Immunization Strategies Research Articles

Poxin-deficient poxviruses are sensed by cGAS prior to genome replication.

Poxviruses are dsDNA viruses infecting a wide range of cell types, where they need to contend with multiple host antiviral pathways, including DNA and RNA sensing. Accordingly, poxviruses encode a variety of immune antagonists, most of which are expressed early during infection from within virus cores before uncoating and genome release take place. Amongst these antagonists, the poxvirus immune nuclease (poxin) counteracts the cyclic 2'3'-GMP-AMP (2'3'-cGAMP) synthase (cGAS)/stimulator of interferon genes DNA sensing pathway by degrading the immunomodulatory cyclic dinucleotide 2'3'-cGAMP, the product of activated cGAS. Here, we use poxviruses engineered to lack poxin to investigate how virus infection triggers the activation of STING and its downstream transcription factor interferon-responsive factor 3 (IRF3). Our results demonstrate that poxin-deficient vaccinia virus (VACV) and ectromelia virus (ECTV) induce IRF3 activation in primary fibroblasts and differentiated macrophages, although to a lower extent in VACV compared to ECTV. In fibroblasts, IRF3 activation was detectable at 10 h post-infection (hpi) and was abolished by the DNA replication inhibitor cytosine arabinoside (AraC), indicating that the sensing was mediated by replicated genomes. In macrophages, IRF3 activation was detectable at 4 hpi, and this was not affected by AraC, suggesting that the sensing in this cell type was induced by genomes released from incoming virions. In agreement with this, macrophages expressing short hairpin RNA (shRNA) against the virus uncoating factor D5 showed reduced IRF3 activation upon infection. Collectively, our data show that the viral genome is sensed by cGAS prior to and during genome replication, but immune activation downstream of it is effectively suppressed by poxin. Our data also support the model where virus uncoating acts as an immune evasion strategy to simultaneously cloak the viral genome and allow the expression of early immune antagonists.

Edwardsiella piscicida promotes mitophagy to escape autophagy-mediated antibacterial defense in teleost monocytes/macrophages

Edwardsiella piscicida is a Gram-negative intracellular pathogen. Currently, the immune evasion strategies of E. piscicida are not yet fully understood. In this study, we revealed that E. piscicida exploited mitophagy to enhance its intracellular survival in grass carp (Ctenopharyngodon idella) monocytes/macrophages. The results showed that in E. piscicida-infected cells, there was a significant loss of mitochondrial membrane potential and a marked increase in the production of mitochondrial reactive oxygen species (mtROS), indicating the damage to the mitochondria in the infected cells. Furthermore, fluorescence confocal images presented that E. piscicida infection elicited the colocalization of mitochondria with microtubule-associated protein 1 light chain 3 (LC3, a key marker molecule of autophagy) and lysosomes, suggesting the occurrence of mitophagy. This notion was supported by the findings that E. piscicida significantly stimulated LC3-II protein and damped Tom20 (a marker molecule of mitochondria) protein levels. Subsequently, a mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazine (CCCP) and a mitophagy inhibitor mitochondrial division inhibitor 1 (Mdivi-1) were used to evaluate the role of mitophagy in modulating the intracellular survival of E. piscicida. The results revealed that CCCP significantly promoted intracellular survival of E. piscicida, whereas Mdivi-1 hindered the bacterial growth. Moreover, Mdivi-1 further increased the production of bacteria-induced mitochondrial ROS in an additive manner. In particular, CCCP suppressed and Mdivi-1 promoted the colocalization of LC3-II with E. piscicida, implying that E. piscicida-triggered mitophagy to facilitate its growth probably by subverting the autophagy targeting this bacterium, a previously known clearance pathway of E. piscicida. Overall, our findings suggest a new survival strategy employed by E. piscicida within fish monocytes/macrophages.

