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To assess whether measles infection has an impact on the rate of non-measles infectious diseases over an extended period. This retrospective matched cohort study included 532 measles-diagnosed patients who were exactly matched with 2128 individuals without a previous measles diagnosis. Adjusted OR for any all-cause infectious diagnosis and any viral infection diagnosis ≤2 years after measles diagnosis between the measles and control groups was obtained from a conditional logistic regression model. The Cox proportional hazards model was used to estimate the hazard ratio. Previous measles virus (MeV) exposure was associated with an increased risk for all-cause non-measles infectious disease diagnosis (OR: 1.83, 95% CI: 1.26–2.64, p 0.001), with 492 diagnoses in the MeV-exposed group and 1868 diagnoses in the control group. Additionally, previous MeV exposure was linked to a higher risk of viral infection diagnosis (OR: 1.23, 95% CI: 1.01–1.59, p < 0.05), with 302 viral infection diagnoses in the MeV-exposed group and 1107 diagnoses in the control group. The hazard ratio for viral diagnosis in the MeV-exposed group compared with the control group was 1.54 (95% CI: 1.18–2.02, p < 0.001). Individuals diagnosed with measles had a moderately increased risk of being diagnosed with all-cause non-measles infectious disease or viral infection. This observational individual-level study supports previous ecological and individual population-level studies. [ABSTRACT FROM AUTHOR]

Urinary tumors pose a significant health threat because of their high prevalence and recurrence rates. Despite the availability of various treatment options, many patients poorly respond to traditional therapies, highlighting the urgent need for alternative approaches. Oncolytic viruses are promising therapeutic agents. These viruses exploit the unique characteristics of cancer cells to specifically target and destroy them, thereby triggering potent antitumor immune responses. This review delves into recent advancements and future prospects of oncolytic viruses, focusing on their application in renal, bladder, and prostate cancers. By discussing practical implications and the potential of different viruses, including the cowpox virus, adenovirus, measles virus, coxsackievirus, and reovirus, we pave the way for further exploration and refinement of this exciting field. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a progressive and catastrophic neurodegenerative disorder due to persistent infection with the aberrant measles virus in the brain. The exact etiology of SSPE is still unknown, and early diagnosis remains a challenge, especially with the atypical presentations. The pathogenesis of SSPE involves a complex interplay between viral factors and immunological response of the host. The presenting review demonstrates an extensive glimpse of the immuno‐genetics of SSPE, exploring the single‐nucleotide polymorphisms (SNPs), genetic risk factors and immune responses that influence susceptibility and disease progression. [ABSTRACT FROM AUTHOR]

Similar to other European countries, a measles epidemic dominated by D8 genotype strains is ongoing since 2022 in our country. Recent reports of liver involvement associated with new measles virus (MeV) strains are scarce. The aim of the study was to compare the clinical characteristics between hospitalized patients with measles from the current epidemic and those from the previous outbreak and to analyze the risk factors associated with hepatic involvement. Data were collected retrospectively for all consecutive adult (≥18 years old) patients admitted between October 2022–April 2024 and January 2018–December 2019. A number of 228 patients from the current and 130 from the previous MeV epidemic were included. The main statistically significant differences were those regarding hepatic involvement (77.2% vs. 45.4%, p < 0.001) and significant hepatocellular injury (23.6% vs. 10.7%, p = 0.003). Compared to cases without liver involvement (123), patients with hepatocytolysis (235) had a higher prevalence of keratoconjunctivitis (42.5% vs. 28.4%, p = 0.01), thrombocytopenia (47.6% vs. 34.9%, p = 0.02), severe lymphopenia (51% vs. 35.7%, p = 0.007) and high fibrinogen levels (58.7% vs. 47.1%, p = 0.04). MeV strains from the 2022–2024 epidemic were the strongest predictors of hepatic involvement in the multivariable analysis (odds ratio = 4.3, 95% confidence interval: 2.5–7.4, p < 0.001). The mortality rate of patients with hepatocellular injury was 1.2%. The current measles epidemic is dominated by high rates of hepatic involvement compared to the previous outbreak. Although not associated with a significant mortality, the potential change in MeV hepatotropism could have important clinical implications and warrants further monitoring. [ABSTRACT FROM AUTHOR]

Background: The therapeutic potential of oncolytic measles virotherapy has been demonstrated across various malignancies. However, the effectiveness against human breast cancer (BC) and the underlying mechanisms of the recombinant measles virus vaccine strain Hu191 (rMeV-Hu191) remain unclear. Methods: We utilized a range of methods, including cell viability assay, Western blot, flow cytometry, immunofluorescence, SA-β-gal staining, reverse transcription quantitative real-time PCR, transcriptome sequencing, BC xenograft mouse models, and immunohistochemistry to evaluate the antitumor efficacy of rMeV-Hu191 against BC and elucidate the underlying mechanism. Additionally, we employed transcriptomics and gene set enrichment analysis to analyze the lipid metabolism status of BC cells following rMeV-Hu191 infection. Results: Our study revealed the multifaceted antitumor effects of rMeV-Hu191 against BC. rMeV-Hu191 induced apoptosis, inhibited proliferation, and promoted senescence in BC cells. Furthermore, rMeV-Hu191 was associated with changes in oxidative stress and lipid homeostasis in infected BC cells. In vivo, studies using a BC xenograft mouse model confirmed a significant reduction in tumor growth following local injection of rMeV-Hu191. Conclusions: The findings highlight the potential of rMeV-Hu191 as a promising treatment for BC and provide valuable insights into the mechanisms underlying its oncolytic effect. [ABSTRACT FROM AUTHOR]

Pancreatic cancer presents formidable challenges due to rapid progression and resistance to conventional treatments. Oncolytic viruses (OVs) selectively infect cancer cells and cause cancer cells to lyse, releasing molecules that can be identified by the host's immune system. Moreover, OV can carry immune-stimulatory payloads such as interleukin-12, which when delivered locally can enhance immune system-mediated tumor killing. OVs are very well tolerated by cancer patients due to their ability to selectively target tumors without affecting surrounding normal tissues. OVs have recently been combined with other therapies, including chemotherapy and immunotherapy, to improve clinical outcomes. Several OVs including adenovirus, herpes simplex viruses (HSVs), vaccinia virus, parvovirus, reovirus, and measles virus have been evaluated in preclinical and clinical settings for the treatment of pancreatic cancer. We evaluated the safety and tolerability of a replication-competent oncolytic adenoviral vector carrying two suicide genes (thymidine kinase, TK; and cytosine deaminase, CD) and human interleukin-12 (hIL12) in metastatic pancreatic cancer patients in a phase 1 trial. This vector was found to be safe and well-tolerated at the highest doses tested without causing any significant adverse events (SAEs). Moreover, long-term follow-up studies indicated an increase in the overall survival (OS) in subjects receiving the highest dose of the OV. Our encouraging long-term survival data provide hope for patients with advanced pancreatic cancer, a disease that has not seen a meaningful increase in OS in the last five decades. In this review article, we highlight several preclinical and clinical studies and discuss future directions for optimizing OV therapy in pancreatic cancer. We envision OV-based gene therapy to be a game changer in the near future with the advent of newer generation OVs that have higher specificity and selectivity combined with personalized treatment plans developed under AI guidance. [ABSTRACT FROM AUTHOR]

