diseases. It was shown that patients with concomitant respiratory diseases were 4.2 times more likely to have a severe course of COVID-19 (OR 4.21; 95% CI 2.96.0), especially in patients with chronic obstructive pulmonary disease (OR 5.8, 95% CI 3.98.5). Patients with bronchial asthma also more often received mechanical ventilation (OR 1.58; 95% CI 1.022.44; p = 0.04), treatment in intensive care units (OR 1.58; 95% CI 1.092.29; p = 0.02), had longer hospital stays (OR 1.30; 95% CI 1.091.55; р 0.003) and higher mortality (OR 1.53; 95 % CI 1.012.33; p = 0.04) compared with COVID-19 patients without asthma or other chronic obstructive pulmonary diseases. Another factor contributing to severe outcomes of COVID-19 is tobacco use, which increases the risk of severe disease, hospitalization and poor outcomes.&#x0D; Patients with chronic obstructive pulmonary diseases, especially smokers, were more likely to have a severe COVID-19 and adverse outcomes of this disease, which must be taken into account when prescribing treatment for coronavirus infection.

Natural Killer Cells in Chronic Lymphocytic Leukemia: Functional Impairment and Therapeutic Potential

Immunotherapy approaches have advanced rapidly in recent years. While the greatest therapeutic advances so far have been achieved with T cell therapies such as immune checkpoint blockade and CAR-T, recent advances in NK cell therapy have highlighted the therapeutic potential of these cells. Chronic lymphocytic leukemia (CLL), the most prevalent form of leukemia in Western countries, is a very immunosuppressive disease but still shows significant potential as a target of immunotherapy, including NK-based therapies. In addition to their antileukemia potential, NK cells are important immune effectors in the response to infections, which represent a major clinical concern for CLL patients. Here, we review the interactions between NK cells and CLL, describing functional changes and mechanisms of CLL-induced NK suppression, interactions with current therapeutic options, and the potential for therapeutic benefit using NK cell therapies.

Current Epidemiology and Co-Infections of Avian Immunosuppressive and Neoplastic Diseases in Chicken Flocks in Central China.

The avian immunosuppressive and neoplastic diseases caused by Marek's disease virus (MDV), avian leucosis virus (ALV), and reticuloendotheliosis virus (REV) are seriously harmful to the global poultry industry. In recent years, particularly in 2020-2022, outbreaks of such diseases in chicken flocks frequently occurred in China. Herein, we collected live diseased birds from 30 poultry farms, out of 42 farms with tumour-bearing chicken flocks distributed in central China, to investigate the current epidemiology and co-infections of these viruses. The results showed that in individual diseased birds, the positive infection rates of MDV, ALV, and REV were 69.5% (203/292), 14.4% (42/292), and 4.7% (13/277), respectively, while for the flocks, the positive infection rates were 96.7% (29/30), 36.7% (11/30), and 20% (6/30), respectively. For chicken flocks, monoinfection of MDV, ALV, or REV was 53.3% (16/30), 3.3% (1/30), and 0% (0/30), respectively, but a total of 43.3% (13/30) co-infections was observed, which includes 23.3% (7/30) of MDV+ALV, 10.0% (3/30) of MDV+REV, and 10.0% (3/30) of MDV+ALV+REV co-infections. Interestingly, no ALV+REV co-infection or REV monoinfection was observed in the selected poultry farms. Our data indicate that the prevalence of virulent MDV strains, partially accompanied with ALV and/or REV co-infections, is the main reason for current outbreaks of avian neoplastic diseases in central China, providing an important reference for the future control of disease.

COVID-19 Vaccines: An Updated Overview of Different Platforms.

Vaccination has been identified as a critical method of disease control in the context of the current COVID-19 pandemic. The goal of this review is to update information on vaccine development and to identify areas of concern that require further research. We reviewed the literature on the development of COVID-19 vaccines, their efficacy, and use in special populations, as well as current vaccination strategies. To date, 170 vaccines are in clinical development, with 41 being already approved for use in various countries. The majority of vaccines approved for human use are vector-, subunit-, DNA-, or mRNA-based vaccines, or inactivated viruses. Because of the ongoing mutation of the SARS-CoV-2 virus, well-studied vector vaccines are losing relevance due to the ability of new virus strains to bypass neutralizing antibodies. Simultaneously, PS-based vaccines are becoming more popular. There is mounting evidence that the immunogenicity of COVID-19 vaccines is linked to their clinical efficacy. This has resulted in a shift in vaccination strategies, as well as the use of booster doses and revaccination. Furthermore, vaccination restrictions for children, pregnant women, the elderly, and people with chronic immunosuppressive diseases have been lifted, allowing more people to be vaccinated. New data on vaccine safety, including the incidence of serious adverse events, have been collected. Despite significant advances in the development of and research on COVID-19 vaccines, many questions remain that require further investigation.