Strengths and Weaknesses of Different Therapeutic Strategies for the Treatment of Patients with Multiple Myeloma Who Progress After the Frontline Use of Lenalidomide: A Narrative Review

Background/Objectives: Patients with multiple myeloma (MM) who relapse after exposure to lenalidomide in the context of their first-line therapy are becoming a growing and clinically relevant population. We performed a systematic review of available clinical trials evaluating the efficacy and safety of different therapeutic strategies for the treatment of patients with MM at first relapse after the frontline use of lenalidomide. Methods: Publications of interest were searched on the PubMed database. The following search terms were employed: relapsed multiple myeloma, refractory multiple myeloma, first relapse, second-line therapy, lenalidomide-refractory (Len-R) and lenalidomide-exposed (Len-Exp). Results: Overall, triplet regimens that included anti-CD38 antibodies, carfilzomib and dexamethasone achieved a more favorable PFS regardless of the number of prior therapies. Other trials also demonstrated a non-negligible benefit with combinations containing pomalidomide, particularly in early lines of therapy. However, the variable number of patients with Len-Exp/Len-R disease enrolled in these studies and the limited number of those analyzed after progression following frontline lenalidomide make it difficult to select an “optimal” choice for the treatment of patients with MM at first relapse. Promising results have been more recently obtained by using combo therapies, including belantamab mafodotin and, above all, immunotherapies with CAR-T cells, and ongoing clinical trials are exploring the role of bispecific antibodies and CELMoDs in this population of patients. Conclusions: In the absence of clear-cut data regarding the specific effects of available regimens on patients with MM who are refractory or have relapsed after first-line therapies including lenalidomide, novel approaches based on different types of immune strategies are expected to further improve the clinical outcome of these patients.

Abstract A017: Identifying proliferative and immune-modulatory drivers of small cell lung cancer (SCLC)

Abstract Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer that causes an estimated 200,000 patient deaths globally every year. Most (>70%) patients present with extensive stage (ES)-SCLC, and the disease primarily presents with a neuroendocrine (NE), immune-desert phenotype, with low expression of antigen-presenting machinery genes. Despite limited immune infiltration in the tumor, SCLC has reproducibly responded to immune checkpoint blockade. IMpower133 was a pivotal Phase III trial that added atezolizumab (anti-PD-L1) to platinum/etoposide chemotherapy for treatment of first-line ES-SCLC, which led to the first approval of an immune checkpoint blockade strategy in SCLC. While the inclusion of atezolizumab to the treatment regimen has extended the survival of some patients, SCLC remains an unmet medical need with a mOS of 12.3 months. Furthermore, we lack a deep molecular understanding of factors mediating response and resistance to standard of care therapies in SCLC. To understand the genetic drivers of SCLC that could be linked to immunotherapy resistance, we analyzed the matched whole-exome sequencing and RNA-seq data from baseline tumor samples collected from the IMpower133 trial. Previously, we applied the non-negative matrix factorization (NMF) approach to the RNA-seq data, which clustered patients into four subsets of SCLC, with varying degrees of immune infiltration, neuroendocrine program activation, and clinical benefit from immunotherapy. Notably, we identified an inflamed-neuroendocrine (I-NE) subset of patients that exhibit longer overall survival with chemoimmunotherapy compared to chemotherapy alone, and an inflamed-non-neuroendocrine (I-nonNE) subset of patients that did not show a similar benefit from the addition of immunotherapy to chemotherapy. Here, we interrogated the matched WES data for recurrent alterations that may identify subsets of tumors with distinct immunological features. We identified several genes whose alterations significantly affected the enrichment of immune-related gene signatures. In particular, we identified MANF and CSK, genes previously shown to be potential tumor suppressors, as genes whose alteration associates with an “immune desert” transcriptional program. Specifically, genetic deletions or low RNA expression was associated with significantly decreased gene expression of gene signatures associated with lymphocytes, macrophages, and antigen presentation machinery. These data suggest a potential mechanism by which commonly inactivated tumor suppressors may shape the “immune desert” phenotype of SCLC. Further work is needed to determine if and how these genes may directly or indirectly modulate the tumor-immune interaction. Citation Format: Myung Chang Lee, Velimir Gayevskiy, Stefanie Morris, Minu K Srivastava, Namrata S Patil, Stephen V Liu, Martin Reck, Sanjeev Mariathasan, David S Shames, David P MacPherson, Robert J Johnston, Barzin Y Nabet. Identifying proliferative and immune-modulatory drivers of small cell lung cancer (SCLC) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A017.

Exploring the role of aggrephagy-related signatures in immune microenvironment, prognosis, and therapeutic strategies of breast cancer.