Activation of the DNA-sensing STING axis by RNA viruses plays a role in antiviral response through mechanisms that remain poorly understood. Here, we show that the STING pathway regulates Nipah virus (NiV) replication in vivo in mice. Moreover, we demonstrate that following both NiV and measles virus (MeV) infection, IFNγ-inducible protein 16 (IFI16), an alternative DNA sensor in addition to cGAS, induces the activation of STING, leading to the phosphorylation of NF-κB p65 and the production of IFNβ and interleukin 6. Finally, we found that paramyxovirus-induced syncytia formation is responsible for loss of mitochondrial membrane potential and leakage of mitochondrial DNA in the cytoplasm, the latter of which is further detected by both cGAS and IFI16. These results contribute to improve our understanding about NiV and MeV immunopathogenesis and provide potential paths for alternative therapeutic strategies. Author summary: Viruses belonging to Paramyxoviridae family, such as Nipah and measles virus, represent a threat for public health due to recurring zoonotic spillover events or increasing epidemic episodes, respectively. In our previous work, we demonstrated the involvement of the DNA-sensing cGAS/STING axis of innate immunity in the control of Nipah and measles virus infections. However, the cellular and molecular mechanisms of STING activation by these RNA viruses remained obscure. Here, we show first that STING regulates Nipah virus infection in vivo and is activated both canonically and non-canonically by cGAS and IFI16 DNA sensors; respectively, during Paramyxovirus infections. Moreover, we describe that syncytia formation caused by both Nipah and measles viruses perpetrate mitochondrial perturbation, thus responsible for the leakage of DNA. Globally, we linked the events demonstrating that viral-induced syncytia formation triggers the leakage of mitochondrial DNA in the cytoplasm and its further sensing by cGAS and IFI16. [ABSTRACT FROM AUTHOR]

Background: Although a universal vaccine is available and Ethiopia is working outstandingly towards measles elimination, a recurrent measles outbreak has occurred each year in different parts of the country. Therefore, understanding the epidemiology of measles cases, the incidence of confirmed measles virus cases and related risk factors is crucial. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, measles incidence rate and risk factors for national measles infections occurring in the past two decades, from 2000 to 2023. Methods: Data from electronic databases, including PubMed, African Journal Online, WHO databases and Google Scholars, were searched to identify studies describing measles outbreaks, incidence rates and associated factors in Ethiopia that occurred between 2000 and 2023. Important basic information was extracted in an Excel spreadsheet and imported into Comprehensive Meta-analysis Software version 3 to evaluate the associations between measles outbreaks and different risk factors. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) for every included risk factor to evaluate the associations with measles outbreaks. Results: We included 36 studies involving 132,502 patients with confirmed measles cases in Ethiopia. The results of this systematic review and meta-analysis revealed that measles outbreaks were more frequently reported in the Oromia region (73,310 (33.1%)), followed by the Southern Nation Nationalities of Ethiopia region (29,057 (13.4%)). The overall pooled analysis indicated that the prevalence of measles susceptibility was 67.5% (95% CI: 67.3–67.8%), with an I2 of 99.86% and a p value for heterogeneity < 0.0001. The non-vaccinated status of the children, their contact history with measles cases, their travel history, the presence of cases in family or neighbors, and malnourished patients were identified as factors associated with the high prevalence and recurrent measles infections in Ethiopia. Conclusion: The results of this systematic review and meta-analysis indicated that the pooled prevalence of measles infection was high, which is a public health concern in Ethiopia. Thus, strengthening healthcare services, regular vaccination campaigns, and the integration of health education activities with other services may decrease the incidence rate. [ABSTRACT FROM AUTHOR]

Some negative-sense RNA viruses, including measles virus (MeV), share the characteristic that during their infection cycle, cytoplasmic inclusion bodies (IBs) are formed where components of the viral replication machinery are concentrated. As a foci of viral replication, how IBs act to enhance the efficiency of infection by affecting virus-host interactions remains an important topic of investigation. We previously established that upon MeV infection, the epigenetic host protein, WD repeat-containing protein 5 (WDR5), translocates to cytoplasmic viral IBs and facilitates MeV replication. We now show that WDR5 is recruited to IBs by forming a complex with IB-associated MeV phosphoprotein via a conserved binding motif located on the surface of WDR5. Furthermore, we provide evidence that WDR5 promotes viral replication by suppressing a major innate immune response pathway, the double-stranded RNA-mediated activation of protein kinase R and integrated stress response. IMPORTANCE MeV is a pathogen that remains a global concern, with an estimated 9 million measles cases and 128,000 measles deaths in 2022 according to the World Health Organization. A large population of the world still has inadequate access to the effective vaccine against the exceptionally transmissible MeV. Measles disease is characterized by a high morbidity in children and in immunocompromised individuals. An important area of research for negative-sense RNA viruses, including MeV, is the characterization of the complex interactome between virus and host occurring at cytoplasmic IBs where viral replication occurs. Despite the progress made in understanding IB structures, little is known regarding the virus-host interactions within IBs and the role of these interactions in promoting viral replication and antagonizing host innate immunity. Herein we provide evidence suggesting a model by which MeV IBs utilize the host protein WDR5 to suppress the protein kinase R-integrated stress response pathway. [ABSTRACT FROM AUTHOR]

