Injection Of Antigen Research Articles

Refractory shoulder injury related to vaccine administration: correlation with culture presence of Cutibacterium acnes

Shoulder pain following intramuscular administration of vaccine is common. However, a small number of patients experience prolonged pain and dysfunction atypical to normal transient postvaccination shoulder pain. Shoulder Injury Related to Vaccine Administration (SIRVA) remains incompletely understood, whether a robust immune response to vaccine antigen or inappropriate injection technique with needle placement in synovial or bursal tissue, or some combination of the two. Symptoms overlap with those of Cutibacterium acnes (C. acnes) infection but the relationship between the two, if any, has not been evaluated. Clinical case files were reviewed for 3 cases of SIRVA with positive cultures for C. acnes were reviewed. Presentation, treatment, and clinical outcomes were compared. In all cases, patients were thin (body mass index < 23), females, who had high injection placement of a vaccine, all patients had positive magnetic resonance imaging findings of increased signal in the subacromial bursa, and/or greater tuberosity. All patients underwent arthroscopic débridement and culture harvest and cultures were positive for C. acnes. A combination of oral and intravenous antibioticswas used, and all patients demonstrated clinical improvement from the preoperativestate. This case series presents 3 patients with refractory SIRVA who ultimately underwent arthroscopic irrigation and débridement with culture biopsy. Each case had culture results positive for C.acnes and all responded, at least partially, to arthroscopic débridement and intravenous antibiotic therapy. The purpose of this manuscript is to raise awareness of potential coexistence of SIRVA and C.acnes which may be of assistance to surgeons treating refractory cases of SIRVA.

Efficacy and safety of levilimab in combination with methotrexate in patients with active rheumatoid arthritis: 56-week results of phase III randomized double-blind placebo-controlled trial SOLAR

Background. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here we present 1-year efficacy and safety data of the SOLAR study.Objective – to evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA.Methods. The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021.154 adults, aged ≥18 years with confirmed diagnosis of RA were randomly assigned (2:1) to receive either levilimab (162 mg, SC, QW) + MTX (n=102) or placebo + MTX (n=52).After W24 of the study all subjects continued to receive open label levilimab. Subjects who have achieved DAS28-CRP≤2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP&gt;2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was done in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases.Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n=152).Results. Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP≤2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (&lt;2.6) and 7/27 (25.9%) achieved ACR/EULAR 2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP&lt;2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%).LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP≤2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52.The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%). blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%) and injection site reactions (5.9%). No deaths were occurred.Conclusions. Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to maintenance (Q2W) regimen in those who achieved remission of RA at week 24.

B cell receptor ligation induces IgE plasma cell elimination.

The proper regulation of IgE production safeguards against allergic disease, highlighting the importance of mechanisms that restrict IgE plasma cell (PC) survival. IgE PCs have unusually high surface B cell receptor (BCR) expression, yet the functional consequences of ligating this receptor are unknown. Here, we found that BCR ligation induced BCR signaling in IgE PCs followed by their elimination. In cell culture, exposure of IgE PCs to cognate antigen or anti-BCR antibodies induced apoptosis. IgE PC depletion correlated with the affinity, avidity, amount, and duration of antigen exposure and required the BCR signalosome components Syk, BLNK, and PLCγ2. In mice with a PC-specific impairment of BCR signaling, the abundance of IgE PCs was selectively increased. Conversely, BCR ligation by injection of cognate antigen or anti-IgE depleted IgE PCs. These findings establish a mechanism for the elimination of IgE PCs through BCR ligation. This has important implications for allergen tolerance and immunotherapy as well as anti-IgE monoclonal antibody treatments.