Breast cancer (BC) is 1 of the most common malignant tumors among women globally. This study aimed to develop a prognostic signature based on aggrephagy-related genes (ARGs). Transcriptomic and clinical data for BC patients were downloaded from the cancer genome atlas and GEO databases. Differential expression analysis, univariate Cox proportional hazards regression and least absolute shrinkage and selection operator Cox regression were employed to construct a prognostic signature. Consensus clustering, evaluation of immune infiltration and drug sensitivity, and gene set enrichment analysis, and development of nomogram were performed. The expression of ARGs was validated using data from the Cancer Cell Line Encyclopedia and clinical samples. Eleven ARGs were abnormally expressed in BC, with 5 showing significant correlations with BC prognosis. Consensus clustering identified 2 molecular subtypes with distinct prognoses. A prognostic signature including 5 ARGs (VIM, TUBB1, TUBA3E, TUBA3D, TUBA1C) was developed, which showed high performance in predicting BC prognosis. The low-risk group showed enrichment in extracellular matrix organization and cell migration processes while chromosome separation was suppressed. Additionally, patients in this group also show activation in several signaling pathways including MAPK, PI3K-AKT, and cAMP pathways, whereas cell cycle and neutrophil extracellular trap formation were significantly inhibited. The signature was also associated with immune infiltration and drug sensitivity. A nomogram incorporating the risk signature, clinical stage and chemotherapy was constructed, demonstrating excellent performance in predicting prognosis. The expression of signature-related genes were validated in patients with BC. This study successfully constructed molecular subtypes and a prognostic signature based on ARGs in BC, and developed a nomogram.

Effectiveness and efficiency of immunisation strategies to prevent RSV among infants and older adults in Germany: a modelling study

BackgroundRecently, several novel RSV immunisation products that protect infants and older adults against RSV disease have been licensed in Europe. We estimated the effectiveness and efficiency of introducing these RSV immunisation strategies in Germany.MethodsWe used a Bayesian framework to fit a deterministic age-structured dynamic transmission model of RSV to sentinel surveillance and RSV-specific hospitalisation data in Germany from 2015 to 2019. The calibrated model was used to evaluate different RSV intervention strategies over 5 years: long-acting, single-dose monoclonal antibodies (mAbs) in high-risk infants aged 1–5 months; long-acting mAbs in all infants aged 1–5 months; seasonal vaccination of pregnant women and one-time seasonal vaccination of older adults (75 + /65 + /55 + years). We performed sensitivity analysis on vaccine uptake, seasonal vs. year-round maternal vaccination, and the effect of under-ascertainment for older adults.ResultsThe model was able to match the various RSV datasets. Replacing the current short-acting mAB for high-risk infants with long-acting mAbs prevented 1.1% of RSV-specific hospitalisations in infants per year at the same uptake. Expanding the long-acting mAB programme to all infants prevented 39.3% of infant hospitalisations per year. Maternal vaccination required a larger number to be immunised to prevent one additional hospitalisation than a long-acting mAB for the same uptake. Vaccination of adults older than 75 years at an uptake of 40% in addition to Nirsevimab in all infants prevented an additional 4.5% of all RSV hospitalisations over 5 years, with substantial uncertainty in the correction for under-ascertainment of the RSV burden.ConclusionsImmunisation has the potential to reduce the RSV disease burden in Germany.

Aptamer-based Immune Checkpoint Inhibition for Cancer Immunotherapy.

Cancer has long been a significant threat to human life and health. The advent of immune checkpoint blockade strategies has reversed cancer-induced immune suppression, advanced the development of immunotherapy, and offered new hope in the fight against cancer. Aptamers, which possess the same specificity and affinity as antibodies, are advantageous due to their synthetic accessibility and ease of modification, providing novel insights for immune checkpoint research. In this review, we outline the key aptamers currently developed for immune checkpoints such as CTLA-4, PD-1, PD-L1 and Siglec-15. We explore their potential in therapeutic strategies, including functionalizing or engineering aptamers for covalent binding, valency control, and nanostructure assembly, as well as investigating molecular mechanisms such as glycosylated protein functions and cell-cell interactions. Finally, the future applications of aptamers in immunotherapy are discussed.

PK205R targets the proximal element of IFN-I signaling pathway to assist African swine fever virus to escape host innate immunity at the early stage of infection.