Measles in persons with secondary vaccination failure (SVF) may be less infectious than cases in unvaccinated persons. Our systematic review aimed to assess transmission risk for measles after SVF. We searched PubMed, Embase, and Web of Science databases from their inception dates. Inclusion criteria were articles describing persons who were exposed to measles-infected persons who had experienced SVF. Across the included 14 studies, >3,030 persons were exposed to measles virus from SVF cases, of whom 180 were susceptible, indicating secondary attack rates of 0%–6.25%. We identified 109 cases of SVF from the studies; 10.09% (n = 11) of case-patients transmitted the virus, resulting in 23 further cases and yielding an effective reproduction number of 0.063 (95% CI 0.0–0.5). These findings suggest a remarkably low attack rate for SVF measles cases, suggesting that, In outbreak situations, public health management of unvaccinated persons could be prioritized over persons with SVF. [ABSTRACT FROM AUTHOR]

Despite the availability of an effective vaccine for several decades, the measles virus continues to spread worldwide. From 2018 to 2019, several countries experienced large measles outbreaks with genotype B3, including Tunisia. We analyzed 66 samples collected from serologically confirmed measles cases during this outbreak. Fifty-five percent were aged less than 12 months and had not received a measles vaccine. Phylogenetic analysis using the 450 nucleoprotein (N450) window revealed that all strains belonged to genotype B3, with five different variants identified. The N450 sequence of the predominant one, which circulated all through the epidemic period, was identical to the named strain MVs/Kabul.AFG/20.14/3. For better molecular discrimination, the amplification and sequencing of 1018 nucleotides in the non-coding region between the M and F genes (MF-NCRs) revealed higher variability with at least nine clusters. A phylogeographic study using Bayesian methods suggested the Governorate of Kasserine (on the borders of Algeria) as the introduction point with a TMRCA (Time to Most Recent Common Ancestor) for the 2019 sequences estimated around October 2018. These findings emphasize the crucial role of advanced molecular investigations in tracing measles transmission pathways which, together with good vaccine coverage, will help the final success of the global measles elimination program. [ABSTRACT FROM AUTHOR]

Intratumoural oncolytic virotherapy may have promise as a means to debulk and downstage inoperable tumours in preparation for successful surgery. Here, we describe the unique case of a 50-year-old self-experimenting female virologist with locally recurrent muscle-invasive breast cancer who was able to proceed to simple, non-invasive tumour resection after receiving multiple intratumoural injections of research-grade virus preparations, which first included an Edmonston-Zagreb measles vaccine strain (MeV) and then a vesicular stomatitis virus Indiana strain (VSV), both prepared in her own laboratory. The intratumoural virus therapy was well tolerated. Frequent imaging studies and regular clinical observations documenting size, consistency and mobility of the injected tumour demonstrate that both the MeV- and VSV-containing parts of the protocol contributed to the overall favourable response. Two months after the start of the virus injections, the shrunken tumour was no longer invading the skin or underlying muscle and was surgically excised. The excised tumour showed strong lymphocytic infiltration, with an increase in CD20-positive B cells, CD8-positive T cells and macrophages. PD-L1 expression was detected in contrast to the baseline PD-L1-negative phenotype. The patient completed one-year trastuzumab adjuvant therapy and remains well and recurrence-free 45 months post-surgery. Although an isolated case, it encourages consideration of oncolytic virotherapy as a neoadjuvant treatment modality. [ABSTRACT FROM AUTHOR]

Abstract Background Although a universal vaccine is available and Ethiopia is working outstandingly towards measles elimination, a recurrent measles outbreak has occurred each year in different parts of the country. Therefore, understanding the epidemiology of measles cases, the incidence of confirmed measles virus cases and related risk factors is crucial. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, measles incidence rate and risk factors for national measles infections occurring in the past two decades, from 2000 to 2023. Methods Data from electronic databases, including PubMed, African Journal Online, WHO databases and Google Scholars, were searched to identify studies describing measles outbreaks, incidence rates and associated factors in Ethiopia that occurred between 2000 and 2023. Important basic information was extracted in an Excel spreadsheet and imported into Comprehensive Meta-analysis Software version 3 to evaluate the associations between measles outbreaks and different risk factors. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) for every included risk factor to evaluate the associations with measles outbreaks. Results We included 36 studies involving 132,502 patients with confirmed measles cases in Ethiopia. The results of this systematic review and meta-analysis revealed that measles outbreaks were more frequently reported in the Oromia region (73,310 (33.1%)), followed by the Southern Nation Nationalities of Ethiopia region (29,057 (13.4%)). The overall pooled analysis indicated that the prevalence of measles susceptibility was 67.5% (95% CI: 67.3–67.8%), with an I2 of 99.86% and a p value for heterogeneity

Abstract Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of ‘help’ enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles.

Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of 'help' enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles. [ABSTRACT FROM AUTHOR]

Introduction: Tauopathies are a class of neurodegenerative disorders characterized by the abnormal accumulation of hyperphosphorylated tau protein in the brain. Subacute sclerosing panencephalitis (SSPE) caused by a latent aberrant measles virus infection, is characterized by extensive inflammation and neuronal impairment. A prominent pathological hallmark of SSPE described recently is the accumulation of abnormal tau protein possibly resulting from diffuse brain inflammation triggered by measles virus infection. Short summary: Understanding the role of tau pathophysiology in SSPE is crucial for improving the diagnosis and management of this debilitating condition. Current research suggests that persistent measles virus infection in the brain leads to chronic inflammation, which in turn triggers abnormal tau phosphorylation and accumulation. Further elucidating the precise mechanisms linking measles virus infection, neuro-inflammation, and tauopathy in SSPE is essential for developing targeted therapies. Conclusion: This narrative review provides valuable insights for both researchers and clinicians in understanding the pathological mechanisms underlying SSPE which is crucial for developing effective treatment strategies. These might include antiviral drugs to combat persistent infection, anti-inflammatory agents to reduce neuro-inflammation, or even treatments targeting tau pathology directly. Collaborative efforts among researchers, clinicians, and public health authorities are crucial for advancing our understanding of SSPE to combat this devastating disorder. [ABSTRACT FROM AUTHOR]