Synthesis and preclinical evaluation of novel 99mTc-labeled PSMA ligands for radioguided surgery of prostate cancer

BackgroundRadioguided surgery (RGS) has recently emerged as a valuable new tool in the management of recurrent prostate cancer (PCa). After preoperative injection of a 99mTc-labeled prostate-specific membrane antigen (PSMA) inhibitor, radioguided intraoperative identification and resection of lesions is facilitated by means of suitable γ-probes. First clinical experiences show the feasibility of RGS and suggest superiority over conventional lymph node dissection in recurrent PCa. However, commonly used [99mTc]Tc-PSMA-I&S exhibits slow whole-body clearance, thus hampering optimal tumor-to-background ratios (TBR) during surgery. We therefore aimed to develop novel 99mTc-labeled, PSMA-targeted radioligands with optimized pharmacokinetic profile to increase TBR at the time of surgery.MethodsThree 99mTc-labeled N4-PSMA ligands were preclinically evaluated and compared to [99mTc]Tc-PSMA-I&S. PSMA affinity (IC50) and internalization were determined on LNCaP cells. Lipophilicity was assessed by means of the distribution coefficient logD7.4 and an ultrafiltration method was used to determine binding to human plasma proteins. Biodistribution studies and static µSPECT/CT-imaging were performed at 6 h p.i. on LNCaP tumor-bearing CB17-SCID mice.ResultsThe novel N4-PSMA tracers were readily labeled with [99mTc]TcO4− with RCP > 95%. Comparable and high PSMA affinity was observed for all [99mTc]Tc-N4-PSMA-ligands. The ligands showed variable binding to human plasma and medium to low lipophilicity (logD7.4 − 2.6 to − 3.4), both consistently decreased compared to [99mTc]Tc-PSMA-I&S. Biodistribution studies revealed comparable tumor uptake among all [99mTc]Tc-N4-PSMA-ligands and [99mTc]Tc-PSMA-I&S, while clearance from most organs was superior for the novel tracers. Accordingly, increased TBR were achieved. [99mTc]Tc-N4-PSMA-12 showed higher TBR than [99mTc]Tc-PSMA-I&S for blood and all evaluated tissue. In addition, a procedure suitable for routine clinical production of [99mTc]Tc-N4-PSMA-12 was established. Labeling with 553 ± 187 MBq was achieved with RCP of 98.5 ± 0.6% (n = 10).ConclusionHigh tumor accumulation and favorable clearance from blood and non-target tissue make [99mTc]Tc-N4-PSMA-12 an attractive tracer for RGS, possibly superior to currently established [99mTc]Tc-PSMA-I&S. Its GMP-production according to a method presented here and first clinical investigations with this novel radioligand is highly recommended.

A comparative clinico-dermoscopic study of intralesional injection of combined digoxin and furosemide, Candida antigen, and vitamin D3 for multiple warts.

Immunostimulatory and antiproliferative therapies have been widely used for the treatment of multiple warts. Recently, anti-HPV activity of ionic contra viral therapy (ICVT) which is comprised of combined digoxin and furosemide has been demonstrated. To evaluate and compare the effectiveness and safety of intralesional injection of Candida antigen, vitamin D3, and combined digoxin and furosemide in the treatment of multiple warts. Seventy-five patients with numerous warts were randomly assigned to one of three equal groups: Candida antigen, vitamin D3, or a combination of digoxin and furosemide. In the Candida antigen group, injections into the biggest wart were done. In the vitamin D3 and combined digoxin/furosemide groups, the agent was injected into each wart with a maximum of five injected warts. Injections were repeated every 2 weeks until clearance or for a total of five sessions. There was a statistically significant difference in the overall therapeutic response among the studied groups in favor of the intralesional Candida antigen group (60%), followed by the vitamin D3 group (48%) and the ionic contraviral therapy group (28%) (p=0.02). However, the difference between both Candida antigen and vitamin D groups was not significant (p=0.59). Intralesional Candida antigen immunotherapy and vitamin D3 antiproliferative therapy are significantly more effective than ICVT. Short follow-up period and relatively small sample size.

Early IgE production is associated with accumulation of CD11b+ classical dendritic cells and CD11b+CD11c- macrophages in subcutaneous adipose tissue