African swine fever virus (ASFV) is a nuclear cytoplasmic large DNA virus (NCLDV) that causes devastating hemorrhagic diseases in domestic pigs and wild boars, seriously threatening the development of the global pig industry. IFN-I plays an important role in the body's antiviral response. Similar to other DNA viruses, ASFV has evolved a variety of immune escape strategies to antagonize IFN-I signaling and maintain its proliferation. In this study, we showed that the ASFV early protein pK205R strongly inhibited interferon-stimulated genes (ISGs) as well as the promoter activity of IFN-stimulated regulatory elements (ISREs). Mechanistically, pK205R interacted with the intracellular domains of IFNAR1 and IFNAR2, thereby inhibiting the interaction of IFNAR1/2 with JAK1 and TYK2 and hindering the phosphorylation and nuclear translocation of STATs. Subsequently, we generated a recombinant strain of the ASFV-pK205R point mutation, ASFV-pK205R7PM. Notably, we detected higher levels of ISGs in porcine alveolar macrophages (PAMs) than in the parental strain during the early stages of ASFV-pK205R7PM infection. Moreover, ASFV-pK205R7PM attenuated the inhibitory effect on IFN-I signaling. In conclusion, we identified a new ASFV immunosuppressive protein that increases our understanding of ASFV immune escape mechanisms.

Nervous system guides behavioral immunity in Caenorhabditis elegans.

Caenorhabditis elegans is a versatile model organism for exploring complex biological systems. Microbes and the external environment can affect the nervous system and drive behavioral changes in C. elegans. For better survival, C. elegans may develop behavioral immunity to avoid potential environmental pathogens. However, the molecular and cellular mechanisms underlying this avoidance behavior are not fully understood. The dissection of sensorimotor circuits in behavioral immunity may promote advancements in research on the neuronal connectome in uncovering neuronal regulators of behavioral immunity. In this review, we discuss how the nervous system coordinates behavioral immunity by translating various pathogen-derived cues and physiological damage to motor output in response to pathogenic threats in C. elegans. This understanding may provide insights into the fundamental principles of immune strategies that can be applied across species and potentially contribute to the development of novel therapies for immune-related diseases.

Evaluation of a Low-Temperature Immersion Immunization Strategy for the Infectious Spleen and Kidney Necrosis Virus orf037l Gene-Deleted Attenuated Vaccine

Background: Infectious spleen and kidney necrosis virus (ISKNV) poses a significant threat to aquaculture sustainability, particularly affecting mandarin fish (Siniperca chuatsi) and causing significant economic losses. Methods: To address this challenge, this study developed an ISKNV Δorf037l vaccine strain, where the orf037l gene was knocked out. Infection assays conducted at 28 °C showed that the knocking out the orf037l gene decreased the virulence of ISKNV and reduced lethality against mandarin fish by 26.7% compared to wild-type ISKNV. To further diminish residual virulence, the effect of low-temperature (22 °C) immersion immunization was evaluated. Results: The results indicate that low temperature significantly diminished the virulence of the Δorf037l vaccine strain, elevating the survival rate of mandarin fish to 90%. Furthermore, the vaccine strain effectively triggered the expression of crucial immune-related genes, such as IFN-h, IL-1, IκB, Mx, TNF-α, and Viperin, while inducing the production of specific neutralizing antibodies. Low-temperature immersion with Δorf037l achieved a high relative percentage of survival of 92.6% (n = 30) in mandarin fish, suggesting the potential of Δorf037l as a promising immersion vaccine candidate. Conclusions: These findings contribute to advancing fish immersion vaccine development and demonstrate the importance and broad applicability of temperature optimization strategies in vaccine development. Our work carries profound implications for both the theoretical understanding and practical application in aquaculture disease control.

How lactate affects immune strategies in lymphoma.

Tumor cells undergo metabolic reprogramming through shared pathways, resulting in a hypoxic, acidic, and highly permeable internal tumor microenvironment (TME). Lactate, once only regarded as a waste product of glycolysis, has an inseparable dual role with tumor immunity. It can not only provide a carbon source for immune cells to enhance immunity but also help the immune escape through a variety of ways. Lymphoma also depends on the proliferation signal of TME. This review focuses on the dynamic process of lactate metabolism and immune function changes in lymphoma and aims to comprehensively summarize and explore which genes, transcription factors, and pathways affect the biological changes and functions of immune cells. To deeply understand the complex and multifaceted role of lactate metabolism and immunity in lymphoma, the combination of lactate targeted therapy and classical immunotherapy will be a promising development direction in the future.