Moringa oleifera (M. oleifera) is a plant widely used for its beneficial properties both in medical and non-medical fields. Because they produce bioactive metabolites, plants are a major resource for drug discovery. In this study, two different cultivars of leaves of M. oleifera (Salento and Barletta) were obtained by maceration or microwave-assisted extraction (MAE). We demonstrated that extracts obtained by MAE exhibited a lower cytotoxic profile compared to those obtained by maceration at concentrations ranged from 25 to 400 µg/mL, on both Vero CCL-81 and Vero/SLAM cells. We examined their antiviral properties against two viruses, i.e., the human coronavirus 229E (HCoV-229E) and measles virus (MeV), which are both responsible for respiratory infections. The extracts were able to inhibit the infection of both viruses and strongly prevented their attack and entry into the cells in a range of concentrations from 50 to 12 µg/mL. Particularly active was the variety of Salento that registered a 50% inhibitory concentration (IC50) at 21 µg/mL for HCoV-229E and at 6 µg/mL for MeV. We identified the presence of several compounds through high performance liquid chromatography (HPLC); in particular, chlorogenic and neochlorogenic acids, quercetin 3-O-β-d-glucopyranoside (QGP), and glucomoringin (GM) were mainly observed. In the end, M. oleifera can be considered a promising candidate for combating viral infections with a very strong action in the early stages of viral life cycle, probably by destructuring the viral particles blocking the virus–cell fusion. [ABSTRACT FROM AUTHOR]

This review provides an overview of the canine distemper virus (CDV), a highly infectious pathogen causing severe disease in domestic dogs and wildlife. It shares genetic similarities with the human measles virus (HMV) in humans and the rinderpest virus (RPV) in cattle. The origin of CDV likely involves a mutation from human measles strains, possibly in the New World, with subsequent transmission to dogs. CDV has been globally observed, with an increasing incidence in various animal populations. Genomic mutations, especially in the H protein, contribute to its ability to infect different hosts. Diagnosis by molecular techniques like RT-qPCR offers rapid and sensitive detection when compared with serological tests. Genomic sequencing is vital for understanding CDV evolution and designing effective control strategies. Overall, CDV poses a significant threat, and genomic sequencing enhances our ability to manage and prevent its spread. Here, the epidemiology of CDV principally in Mexico is reviewed. [ABSTRACT FROM AUTHOR]

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute. [ABSTRACT FROM AUTHOR]

Background: Measles and rubella are vaccine-preventable diseases targeted for elimination in most World Health Organization regions, and China is considered to have momentum towards measles elimination. Therefore, this study aimed to assess the population immunity levels against measles and rubella in Zhejiang Province in China in order to provide valuable insights for informing future public health measures and contributing to the ongoing global campaign against these diseases. Materials and methods: A cross-sectional serological survey was conducted in 2022. A total of 2740 blood samples were collected from healthy individuals spanning the age range of 0–59 years, representing diverse demographic strata across 11 prefectures in Zhejiang Province in China. The sera were tested for measles and rubella IgG antibodies to determine positivity rates and geometric mean concentrations (GMCs). Results: The overall positivity rate for the measles IgG antibody was 85.3%, with a GMC of 588.30 mIU/mL. The positivity rate for the rubella IgG antibody was 70.9%, and the GMC was 35.30 IU/mL. Measles IgG antibody positivity rates across the 0–11 months, 12–23 months, 24–35 months, 3–5 years, 6–9 years, 10–14 years, 15–19 years, 20–29 years, and 30–59 years age groups were 63.1%, 92.5%, 97.0%, 94.0%, 85.8%, 77.3%, 86.9%, 84.9%, and 88.7%, respectively (trend χ2 = 118.34, p < 0.001). Correspondingly, rubella antibody positivity rates for these same age brackets were 55.9%, 87.9%, 94.7%, 88.2%, 69.9%, 54.2%, 72.6%, 67.5%, and 74.3% (trend χ2 = 199.18, p < 0.001). Both univariate and multivariate analyses consistently demonstrated that age, immunization history, and differing economic levels were significant factors contributing to variations in antibody levels. Conclusions: The seroprevalence of measles and rubella was lower than that required for herd immunity. Periodic vaccination campaigns should be launched to increase immunity. [ABSTRACT FROM AUTHOR]

More than 100 laboratories in the World Health Organization Global Measles and Rubella Laboratory Network (GMRLN) perform nucleic acid-based methods for case confirmation of measles or rubella infections and/or strain surveillance (genotyping). The quality of laboratory data is critical to ensure that diagnostic results and country reports to regional verification committees are based on accurate data. A molecular External Quality Assurance (mEQA) program was initiated by the US-CDC in 2014 to evaluate the performance of laboratories in the network. The inclusion of testing for measles and rubella viruses, with a focus on detection and genotyping, plus the diversity of assays and platforms employed required a flexible and comprehensive proficiency testing program. A stepwise introduction of new evaluation criteria gradually increased the stringency of the proficiency testing program, while giving laboratories time to implement the required changes. The mEQA program plays an important role in many processes in the GMRLN, including informing plans for the training of laboratory staff, access to reagents, and the submission of sequence data to global databases. The EQA program for Local Public Health Institutes in Japan is described as an example for national mEQA programs. As more laboratories initiate molecular testing, the mEQA will need to continue to expand and to adapt to the changing landscape for molecular testing. [ABSTRACT FROM AUTHOR]

This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal "counterparts" in a dual "One Health" and "Translational Medicine" perspective. Within this challenging context, special emphasis is placed upon Alzheimer's disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by "Subacute Sclerosing Panencephalitis" (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a "brain-only" form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human "analogues". [ABSTRACT FROM AUTHOR]

Canine distemper virus (CDV) belongs to morbillivirus, including measles virus (MeV) and rinderpest virus, which causes serious immunological and neurological disorders in carnivores, including dogs and rhesus monkeys, as recently reported, but their vaccines are highly effective. The attachment glycoprotein hemagglutinin (CDV-H) at the CDV surface utilizes signaling lymphocyte activation molecule (SLAM) and Nectin-4 (also called poliovirus-receptor-like-4; PVRL4) as entry receptors. Although fusion models have been proposed, the molecular mechanism of morbillivirus fusion entry is poorly understood. Here, we determined the crystal structure of the globular head domain of CDV-H vaccine strain at 3.2 Å resolution, revealing that CDV-H exhibits a highly tilted homodimeric form with a six-bladed ß-propeller fold. While the predicted Nectin-4-binding site is well conserved with that of MeV-H, that of SLAM is similar but partially different, which is expected to contribute to host specificity. Five N-linked sugars covered a broad area of the CDV-H surface to expose receptor-binding sites only, supporting the effective production of neutralizing antibodies. These features are common to MeV-H, although the glycosylation sites are completely different. Furthermore, real-time observation using high-speed atomic force microscopy revealed highly mobile features of the CDV-H dimeric head via the connector region. These results suggest that sugar-shielded tilted homodimeric structure and dynamic conformational changes are common characteristics of morbilliviruses and ensure effective fusion entry and vaccination. [ABSTRACT FROM AUTHOR]