In view of increased incidence of IgE-mediated diseases in Russia and worldwide, the efforts of various research groups are focused on studying the mechanisms that trigger the process of switching B-lymphocytes to IgE synthesis upon human exposure to harmless allergens, including the role of various antigen-presenting cells (APCs) in this process. However, the role of distinct APCs upon long-term penetration of low antigen doses via the tissue barriers, is yet poorly understood, as well as specific features of these events upon entrance of the antigen through the subcutaneous adipose tissue which contains tissueassociated lymphoid clusters (TALC).The aim of this work was to determine the relationship between the local accumulation of various APCs in the subcutaneous adipose tissue and development of early IgE production in a clinically relevant experimental model of allergy with long-term administration of low allergen doses. In this experimental model, specific IgE synthesis is induced, with minimal concomitant IgG production, thus mimicking the situation observed in patients with clinically sound allergies. BALB/c mice were immunized for 4 weeks subcutaneously in the withers area or intraperitoneally with low (100 ng) or high (10 μg) doses of the model allergen (ovalbumin). Blood samples were taken weekly from mice for ELISA testing, to determine the production of specific antibodies. Provocation tests were performed with high dose of the allergen, and adipose tissue samples were taken from the site of antigen injection for flow cytometric assays, in order to evaluate the contents of various APC subpopulations. Specific IgE production was induced mainly by subcutaneous injection of the antigen at low doses (100 ng) into the area of withers. When using this experimental regimen, we observed accumulation of classical CD11b+ cells in adipose tissue at the withers site, but not in the peritoneal adipose tissue, in absence of CD11b- classical, inflammatory or plasmacytoid, dendritic cells. These findings coincided in time with increased production of specific IgE on days +14 to +21. Accumulation of CD11b+CD11c- macrophages and their CD206+ M2 subpopulations at early terms (days +7 and +21) was also observed only after subcutaneous injection of the antigen into the withers area. The high-dose antigen injection (10 μg) which mediated IgG1 production to greater extent than production of IgE, led to earlier accumulation of CD11b+ classical dendritic cells (on day 7th), and to the absence of macrophage accumulation at later stages (day 21th). Thus, the early start of specific IgE production upon low-dose injection of the antigen into the subcutaneous adipose tissue may be associated with its presentation by CD11b+ classical dendritic cells in the presence of CD11b+CD11c- macrophages.

Effects of dietary aspirin supplementation on liver enzymes, immune response, cecum microflora and fatty acids profile in breast meat of broiler chickens

The present study was performed to investigate the effect of dietary aspirin (A) on broilers. A completely randomized design using 120 one-day-old male broiler chicks Ross 308, three levels of aspirin (0, 50, and 100 mg/kg) was used in 4 replicates, each including 10 chicks, during 42 days. The effects of different levels of aspirin, added to a basal diet, on blood plasma parameters, liver enzymes, immune system, cecal microflora, and fatty acids profile of breast muscle of chicks were investigated. Data analysis was performed by SAS statistical software and the comparison of the means with Duncan's test. The results showed that the effects of aspirin on blood parameters, liver enzymes of broilers (except for alkaline phosphatase which significantly reduced), the humoral immune system in response to antigen injection as sheep red blood cell (SRBC), antibody titer against Newcastle and influenza virus were not significant (P≥0.05). The highest percentage of neutrophils and eosinophils was related to this treatment. Also, aspirin treatments increased numerically the levels of unsaturated fatty acids and decreased saturated fatty acids. Moreover, aspirin led to a reduction in the population of Escherichia coli. So, based on the results of the present study, the use of 100 mg/kg aspirin in the diet of broilers is recommendable.

A Single-Administration Microneedle Skin Patch for Multi-Burst Release of Vaccine against SARS-CoV-2.

The necessity for multiple injections and cold-chain storage has contributed to suboptimal vaccine utilization, especially in pandemic situations. Thermally-stable and single-administration vaccines hold a great potential to revolutionize the global immunization process. Here, a new approach to thermally stabilize protein-based antigens is presented and a new high-throughput antigen-loading process is devised to create a single-administration, pulsatile-release microneedle (MN) patch which can deliver a recombinant SARS-CoV-2 S1-RBD protein-a model for the COVID-19 vaccine. Nearly 100% of the protein antigen could be stabilized at temperatures up to 100 °C for at least 1 h and at an average human body temperature (37 °C) for up to 4 months. Arrays of the stabilized S1-RBD formulations can be loaded into the MN shells via a single-alignment assembly step. The fabricated MNs are administered at a single time into the skin of rats and induce antibody response which could neutralize authentic SARS-CoV-2 viruses, providing similar immunogenic effect to that induced by multiple bolus injections of the same antigen stored in conventional cold-chain conditions. The MN system presented herein could offer the key solution to global immunization campaigns by avoiding low patient compliance, the requirement for cold-chain storage, and the need for multiple booster injections.