Urine protein electrophoresis as a prognostic factor in childhood nephrotic syndrome relapse – An observational study in govt. medical college, Mulankunnathukavu, Thrissur

Childhood nephrotic syndrome (NS) is a chronic illness characterized by relapses and remissions. In many there will be disability, caused by the disease and from the treatment in the form of immunosuppression or end stage renal disease. Progression to renal failure will require anticipation for dialysis and/or renal transplant. A noninvasive biomarker such as urine protein profile that accurately predicts responsiveness to steroid therapy would be valuable in predicting the course of nephrotic syndrome. Our study tries to correlate between the selectivity of proteinuria and the outcome of relapses and thus prognosticate the course of the disease. Few similar studies have been done in India.Our study is a cross-sectional hospital based study, comprised of a population of 43 children with nephrotic syndrome relapse, between 1 and 14 years of age. Blood and urine samples were collected, to look for selective or nonselective proteinuria using the Agarose gel electrophoresis (Age) method. The treatment for relapse was started with steroid and, outcome was then related to the selectivity of proteinuria.Majority of our patients had non selective proteinuria (NSP) 60.5%, the rest had selective proteinuria (SP) 39.5%.There was a significant relation between nonselective proteinuria and- 1: Hypertension (p =0.049); 2: Low GFR p&amp;#60;0.001(p =0.0005); 3: Steroid dependent nephrotic syndrome. (p =0.0199).Non selective proteinuria was more in children, above the age of 6 years (p=0.001).The nonselective proteinuria group took more time for remission pointing to the lesser degree of steroid sensitivity.Non selective proteinuria can be used as a biomarker to predict the course in childhood nephrotic syndrome. The higher prevalence of non-selective proteinuria could be due to severe forms of nephrotic syndrome in our study. Selective proteinuria had a better outcome.

High antigenic diversity of serotype 1 infectious bursal disease virus revealed by antigenic cartography

The antigenic characterization of IBDV, a virus that causes an immunosuppressive disease in young chickens, has been historically addressed using cross virus neutralization (VN) assay and antigen-capture enzyme-linked immunosorbent (AC-ELISA). However, VN assay has been usually carried out either in specific antibody negative embryonated eggs, for non-cell culture adapted strains, which is tedious, or on chicken embryo fibroblasts (CEF), which requires virus adaptation to cell culture. AC-ELISA has provided crucial information about IBDV antigenicity, but this information is limited to the epitopes included in the tested panel with a lack of information of overall antigenic view. The present work aimed at overcoming those technical limitations and providing an extensive antigenic landscape based on original cross VN assays employing primary chicken B cells, where no previous IBDV adaptation is required. Sixteen serotype 1 IBDV viruses, comprising both reference strains and documented antigenic variants were tested against eleven chicken post-infectious sera. The VN data were analysed by antigenic cartography, a method which enables reliable high-resolution quantitative and visual interpretation of large binding assay datasets. The resulting antigenic cartography revealed i) the existence of several antigenic clusters of IBDV, ii) high antigenic relatedness between some genetically unrelated viruses, iii) a highly variable contribution to global antigenicity of previously identified individual epitopes and iv) broad reactivity of chicken sera raised against antigenic variants. This study provides an overall view of IBDV antigenic diversity. Implementing this approach will be instrumental to follow the evolution of IBDV antigenicity and control the disease.

Наблюдение пациентки с острым некрозом сетчатки в течение длительного периода времени