Measles disease is caused by the measles virus (MV), which is a highly contagious viral infection that mainly affects children. Measles disease is one of the vaccine-preventable diseases, despite the availability of an effective vaccine, measles remains a significant public health concern globally. Understanding the immune responses to the MV is very important for the development of improved vaccines and therapeutic strategies. The aim of the current study is to summarize current knowledge on the innate and adaptive immune responses to measles infection, including the role of various immune system components; cells, cytokines, and antibodies. In addition to that, the paper discusses the immunological memory generated following measles infection or vaccination and its implications for long-term protection. [ABSTRACT FROM AUTHOR]

Primary bone malignancies, including osteosarcoma (OS), are rare but aggressive. Current OS treatment, involving surgical resection and chemotherapy, has improved survival for non-metastatic cases but remains ineffective for recurrent or metastatic OS. Oncolytic viral therapy (OVT) is a promising alternative, using naturally occurring or genetically modified viruses to selectively target and lyse cancer cells and induce a robust immune response against remaining OS cells. Various oncolytic viruses (OVs), such as adenovirus, herpes simplex virus, and measles virus, have demonstrated efficacy in preclinical OS models. Combining OVT with other therapeutics, such as chemotherapy or immunotherapy, may further improve outcomes. Despite these advances, challenges in reliability of preclinical models, safety, delivery, and immune response must be addressed to optimize OVT for clinical use. Future research should focus on refining delivery methods, exploring combination treatments, and clinical trials to ensure OVT's efficacy and safety for OS. Overall, OVT represents a novel approach with the potential to drastically improve survival outcomes for patients with OS. [ABSTRACT FROM AUTHOR]

Morbillivirus canis (canine distemper virus (CDV)) is recognized as a multihost pathogen responsible for a transmissible disease affecting both domestic and wild animals. A considerable portion of wildlife populations remain unvaccinated due to a lack of safety and immunogenicity data on existing vaccines for the prevention of CDV infection in these species. This review aimed to assess the current state of CDV vaccination research for both domestic and wild animals and to explore novel vaccine candidates through in vivo studies. It also sought to synthesize the scattered information from the extensive scientific literature on CDV vaccine research, identify key researchers in the field, and highlight areas where research on CDV vaccination is lacking. A scoping review was conducted across four databases following the PRISMA-ScR protocol, with information analyzed using absolute and relative frequencies and 95% confidence intervals (CIs) for study number proportions. Among the 2321 articles retrieved, 68 met the inclusion criteria and focused on CDV vaccines in various animal species, such as dogs, ferrets, minks, and mice. Most of the scientific community involved in this research was in the USA, Canada, France, and Denmark. Various vaccine types, including MLV CDV, recombinant virus, DNA plasmids, inactivated CDV, and MLV measles virus (MeV), were identified, along with diverse immunization routes and schedules employed in experimental and commercial vaccines. Safety and efficacy data were summarized. Notably, 37 studies reported postimmunization CDV challenge, primarily in dogs, revealing the survival rates of vaccinated animals. In summary, CDV vaccines generally demonstrate an acceptable safety profile in dogs and show promise as a means of controlling CDV. However, significant gaps in vaccine research persist, particularly concerning wildlife reservoirs, indicating the need for further investigation. [ABSTRACT FROM AUTHOR]

Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases in immunocompromised patients, identifying distinctive clinical and neuroimaging features. These findings could facilitate MIBE diagnosis without the need for brain biopsies. Our systematic review on MIBE and HIV-related SSPE adhered to PRISMA guidelines and was registered with PROSPERO. We searched multiple databases and followed a detailed inclusion process with independent reviews and quality assessment. Data on patient demographics, clinical features, and outcomes were compiled. A review of 39 studies on 49 MIBE patients and 8 reports on HIV-positive SSPE patients was conducted. Acute lymphoblastic leukemia, HIV, organ transplants, and malignancies were common precursors to MIBE. Perinatal HIV was prevalent among SSPE cases. Seizures were the primary symptom in MIBE, often drug-resistant and progressing to status epilepticus or epilepsia partialis continua, whereas periodic myoclonus was universal in SSPE. Neuroimaging showed distinct patterns for each group, and histopathology confirmed measles virus presence in 39% of MIBE cases. MIBE patients typically progressed to coma and death. In conclusion, MIBE and SSPE in HIV-infected patients present with distinct clinical pictures but identical brain pathological abnormalities. [ABSTRACT FROM AUTHOR]

Measles is the most contagious communicable disease, causing an estimated 5.5 million cases and more than 30,000 deaths in the Western Pacific Region (WPR) during 2000. Rubella infection in a pregnant woman can be devastating for the foetus, resulting in congenital rubella syndrome (CRS) in 90% of rubella infections in early pregnancy. It was estimated that approximately 9000 CRS cases occurred in the WPR in 2010. World Health Organization (WHO) Member States in the WPR decided in 2003 to eliminate measles and in 2014 to eliminate rubella from the region. While the WPR successfully attained historically low measles incidence in 2012, it experienced a region-wide measles resurgence in 2013–2016. During the regional resurgence, WHO and Member States accumulated greater knowledge on the epidemiology of measles and rubella in the WPR and strategies to maintain gains. The implementation of the resulting new regional strategy and plan of action from 2018 has proven that measles and rubella elimination is achievable and sustainable under the pressure of multiple importations of measles virus during the world-wide measles resurgences in 2018–2019. This article discusses this progress and achievements towards achieving the global eradication of measles and rubella. [ABSTRACT FROM AUTHOR]

Measles elimination refers to the interruption of measles virus transmission in a defined geographic area (e.g., country or region) for 12 months or more, and measles eradication refers to the global interruption of measles virus transmission. Measles eradication was first discussed and debated in the late 1960's shortly after the licensure of measles vaccines. Most experts agree that measles meets criteria for disease eradication, but progress toward national and regional measles elimination has slowed. Several paths to measles eradication can be described, including an incremental path through country-wide and regional measles elimination and phased paths through endgame scenarios and strategies. Infectious disease dynamic modeling can help inform measles elimination and eradication strategies, and all paths would be greatly facilitated by innovative technologies such as microarray patches to improve vaccine access and demand, point-of-contact diagnostic tests to facilitate outbreak responses, and point-of-contact IgG tests to identify susceptible populations. A pragmatic approach to measles eradication would identify and realize the necessary preconditions and clearly articulate various endgame scenarios and strategies to achieve measles eradication with an intensified and coordinated global effort in a specified timeframe, i.e., to "go big and go fast". To encourage and promote deliberation among a broad array of stakeholders, we provide a brief historical background and key considerations for setting a measles eradication goal. [ABSTRACT FROM AUTHOR]