The efficacy and safety of intralesional Candida vaccine versus topical diphencyproprobenone in immunotherapy of verruca vulgaris: A randomized comparative study

Various therapeutic options are available for verruca. While physical destruction may be associated with scarring, immunotherapy may be effective in treating warts through stimulating body immune response. The objective of the study was to compare the efficacy, safety, and outcome of Candida antigen vs diphencyprone (DPCP) in the treatment of warts. Fifty patients were randomly assigned to receive either intralesional Candida antigen every 3 weeks or weekly DPCP application. Both treatments were applied only to the mother wart. Lesions’ clearance and associated side effects were observed up to 4 weeks after treatment. Two blinded physicians evaluated photos of warts before and 4 weeks after the end of treatment. Both modalities granted wart clearance and/or improvement with no statistically significant difference; however, Candida antigen was significantly better in clearing adjacent untreated warts (p = 0.046). Fewer side effects were observed among the Candida antigen group. The response was duration associated in the Candida groups only. Intralesional Candida antigen injection and DPCP treatments for warts yielded improvement with superiority of Candida injection in eradicating distant lesions and fewer side effects. A shorter wart duration may be associated with a better therapeutic response with Candida antigen.

Abnormal prostate microbiota composition is associated with experimental autoimmune prostatitis complicated with depression in rats.

BackgroundMicrobiota play essential roles in the pathogenesis of prostatitis and depression. However, the changes in prostate microbiota have not yet been explored in rats with prostatitis/depression. This study aimed to investigate the changes of prostate microbiota in rats with prostatitis/depression.MethodsRats with experimental autoimmune prostatitis (EAP) complicated with depression were constructed through injection of rat prostate antigen with immunoadjuvants followed by application of chronic unpredictable mild stress (CUMS). The rats were subjected to inflammatory factor detection and behavioral testing to confirm the establishment of the model. Subsequently, the prostate microbiota was assayed in the rats and compared by 16S rRNA gene sequencing.ResultsA rat model of EAP complicated with depression was established and confirmed by increases in IL-1β, IL-6, and TNF-α as well as the occurrence of depressive‐like behaviors. EAP/CUMS significantly altered the richness, evenness, and composition of prostate microbiota. Forty-six taxonomic biomarkers for prostate microbiota were enriched in rats with EAP/depression and exhibited statistically significant and biologically consistent differences. Metabolomics profiling revealed that EAP/depression was associated with reductive acetyl coenzyme A pathway, L-lysine fermentation to acetate and butanoate, protein N-glycosylation and purine nucleobases degradation I, which is regulated by DCE29, Nocardioes, Helicobacter and Dorea.ConclusionFindings from the study demonstrate the existence of abnormal prostate microbiota in EAP complicated with depression and may be helpful in the treatment of comorbid diseases of prostatitis and depression.

A megadiverse naïve library derived from numerous camelids for efficient and rapid development of VHH antibodies

The field of antibody development is under pressure to meet rising demands for speed, cost-effectiveness, efficacy, reliability, and large-scale production. It is costly and time-consuming to immunize animals and build a single-domain antibody (sdAb) library for each target. Using the variable domain (VHH) of heavy-chain only antibodies (HcAbs) derived from blood samples of 75 non-immunized camelid animals (51 alpacas, 13 llamas, 11 Bactrian camels), and spleens from two Bactrian camels, a naïve sdAb library with extensive megadiversity and reusability was constructed. The library was evaluated using next-generation DNA sequencing (NGS) and was found to contain hundreds of billions of unique clones. To confirm the availability of target-specific VHHs, a naive library was screened for a variety of targets. At least two VHH candidates were extracted for each target using a 20-day selection pipeline. Some binders had ultrahigh potencies, with binding affinities in the nanomolar range. This naïve library, in particular, offers the possibility of acquiring unique antibodies targeting antigens of interest with low feasible dissociation constant (kD) without the time, effort, and price associated in producing antibodies in animals via antigen injection. Overall, the study shows that the megadiverse naïve library provides a rapid, adaptable, and easy platform for antibody creation, emphasizing its therapeutic and diagnostic implications.

Enhancement of dendritic cellimmunotherapy by recalling antigens for hepatocellular carcinoma in mice.