A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1-Based Malaria Vaccine versus RTS,S/AS01 in Murine Models.

Background/Objectives: We developed a multistage Plasmodium falciparum vaccine using a heterologous prime-boost immunization strategy. This involved priming with a highly attenuated, replication-competent vaccinia virus strain LC16m8Δ (m8Δ) and boosting with adeno-associated virus type 1 (AAV1). This approach demonstrated 100% efficacy in both protection and transmission-blocking in a murine model. In this study, we compared our LC16m8∆/AAV1 vaccine, which harbors a gene encoding Pfs25-PfCSP fusion protein, to RTS,S/AS01 (RTS,S) in terms of immune responses, protective efficacy, and transmission-blocking activity (TBA) in murine models. Methods: Mice were immunized following prime-boost vaccine regimens m8∆/AAV1 or RTS,S and challenged with transgenic Plasmodium berghei parasites. Immune responses were assessed via ELISA, and TB efficacy was evaluated using direct feeding assays. Results: m8∆/AAV1 provided complete protection (100%) in BALB/c mice and moderate (40%) protection in C57BL/6 mice, similar to RTS,S. Unlike RTS,S's narrow focus (repeat region), m8∆/AAV1 triggered antibodies for all PfCSP regions (N-terminus, repeat, and C-terminus) with balanced Th1/Th2 ratios. Regarding transmission blockade, serum from m8∆/AAV1-vaccinated BALB/c mice achieved substantial transmission-reducing activity (TRA = 83.02%) and TB activity (TBA = 38.98%)-attributes not observed with RTS,S. Furthermore, m8∆/AAV1 demonstrated durable TB efficacy (94.31% TRA and 63.79% TBA) 100 days post-immunization. Conclusions: These results highlight m8∆/AAV1's dual action in preventing sporozoite invasion and onward transmission, a significant advantage over RTS,S. Consequently, m8∆/AAV1 represents an alternative and a promising vaccine candidate that can enhance malaria control and elimination strategies.

Comparative analysis of meningeal transcriptomes in birds: Potential pathways of resilience to repeated impacts.

The meninges and associated vasculature (MAV) play a crucial role in maintaining cerebral integrity and homeostasis. Recent advances in transcriptomic analysis have illuminated the significance of the MAV in understanding the complex physiological interactions at the interface between the skull and the brain after exposure to mechanical stress. To investigate how physiological responses may confer resilience against repetitive mechanical stress, we performed the first transcriptomic analysis of avian MAV tissues using the Downy Woodpecker (Dryobates pubescens) and Tufted Titmouse (Baeolophus bicolor) as the comparison species. Our findings reveal divergences in gene expression profiles related to immune response, cellular stress management, and protein translation machinery. The male woodpeckers exhibit a tailored immune modulation strategy that potentially dampens neuroinflammation while preserving protective immunity. Overrepresented genes involved in cellular stress responses suggest enhanced mechanisms for mitigating damage and promoting repair. Additionally, the enrichment of translation-associated pathways hints at increased capacity for protein turnover and cellular remodeling vital for recovery. Our study not only fills a critical gap in avian neurobiology but also lays the groundwork for research in comparative neuroprotection.

Immunogenic Sulfated l-Idose Homo Oligosaccharides Elicit Neutralizing Antibody against Native Heparan Sulfate with Biomarker and Therapeutic Possibilities.

Heparan sulfate (HS) is a non-immunogenic antigen, and developing antibodies against specific sulfated patterns in HS poses significant challenges. Herein, we employed an innovative immunization strategy that exploits the molecular mimicry of HS to generate antibodies against HS sequences. Mice were immunized with synthetic sulfated oligo-l-idose (ID49) that mimics optimum 67% of the conserved structure of HS ligands. This immunization of ID49@CRM197 with alum and Freund's adjuvant resulted in the production of robust IgG antibody responses targeting ID49 and cross-reactivity with the N-sulfated HS ligands compared to N-unsubstituted and N-acetate domain synthetic HS ligands. Such a pharmacological agent exhibited distinct staining of tissue sections and cell lines and induced complement-dependent cell cytotoxicity against SK-BR-3 cancer cells. Moreover, these antibodies inhibited heparin-mediated anticoagulation activity similar to that of protamine. These findings highlight the biomarker and possible therapeutic capability of the antibodies.

Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy.

The immune system presents significant obstacles to gene therapy, which has limited its use in treating many illnesses. New approaches are needed to overcome these problems and improve the effectiveness of gene therapy. This study explores several techniques to immune regulation within gene therapy, a cutting-edge discipline that aims to optimise results by fine-tuning the immune response. We cover new ways to control the immune system and deliver therapeutic genes just where they are needed, including influencing immunological checkpoints, causing immunotolerance, and making smart use of immunomodulatory drugs. In addition, the study provides insight into new developments in the design of less immunogenic gene delivery vectors, which allow for the extension of transgene expression with minimal adverse immune reactions. In order to maximise the efficacy of gene-based therapies, this review analyses these novel approaches and gives a thorough overview of the present state of the art by addressing obstacles and pointing the way toward future developments in immune regulation. Not only does their integration provide new opportunities for the creation of safer and more effective gene treatments, but it also contains the key to overcome current obstacles.

Immunoglobulin M-based local production in skin-associated lymphoid tissue of flounder (Paralichthys olivaceus) initiated by immersion with inactivated Edwardsiella tarda

Fish skin, the mucosal site most exposed to external antigens, requires protection by an efficient local mucosal immune system. The mucosal reserve of IgM is recognized as an immune strategy that blocks pathogen invasion to maintain homeostasis, whereas the mechanism of skin-associated local IgM production induced by mucosal antigens is not well know. In this study, we found that the skin of flounder (Paralichthys olivaceus) was equipped with the immune cellular and molecular basis for processing mucosal antigens and triggering local specific responses, i.e., CD4+ Zap-70+ T cells, CD4- Zap-70+ T/NK cells, IgM+ MHCII+ B cells, PNA+ MHCII+ antigen-presenting cells, UEA-1+ WGA+ and UEA-1+ WGA- antigen-sampling cells, as well as secreted IgM and pIgR, as demonstrated by indirect immunofluorescence assay using different antibodies and lectins. After immersion immunization with inactivated Edwardsiella tarda, qPCR assay displayed up-regulation of immune-related genes in flounder skin. Flow cytometry analysis and EdU labeling demonstrated that the mucosal inactivated vaccine induced local proliferation and increased amounts of cutaneous IgM+ B cells. Skin explant culture proved the local production of specific IgM in the skin, which could bind to the surface of E. tarda. ELISA, laser scanning confocal microscopy, and western blot revealed that, in addition to the elevated IgM levels, pIgR protein level was significantly up-regulated in skin tissue and surface mucus containing the pIgR (secretory component, SC)-tetrameric IgM complex, indicating that mucosal vaccine stimulated up-regulation of IgM and pIgR, which were secreted as a complex into skin mucus to exert the protective effects as secretory IgM. These findings deepen the understanding of IgM-based local responses in the mucosal immunity of teleosts, which will be critical for subsequent investigation into the protective mechanism of mucosal vaccines for fish health.

Current vaccination and immunization strategies in dermatology

Vaccinations are an important pillar of public health. They have high benefits for individuals and society as awhole by specifically preventing or mitigating infectious diseases. In many cases, they offer benefits that go beyond protection against the disease in question, e.g., protective cardiovascular effects. Vaccination recommendations in Germany are drawn up by the Standing Committee on Vaccination (STIKO), while the European Medicines Agency (EMA) is responsible for the approval of vaccines in the EU. Vaccinations may be carried out by physicians regardless of their specialty. In dermatology, vaccinations against varicella (chickenpox), herpes zoster, and human papillomavirus are established. The development of vaccines against other dermatologically relevant diseases and cancer vaccines is the subject of intensive research. Particularly in the case of immunosuppression, the physician must also take into consideration which vaccinations are possible and useful or contraindicated. TypeI or typeIV allergies to components of vaccinations are very rare, but reactions at the injection site often occur as adermatological side effect. Urticarial reactions are also possible, as does the worsening of underlying dermatological conditions such as psoriasis vulgaris.