The rapid development of potency assays is critical in the development of life-saving vaccines. The traditional plaque assay or fifty percent tissue culture infectious dose (TCID50) assay used to measure the potency of live virus vaccines is time consuming, labor intensive, low throughput and with high variability. Described here is the development and qualification of a cell-based reporter potency assay for two vaccines for respiratory viral infection, one based on the recombinant vesicular stomatitis virus (rVSV) backbone, termed Vaccine 1 in this paper, and the other based on the measles virus vector, termed Vaccine 2. The reporter potency assay used a Vero E6 cell line engineered to constitutively express NanuLuc® luciferase, termed the VeroE6-NLuc or JM-1 cell line. Infection of JM-1 cells by a live virus, such as rVSV or measles virus, causes a cytopathic effect (CPE) and release of NanuLuc® from the cytoplasm into the supernatant, the amount of which reflects the intensity of the viral infection. The relative potency was calculated by comparison to a reference standard using parallel line analysis (PLA) in a log–log linear model. The reporter assay demonstrated good linearity, accuracy, and precision, and is therefore suitable for a vaccine potency assay. Further evaluation of the Vaccine 1 reporter assay demonstrated the robustness to a range of deliberate variation of the selected assay parameters and correlation with the plaque assay. In conclusion, we have demonstrated that the reporter assay using the JM-1 cell line could be used as a potency assay to support the manufacturing and release of multiple live virus vaccines. [ABSTRACT FROM AUTHOR]

Subacute Sclerosing Panencephalitis (SSPE) is a rare, slowly progressive disorder that affects the entire nervous system. It primarily involves the cerebral cortex, subcortex and optic nerves. Caused by a mutated strain of the measles virus, the disease is mostly irreversible and devastating. It presents with gradually progressive cognitive impairment, extrapyramidal symptoms and sometimes seizures. Although commonly seen in unvaccinated children, SSPE of adult onset is uncommon. The disease is fatal and currently has no treatment. There have been many different presentations of this disorder, ranging from optic nerve involvement to gradual cognitive decline, but none have a good prognosis; ultimately, patients may become akinetic and mute. Here, the authors present an uncommon case of SSPE occurring at an older age (26-year-old male), with a rapid and atypical presentation resembling severe post-viral syndrome, which was later diagnosed as SSPE. [ABSTRACT FROM AUTHOR]

Attenuated measles virus (MV) exerts its oncolytic activity in malignant pleural mesothelioma (MPM) cells that lack type-I interferon (IFN-I) production or responsiveness. However, other cells in the tumor microenvironment (TME), such as myeloid cells, possess functional antiviral pathways. In this study, we aimed to characterize the interplay between MV and the myeloid cells in human MPM. We cocultured MPM cell lines with monocytes or macrophages and infected them with MV. We analyzed the transcriptome of each cell type and studied their secretion and phenotypes by high-dimensional flow cytometry. We also measured transgene expression using an MV encoding GFP (MV-GFP). We show that MPM cells drive the differentiation of monocytes into M2-like macrophages. These macrophages inhibit GFP expression in tumor cells harboring a defect in IFN-I production and a functional signaling downstream of the IFN-I receptor, while having minimal effects on GFP expression in tumor cells with defect of responsiveness to IFN-I. Interestingly, inhibition of the IFN-I signaling by ruxolitinib restores GFP expression in tumor cells. Upon MV infection, cocultured macrophages express antiviral pro-inflammatory genes and induce the expression of IFN-stimulated genes in tumor cells. MV also increases the expression of HLA and costimulatory molecules on macrophages and their phagocytic activity. Finally, MV induces the secretion of inflammatory cytokines, especially IFN-I, and PD-L1 expression in tumor cells and macrophages. These results show that macrophages reduce viral proteins expression in some MPM cell lines through their IFN-I production and generate a pro-inflammatory interplay that may stimulate the patient’s anti-tumor immune response.

Nodding syndrome (NS) is a mostly East African pediatric epileptiform encephalopathy of unknown etiology that shares some clinical features with measles-associated subacute sclerosing panencephalitis (SSPE) and progressive rubella panencephalitis. Two independent studies in northern Uganda identified an association between NS and prior measles infection, while an earlier study in South Sudan found an inverse association. We report preliminary serologic analyses of antibodies to measles (MV), rubella (RV), HSV-1, and CMV viruses in northern Ugandan children with NS and Household (HC) and Community (CC) Controls. Only MV-positive titers were significantly different (3-fold and > 2-fold) in NS relative to HC and HC + CC, respectively. While these results are consistent with greater prior measles infection in Ugandan persons with NS, further studies are needed to determine whether Measles virus (MV) plays any role in the etiology and pathogenesis of NS. Resolving this issue will be invaluable for the thousands of children at risk for this devastating yet often neglected condition.

Macroautophagy/autophagy is a tightly regulated cellular process integral to homeostasis and innate immunity. As such, dysregulation of autophagy is associated with cancer, neurodegenerative disorders, and infectious diseases. While numerous factors that promote autophagy have been characterized, the key mechanisms that prevent excessive autophagy are less well understood. Here, we identify CSNK2/CK2 (casein kinase 2) as a negative regulator of autophagy. Pharmacological inhibition of CSNK2 activity or siRNA-mediated depletion of CSNK2 increased basal autophagic flux in cell lines and primary human lung cells. Vice versa, ectopic expression of CSNK2 reduced autophagic flux. Mechanistically, CSNK2 interacted with the FLN (filamin)-NHL domain-containing tripartite motif (TRIM) family members TRIM2, TRIM3 and TRIM71. Our data show that recruitment of CSNK2 to the C-terminal NHL domain of TRIM3 lead to its robust phosphorylation at serine 661 by CSNK2. A phosphorylation-defective mutant of TRIM3 was unable to reduce autophagosome numbers indicating that phosphorylation by CSNK2 is required for TRIM-mediated autophagy inhibition. All three TRIMs facilitated inactivation of the ULK1-BECN1 autophagy initiation complex by facilitating ULK1 serine 757 phosphorylation. Inhibition of CSNK2 promoted autophagy upon influenza A virus (IAV) and measles virus (MeV) infection. In line with this, targeting of CSNK2 or depletion of TRIM2, TRIM3 or TRIM71 enhanced autophagy-dependent restriction of IAV, MeV and human immunodeficiency virus 1 (HIV-1). Thus, our results identify the CSNK2-TRIM2, -TRIM3, -TRIM71 axis as a key regulatory pathway that limits autophagy. Targeting this axis may allow for therapeutic induction of autophagy against viral infections and in diseases associated with dysregulated autophagy. Abbreviation: ATG5: autophagy related 5; BafA1: bafilomycin A1; BECN1: beclin 1; CCD: coiled-coil domain; CSNK2/CK2: casein kinase 2; CSNK2A1: casein kinase 2 alpha 1; CSNK2A2: casein kinase 2 alpha 2; CSNK2B: casein kinase 2 beta; FLN: filamin; HeLa GL: HeLa cells stably expressing eGFP-LC3B; HIV-1: human immunodeficiency virus 1; IAV: influenza A virus; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3; MeV: measles virus; MTOR: mechanistic target of rapamycin kinase; RING: really interesting new gene; SQSTM1/p62: sequestosome 1; TRIM: tripartite motif; ULK1: unc-51 like autophagy activating kinase 1 [ABSTRACT FROM AUTHOR]