Background: The therapeutic efficacy of dendritic cell (DC)-immunotherapy for large hepatoma in mice is unsatisfactory. Materials & methods: DC-based immunotherapy wasused to treat Hepa1-6 tumors measuring 6±1mm in diameter, enhanced by boosting tumor antigens. Results: CD4+ and CD8+ T-cells were contracted and transformed into memory phenotypic cells after DC-based vaccination. When T-cells were re-stimulated, T-cells obtained from mice boosted by tumor antigen injection showed highest proliferation capacity. When mice with large tumors were treated, DC-based vaccination boosted by tumor antigen and an additional DC-infusion yielded curative rates of 50% and 23.1%, respectively. Conclusion: DC vaccination inducedeffector memory cells. Antigen presentation recalled by DC or tumor antigens increased the curative rate in mice with large tumors.

34963 Psychosocial burden of verruca vulgaris: A cross-sectional survey

Although medically benign, common warts, or verruca vulagris, may negatively affect emotional wellbeing and quality of life (QoL). The various treatment options, such as liquid nitrogen cryotherapy or Candida antigen injection, can be painful, and repeat trials for wart resolution can be burdensome. Because the psychosocial burden of verruca is likely underestimated, we surveyed patients diagnosed and treated with warts at a single academic institution in an urban setting to assess the reported effects on QoL and satisfaction with the different treatment modalities. In domains such as anxiety, social activities and interpersonal relationships, patients rated impact of warts on a scale of 1-100, with a score of 1 representing “minimal impact” and 100 representing “severe impact.” These numerical ratings were then converted to the validated Dermatology Quality of Life Index (DLQI) parameters for consistency with other QoL studies. Our results indicate that patients are “A little” self-conscious or embarrassed by their warts and that their warts caused “A little” anxiety. Although patients reported more discomfort with Candida antigen than with cryotherapy, overall patient satisfaction for the two procedures was identical. Notably, 52% of respondents endorsed attempting home remedies before seeking clinical care, suggesting room for improvement in patient education for initiating dermatologic care. Future studies should examine patients with recalcitrant verruca and patient satisfaction with other management options, such as blistering agents.

Immunotherapy for type 1 diabetes mellitus by adjuvant-free Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP)

BackgroundType 1 diabetes mellitus (T1DM) is an autoimmune disease mediated by autoreactive T cells and dominated by Th1 response polarization. Insulin replacement therapy faces great challenges to this autoimmune disease, requiring highly frequent daily administration. Intriguingly, the progression of T1DM has proven to be prevented or attenuated by helminth infection or worm antigens for a relatively long term. However, the inevitable problems of low safety and poor compliance arise from infection with live worms or direct injection of antigens. Microneedles would be a promising candidate for local delivery of intact antigens, thus providing an opportunity for the clinical immunotherapy of parasitic products.MethodsWe developed a Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP) system, which serves as a new strategy to combat TIDM. In order to improve retention time and reduce contamination risk, a specific imperfection was introduced on the STAMP (asymmetric structure), which allows the tip to quickly separate from the base layer, improving reaction time and patient’s comfort. After loading Schistosoma japonicum-egg as the immune regulator, the effects of STAMP on blood glucose control and pancreatic pathological progression improvement were evaluated in vivo. Meanwhile, the immunoregulatory mechanism and biosafety of STAMP were confirmed by histopathology, qRT-PCR, ELISA and Flow cytometric analysis.ResultsHere, the newly developed STAMP was able to significantly reduce blood glucose and attenuate the pancreatic injury in T1DM mice independent of the adjuvants. The isolated Schistosoma japonicum-eggs micron slowly degraded in the skin and continuously released egg antigen for at least 2 weeks, ensuring localization and safety of antigen stimulation. This phenomenon should be attributed to the shift of Th2 immune response to reduce Th1 polarization.ConclusionOur results exhibited that STAMP could significantly regulate the blood glucose level and attenuate pancreatic pathological injury in T1DM mice by balancing the Th1/Th2 immune responses, which is independent of adjuvants. This technology opens a new window for the application of parasite products in clinical immunotherapy.