Potent efficacy of an IgG-specific endoglycosidase against IgG-mediated pathologies.

Endo-β-N-acetylglucosaminidases (ENGases) that specifically hydrolyze the Asn297-linked glycan on immunoglobulin G (IgG) antibodies, the major molecular determinant of fragment crystallizable (Fc) γ receptor (FcγR) binding, are exceedingly rare. All previously characterized IgG-specific ENGases are multi-domain proteins secreted as an immune evasion strategy by Streptococcus pyogenes strains. Here, using in silico analysis and mass spectrometry techniques, we identified a family of single-domain ENGases secreted by pathogenic corynebacterial species that exhibit strict specificity for IgG antibodies. By X-ray crystallographic and surface plasmon resonance analyses, we found that the most catalytically efficient IgG-specific ENGase family member recognizes both protein and glycan components of IgG. Employing invivo models, we demonstrated the remarkable efficacy of this IgG-specific ENGase in mitigating numerous pathologies that rely on FcγR-mediated effector functions, including T and B lymphocyte depletion, autoimmune hemolytic anemia, and antibody-dependent enhancement of dengue disease, revealing its potential for treating and/or preventing a wide range of IgG-mediated diseases in humans.

Role of Antibodies and Their Specificities in Atherosclerotic Cardiovascular Disease.

Atherosclerosis is a lipid-driven chronic inflammatory disease that is modulated by innate and adaptive immunity including humoral immunity. Importantly, antibody alterations achieved by genetic means or active and passive immunization strategies in preclinical studies can improve or aggravate atherosclerosis. Additionally, a wide range of epidemiological data demonstrate not only an association between the total levels of different antibody isotypes but also levels of antibodies targeting specific antigens with atherosclerotic cardiovascular disease. Here, we discuss the potential role of atherogenic dyslipidemia on the antibody repertoire and review potential antibody-mediated effector mechanisms involved in atherosclerosis development highlighting the major atherosclerosis-associated antigens that trigger antibody responses.

Atypical Mumps; are We Heading Towards an Outbreak?

Mumps, caused by the mumps virus, is a contagious disease primarily affecting children and young adults. While typically presenting with salivary gland swelling and systemic symptoms, mumps can lead to various complications including SNHL, orchitis/ oophoritis, aseptic meningitis. Recent observations suggest atypical features in mumps cases, raising concerns of a potential outbreak in India. To discuss the etiopathogenesis and clinical presentation in cases of atypical mumps with increasing number of cases, a prospective multicentric study was conducted across five major centers - SMS Medical College Jaipur, RDBP Jaipuria Hospital, Jaipur, Shri Ashwini Saxena ENT Hospital Rewari, AIIMS Bhubaneswar and SP Medical College Bikaner, in India to evaluate patients with acute salivary gland swellings. Clinical and laboratory data were collected, including demographics, presenting symptoms, history of vaccination, imaging findings, and treatment outcomes. Patients were followed for four weeks post-treatment to monitor for delayed complications. Among 53 patients, a bimodal age distribution was observed, with peaks in early adolescents and middle-aged individuals. Vaccination status was recorded based on recall. Fever and salivary gland swelling were predominant symptoms, with a significant proportion experiencing submandibular gland involvement. Elevated serum amylase and CRP levels correlated with disease severity and prolonged symptomatic resolution. Notably, cases of sensorineural hearing loss (SNHL) and airway complications emerged as significant concerns. The study highlights a shift in mumps demographics, with higher age groups affected and increased incidence of complications like SNHL and airway compromise. International trends also suggest periodic outbreaks and evolving clinical manifestations post-COVID-19 pandemic. Factors contributing to mumps resurgence include lack of vaccination or vaccine efficacy, population immunity, and seasonal variations. India appears to be facing a potential mumps outbreak, characterized by atypical features and increased risk of complications like SNHL and airway compromise. Serum amylase and CRP serve as valuable markers for disease severity. Early recognition and management of complications are crucial, emphasizing the importance of mumps immunization to mitigate the impact of the disease. ENT specialists should remain vigilant for emerging complications, particularly SNHL, advocating for comprehensive immunization strategies.