B cell transcriptomic signatures hold promise for the early prediction of vaccineinduced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/PMAIP1, the brain expressed X-linked 2/BEX2 gene and the B cell Fas apoptotic inhibitory molecule/FAIM, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocytederived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination. [ABSTRACT FROM AUTHOR]

The measles vaccine virus strain (MV-Edm) serves as a potential platform for the development of effective oncolytic vectors. Nevertheless, despite promising pre-clinical data, our comprehension of the factors influencing the efficacy of MV-Edm infection and intratumoral spread, as well as the interactions between oncolytic viruses and specific chemotherapeutics associated with viral infection, remains limited. Therefore, we investigated the potency of Forskolin in enhancing the antitumor effect of oncolytic MV-Edm by promoting the Rab27a-dependent vesicular transport system. After infecting cells with MV-Edm, we observed an increased accumulation of cytoplasmic vesicles. Our study demonstrated that MV-Edm infection and spread in tumors, which are indispensable processes for viral oncolysis, depend on the vesicular transport system of tumor cells. Although tumor cells displayed a responsive mechanism to restrain the MV-Edm spread by down-regulating the expression of Rab27a, a key member of the vesicle transport system, over-expression of Rab27a promoted the oncolytic efficacy of MV-Edm towards A549 tumor cells. Additionally, we found that Forskolin, a Rab27a agonist, was capable of promoting the oncolytic effect of MV-Edm in vitro. Our study revealed that the vesicle transporter Rab27a could facilitate the secretion of MV-Edm and the generation of syncytial bodies in MV-Edm infected cells during the MV-Edm-mediated oncolysis pathway. The results of the study demonstrate that a combination of Forskolin and MV-Edm exerts a synergistic anti-tumor effect in vitro, leading to elevated oncolysis. This finding holds promise for the clinical treatment of patients with tumors. [ABSTRACT FROM AUTHOR]

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children and adults, there is an urgent need for a safe and effective vaccine that can elicit systemic and mucosal humoral immunity to limit the emergence of new variants. Using the Chinese Hu191 measles virus (MeV-hu191) vaccine strain as a backbone, we developed MeV chimeras stably expressing the prefusion forms of either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted spike trimers with the help of the SP-D trimerization tag (rMeV-S+SPD) of SARS-CoV-2 Omicron BA.2. The two vaccine candidates were administrated in golden Syrian hamsters through the intranasal or subcutaneous routes to determine the optimal immunization route for challenge. The intranasal delivery of rMeV-S+SPD induced a more robust mucosal IgA antibody response than the subcutaneous route. The mucosal IgA antibody induced by rMeV-preFS through the intranasal routine was slightly higher than the subcutaneous route, but there was no significant difference. The rMeV-preFS vaccine stimulated higher mucosal IgA than the rMeV-S+SPD vaccine through intranasal or subcutaneous administration. In hamsters, intranasal administration of the rMeV-preFS vaccine elicited high levels of NAbs, protecting against the SARS-CoV-2 Omicron BA.2 variant challenge by reducing virus loads and diminishing pathological changes in vaccinated animals. Encouragingly, sera collected from the rMeV-preFS group consistently showed robust and significantly high neutralizing titers against the latest variant XBB.1.16. These data suggest that rMeV-preFS is a highly promising COVID-19 candidate vaccine that has great potential to be developed into bivalent vaccines (MeV/SARS-CoV-2). [ABSTRACT FROM AUTHOR]

We present a 20-year-old woman who was diagnosed with subacute sclerosing panencephalitis (SSPE) 20 months after presenting with unilateral retinitis. At presentation, the patient had two inferotemporal macular lesions in her left eye. Corresponding to these areas, optical coherence tomography (OCT) showed hyporeflective spaces with loss of nearly all of the retinal layers. OCT-angiography (OCTA) demonstrated some flow deficit areas with a reduction in the vessel density. Her serum measles antibody titre was high (IgG >5000.0 mIU/ml). Twenty months later the macular lesions had diminished in size, and there was some focal retinal thinning with interruption of the ellipsoid zone. OCTA showed that the flow deficit areas were diminished in size together with the relatively improved perfusion density. Neurological examination disclosed myoclonic jerks. Neuropsychological assessment demonstrated impaired executive function, attention, and narrowed lexical fluency. Measles IgG antibody was high in the cerebrospinal fluid (>230.0 U/ml). Brain magnetic resonance imaging demonstrated bilateral, non-specific, small foci of T2 hyperintensity in the frontoparietal subcortical white matter and centrum semiovale. The present case is the first where OCTA findings of SSPE-related retinal lesions have been described. [ABSTRACT FROM AUTHOR]

Introduction: Measles is a highly contagious viral disease. In recent years, there has been an alarming increase in measles cases in Europe. Most patients were not vaccinated. The aim of this study was to analyse the clinical manifestation of measles in paediatric patients, considering the differences between infants and older children. Material and methods: This was a retrospective observational study, for which data were collected from the medical records of paediatric patients hospitalised due to measles January 2017 - December 2019. Stratification was based on age. In the younger group (infants), children under 13 months of age were included. Results: In total 84 children were enrolled in the study, including 26 infants (30.95%) and 58 older children (69.5%). In 67/84 (79.76%) participants no history of measles vaccination was reported. Among those not vaccinated, there were 28/67 (41.79%) children too young for vaccination. Fever and erythema occurred in all patients. The disease was complicated by pneumonia in 39/84 (46.43%) and acute otitis media in 19/84 (22.62%) children. Antibiotics were administered in 45/84 (69.05%) cases, of which 10/58 (17.24%) had 2 or more. The infants had significantly less frequent photophobia (p = 0.041693), lymphadenopathy (p = 0.005229), hepatomegaly (p = 0.030619), and splenomegaly (p = 0.019469), Instead, they were significantly more likely to have acute otitis media (p = 0.020141). Conclusions: Measles is a serious disease that most commonly affects unvaccinated children. The most common symptoms include fever and rash. Otitis media and pneumonia were the most common measles complications. The variations in symptoms and complications of measles differ significantly between infants and older children. [ABSTRACT FROM AUTHOR]