Mechanisms of formation of hybrid immunity in people who recovered from COVID-19 and were vaccinated with SARS-CoV-2 peptide antigens

The relevance of the current epidemic situation of a new coronavirus infection is determined by new strains of the virus and the registration of cases of re-infection in COVID-19 survivors earlier. In this regard, the questions about the expediency and nature of vaccination of those who have been ill attract close attention, moreover it has affected the formation of the concept of “hybrid immunity”. The aim of this study was to analyze changes in the parameters of the immune system, reflecting their regulatory and functional potential, in response to the introduction of the peptide vaccine EpiVacCorona to persons who have suffered from the new coronavirus infection. To study the features of the formation of hybrid immunity, a retrospective analysis of the observation of 43 study participants was carried out. The inclusion criteria were data confirming COVID-19 in mild and moderate forms of the course in the period from six months to a year ago, a low level or absence of antibodies to the nucleocapsid protein SARS-CoV-2, a negative PCR result for the presence of the SARS-CoV-2 virus, the absence of comorbid pathology. The subpopulation composition, regulatory and functional potential of the immune system were determined by flow cytofluorimetry using a set of monoclonal antibodies corresponding to the goals. 21 days after the administration of a single dose of EpiVacCorona, antibodies to the vaccine peptide antigens were registered in all study participants at the highest coefficient of positivity values for the SARS-CoV-2-IgG-Vector test system used. In addition, there was a fourfold increase in the number of specific IgG to the N protein. A specific immune response to recombinant SARS-CoV-2 antigens was accompanied by a decrease in the circulation of the number of monocytes expressing TLR4, T helper cells expressing the interaction coreceptor with antigen-presenting cells, unconnected B memory with an increase in the number of B lymphocytes expressing the CD40 T-B coreceptor interaction molecule. The remaining differences in the functioning of the immune system identified in patients with COVID-19 before the vaccination in comparison with the control data have not changed. The differences consist in a decrease in the proportion of monocytes expressing HLA-DR, an increase in the expression of interaction molecules on T and B lymphocytes, an increase in the number of Treg, B1 cells, activated B lymphocytes with a decrease in the proportion of suppressor Breg and B memory. The totality of the presented data demonstrates that the COVID-19 infection that preceded vaccination in mild and moderate clinical course contributes to the formation of immunological memory, which made it possible to form a secondary immune response even to a single injection of peptide antigens of the virus.

FRI465 - Intrabiliary injection of MAIT antigens induces cholangitis in mice

FRI465 - Intrabiliary injection of MAIT antigens induces cholangitis in mice

Characterization of proteome wide antigenic epitopes to design proteins specific and proteome-wide ensemble vaccines against heartland virus using structural vaccinology and immune simulation approaches

Heartland virus is a single-stranded negative-sense RNA virus that infects humans and causes lethargy, myalgia, headaches, nausea, diarrhea, weight loss, arthralgia, loss of appetite, leukopenia, and easy bruising due thrombocytopenia. The unavailability of antiviral drugs for HRTV infection is a major obstacle to treat this infection, therefore supportive care management is adopted in the case of a severe ailment. In this scientific study, proteins specific and proteome-wide Helper T-cell (HTL), linear B cell, and cytotoxic T-cell (CTL) epitopes mapping joined together with suitable linkers to design multi-epitopes subunit vaccine (MEVC). The constructed four vaccines from nucleocapsid protein, replicase, glycoprotein and finally whole proteome-wide constructs demonstrated stronger antigenic and non-allergenic behavior. Physiochemical properties evaluation also reported easy and efficient expression and downstream analysis of the constructs. Molecular docking of these constructs with toll-like receptor 7 (TLR7) revealed good binding and further validation based on MM/GBSA also demonstrated stronger interaction between the vaccine constructs and TLR7. Moreover, in silico cloning reported CAI value of 0.96 for each construct and excellent GC contents percentage required for experimental analysis. Furthermore, immune simulation-based immune response surveillance revealed that upon the injection of antigen the primary and secondary antibodies were produced between 5 and 15 days, and a more robust neutralization of the antigen by the proteome-wide vaccine construct was observed. This research could pave the way for the development of dynamic and efficient vaccines that contain a unique mix of numerous HRTV derived antigenic peptides to control HRTV infection.