The medical and social significance of one of the most severe inflammatory diseases of the posterior segment of the eye, which includes acute retinal necrosis (ARN), is determined by the high degree of disability of patients. ARN occurs in somatically healthy people, but occurs more often among people suffering from immunosuppressive diseases or receiving immunosuppressive therapy. The diagnosis of ARN is made on the basis of clinical examination data according to the criteria developed in 1994 by the American Society of Uveitis Specialists. The prognosis of ARN is relatively unfavorable: the pathological process leads to practical blindness in 64 %, in 60 % there is a significant decrease in visual acuity. ARN is complicated by the development of retinal detachment in 65–75 %. Treatment of ARN includes intensive antiviral, anti-inflammatory, immunomodulatory therapy. Purpose: description of the observation of a patient with acute retinal necrosis over a long period of time. Material and methods. A long-term clinical observation of a patient with acute retinal necrosis for the period from 2008 to 2021 is presented. The patient underwent a standard ophthalmological examination, optical coherence tomography of the macular area, and ultrasound. Results. The development of ARN in the patient was observed after ARVI. Antiinflammatory treatment of ARN and surgical treatment of complications were carried out in the conditions of the academician S.N. Fyodorov Federal State Institution National Medical Research Center «Intersectoral Research and Technology Complex «Eye microsurgery» Ministry of Health of the Russian Federation», Novosibirsk Branch. The presented clinical case allows us to demonstrate the severe course of the pathological process and the development of serious complications. Timely conservative, laser and surgical treatment, active dynamic monitoring, despite the unfavorable prognosis for vision, made it possible to maintain residual vision in the patient. Conclusions. ARN is an important problem that requires further study and development of effective methods for early diagnosis, treatment and prevention of recurrence of this disease. Keywords: acute retinal necrosis; anti-inflammatory treatment

Sero-Prevalence and Risk Factors for Infectious Bursal Disease in Local Chicken on Backyard Production System in Selected Districts of Ilubabor Zone, South Western Ethiopia

Introduction Gumboro is an acute, highly contagious, and immunosuppressive viral disease of young chickens less than 17-weeks. However, in local chicken flocks of Ilubabor, there is no known sero-status of the disease. Methods To address this information gap, a cross-sectional study was conducted in local backyard chicken flocks of three districts of Ilubabor Zone where chick mortality and morbidity were a big problem. The objectives of the study were to estimate the seroprevalence of infectious bursal disease virus (IBDV) and to assess its risk factors. Result Out of 418 serum samples tested, 180 were positive and the overall chicken level seroprevalence of the IBDV antibody in the study area was found to be 43.10% (95% CI: 38.40-47.85) and flock-level seroprevalence was 45.63% (73/160) (95%CI: 37.91-53.34) with almost all test positive flock chickens were seropositive. Multivariable analysis at chicken level showed that the odds of IBDV seroprevalence was significantly high in Metu and Bilo Nopa districts, in purchased, in female and adult chickens. Also, it was high at flock level in chickens mixed with exotic breeds, in flocks having greater than 5 chickens. Conclusion This study shows that IBDV is circulating in the chicken population of Ilubabor at a high prevalence level. Therefore, further studies on serotypes and strains of IBDV identification should be carried out to design suitable control and prevention measures.

Fully Attenuated meq and pp38 Double Gene Deletion Mutant Virus Confers Superior Immunological Protection against Highly Virulent Marek's Disease Virus Infection.

Marek's disease virus (MDV) induces immunosuppression and neoplastic disease in chickens. The virus is controllable via an attenuated meq deletion mutant virus, which has the disadvantage of retaining the ability to induce lymphoid organ atrophy. To overcome this deficiency and produce more vaccine candidates, a recombinant MDV was generated from the highly virulent Md5BAC strain, in which both meq and a cytolytic replication-related gene, pp38, were deleted. Replication of the double deletion virus, Md5BAC ΔmeqΔpp38, was comparable with that of the parental virus in vitro. The double deletion virus was shown to be fully attenuated and to reduce lymphoid organ atrophy in vivo. Crucially, Md5BAC ΔmeqΔpp38 confers superior protection against highly virulent virus compared with a commercial vaccine strain, CVI988/Rispens. Transcriptomic profiling indicated that Md5BAC ΔmeqΔpp38 induced a different host immune response from CVI988/Rispens. In summary, a novel, effective, and safe vaccine candidate for prevention and control of MD caused by highly virulent MDV is reported. IMPORTANCE MDV is a highly contagious immunosuppressive and neoplastic pathogen. The virus can be controlled through vaccination via an attenuated meq deletion mutant virus that retains the ability to induce lymphoid organ atrophy. In this study, we overcame the deficiency by generating meq and pp38 double deletion mutant virus. Indeed, the successfully generated meq and pp38 double deletion mutant virus had significantly reduced replication capacity in vivo but not in vitro. It was fully attenuated and conferred superior protection efficacy against very virulent MDV challenge. In addition, the possible immunological protective mechanism of the double deletion mutant virus was shown to be different from that of the gold standard MDV vaccine, CVI988/Rispens. Overall, we successfully generated an attenuated meq deletion mutant virus and widened the range of potential vaccine candidates. Importantly, this study provides for the first time the theoretical basis of vaccination induced by fully attenuated gene-deletion mutant virus.