Psychosocial Burden of Verruca Vulgaris: A Cross-Sectional Survey

Although medically benign, common warts, or verruca vulgaris, may negatively affect emotional wellbeing and quality of life (QoL). The various treatment options, such as liquid nitrogen cryotherapy or Candida antigen injection, can be painful, and repeat trials for wart resolution can be burdensome. Because the psychosocial burden of verruca is likely underestimated, we surveyed adult patients diagnosed and treated with warts at a single academic institution in an urban setting to assess the reported effects on QoL and satisfaction with the different treatment modalities. In domains such as anxiety, social activities, and interpersonal relationships, patients rated impact of warts on a scale of 1-100, with a score of 1 representing &ldquo;minimal impact&rdquo; and 100 representing &ldquo;severe impact.&rdquo; These numerical ratings were then converted to the validated Dermatology Life Quality Index (DLQI) parameters for consistency with other QoL studies. Our results indicate that patients are &ldquo;A little&rdquo; self-conscious or embarrassed by their warts and that their warts caused &ldquo;A little&rdquo; anxiety. Although patients reported more discomfort with Candida antigen than with cryotherapy, overall patient satisfaction for the two procedures was identical. Notably, 52% of respondents endorsed attempting home remedies before seeking clinical care, suggesting room for improvement in patient education for initiating dermatologic care. Future studies should examine patients with recalcitrant verruca and patient satisfaction with other management options. J Drugs Dermatol. 2022;21(6):614-617. doi:10.36849/JDD.6773.

Comparative study between intralesional injection of MMR, BCG, and candida albicans antigen in treatment of multiple recalcitrant warts.

Cutaneous warts represent a challenging condition to treat. To evaluate the safety and efficacy of intralesional injection of MMR (mumps, measles, and rubella) antigen, BCG (bacillus Calmette-Guerin) vaccine, and candida antigen for the treatment of multiple warts. A total of ninety (90) clinically confirmed adult patients complaining of recalcitrant extragenital warts of various sizes and durations were recruited in this randomized clinical trial. They were divided into three groups (A, B, and C). Each group consisted of (30) patients. Group (A) subjects received intralesional MMR injections. Group (B) subjects received intralesional BCG injection and Group (C) received intralesional candida antigen injection. Full clearance of warts was observed in (73.33%, 70%, and 43.33%) in groups A, B, and C, respectively. Infrequent side effects including pain, erythema, and minimal induration were reported in all groups but did not necessitate termination of treatment. All the three modalities used demonstrated a simple, safe modality with low adverse events, and with no recurrence. To achieve an optimal response with an ideal immunotherapeutic agent and ideal dose, further comparative studies are warranted and on different populations and larger sample sizes.

A meta-analysis of impacts of immune response and infection on oxidative status in vertebrates.

Inferring from patterns observed in biomedical research, ecoimmunological theory predicts that oxidative stress is a ubiquitous physiological cost that contributes to generating variation in immune function between individuals or species. This prediction is, however, often challenged by empirical studies testing the relationship between immune response or infection and oxidative status markers. This points out the importance of combining ecological immunology and oxidative stress ecology to further our understanding of the proximate causes and fitness consequences of individual variation in health, and adaptability to natural and anthropogenic environmental changes. I reviewed evidence and performed phylogenetic meta-analyses of changes in oxidative status markers owing to either injection of an antigen or infection in captive and free-living vertebrates (141 studies, 1262 effect sizes, 97 species). The dataset was dominated by studies on fish, birds and mammals, which provided 95.8% of effect sizes. Both antigen injection and parasite exposure were associated with changes of oxidative status. There were significant effects of taxonomic class and experimental environment (captivity vs. wild). In contrast with my predictions, age category (young vs. adult), study design (correlational vs. experimental) and proxies of pace of life (clutch size, litter size, and body mass; for birds and mammals only) were negligible in this dataset. Several methodological aspects (type of immunostimulant, laboratory assay, tissue analysed) showed significant effects on both strength and direction of effect. My results suggest that alterations of oxidative status are a widespread consequence of immune function across vertebrates. However, this work also identified heterogeneity in strength and direction of effect sizes, which suggests that immune function does not necessarily result in oxidative stress. Finally, this work identifies methodological caveats that might be relevant for the interpretation and comparability of results and for the application in conservation programs.