Immunological testing to detect neutralizing antibodies (NAbs) is important in measles (MV) infection control. Currently, the plaque reduction neutralization test is the only credible method for measuring actual virus NAbs; however, its feasibility is hampered by drawbacks, such as long turnaround times, low throughput, and the need for laboratory biosafety equipment. To solve these problems, we developed a simple and rapid MV‐NAb detection system using lentivirus‐based virus‐like particles incorporated with the NanoLuc fragment peptide HiBiT comprising the MV fusion protein and hemagglutinin on their exterior surface. Overall, this simple, safe, and rapid method could be used to detect MV NAbs. [ABSTRACT FROM AUTHOR]

Measuring infectious titer is the most time-consuming method during the production and process development of live viruses. Conventionally, it is done by measuring the tissue culture infectious dose (TCID50) or plaque forming units (pfu) in cell-based assays. Such assays require a time span of more than a week to the readout and significantly slow down process development. In this study, we utilized the pro-inflammatory cytokine response of a Vero production cell line to a recombinant measles vaccine virus (MVV) as model system for rapidly determining infectious virus titer within several hours after infection instead of one week. Cytokines are immunostimulatory proteins contributing to the first line of defence against virus infection. The probed cytokines in this study were MCP-1 and RANTES, which are secreted in a virus dose as well as time dependent manner and correlate to TCID50 over a concentration range of several logarithmic levels with R2 = 0.86 and R2 = 0.83, respectively. Furthermore, the pro-inflammatory cytokine response of the cells was specific for infectious virus particles and not evoked with filtered virus seed. We also discovered that individual cytokine candidates may be more suitable for off- or at-line analysis, depending on the secretion profile as well as their sensitivity towards changing process conditions. Furthermore, the method can be applied to follow a purification procedure and is therefore suited for process development and control. • MCP-1 and RANTES are fast surrogate predictors for TCID50. • Infectious virus titer can be measured 18 and 72 hours post infection through pro-inflammatory cytokine response instead of one week. • They can be directly measured during virus production from the bioreactor. • Cytokines correlate with infectious virus over several log TCID50/mL. [ABSTRACT FROM AUTHOR]

Vaccination against measles is one of the most effective public health interventions which has saved millions of lives and interrupted circulation of the natural virus in the population. However, it is widely accepted that the immunity after vaccination can wane, especially in those who have had no contact with the virus. This study aimed to classify the particular birth cohorts of adults with regard to their exposure to the wild measles virus in the population with a long history of mandatory vaccination. We introduced two methods. In the first, we estimated the probability of exposure to the wild virus through an analysis of antibody levels from the Immunologic Survey performed in the Slovak Republic in 2018, while the second was based on historical epidemiological data. Both methods resulted in similar estimations. Cohorts born in Slovakia before 1964 can be considered to be cohorts in which most people were exposed to the wild measles virus. Cohorts born after 1977 can be designated as cohorts that most likely did not come into the contact with the wild virus. Cohorts born between 1965 and 1976 are composed of a mixture, with a decreasing proportion of people exposed to the wild virus with increasing year of birth. The proposed methods can help identify potential immunity gaps in the adult population. They can be applied in other countries with high measles vaccination coverage to estimate the probability of exposure to the wild measles virus in particular birth cohorts. [ABSTRACT FROM AUTHOR]

The measles virus is highly contagious, and efforts to simplify its diagnosis are essential. A reverse transcriptase/recombinase polymerase amplification assay coupled with CRISPR/Cas12a and an immunochromatographic lateral flow detection (RT-RPA-CRISPR-LFD) was developed for the simple visual detection of measles virus. The assay was performed in less than 1 h at an optimal temperature of 42 °C. The detection limit of the assay was 31 copies of an RNA standard in the reaction tube. The diagnostic performances were evaluated on a panel of 27 measles virus RT-PCR-positive samples alongside 29 measles virus negative saliva samples. The sensitivity and specificity were 96% (95% CI, 81–99%) and 100% (95% CI, 88–100%), respectively, corresponding to an accuracy of 98% (95% CI, 94–100%; p < 0.0001). This method will open new perspectives in the development of the point-of-care testing diagnosis of measles. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis is a rare complication due to persistent measles infection, characterized by cognitive and motor deterioration. Because subacute sclerosing panencephalitis is considered a potentially fatal complication of measles and usually presents in young populations, particularly those with measles infection under the age of 2 years, new approaches to implement vaccination programs must be devised to help avoid the worsening of patient outcome. Until the disease is eradicated globally, children in all regions of the world remain at risk of measles infection and its respective complications, and therefore, the vaccine is considered the optimal preventative measure. The legacy of measles virus goes beyond the immediate complications. Our study, therefore, aims to provide a comprehensive review on the updated insights into subacute sclerosing panencephalitis as a complication, as well as the extent and future considerations pertaining to vaccination programs in the pediatric population. [ABSTRACT FROM AUTHOR]

Morbilliviruses are members of the family Paramyxoviridae and are known for their ability to cause systemic disease in a variety of mammalian hosts. The prototypic morbillivirus, measles virus (MeV), infects humans and still causes morbidity and mortality in unvaccinated children and young adults. Experimental infection studies in non-human primates have contributed to the understanding of measles pathogenesis. However, ethical restrictions call for the development of new animal models. Canine distemper virus (CDV) infects a wide range of animals, including ferrets, and its pathogenesis shares many features with measles. However, wild-type CDV infection is almost always lethal, while MeV infection is usually self-limiting. Here, we made five recombinant CDVs, predicted to be attenuated, and compared their pathogenesis to the non-attenuated recombinant CDV in a ferret model. Three viruses were insufficient ly attenuated based on clinical signs, fatality, and systemic infection, while one virus was too attenuated. The last candidate virus caused a self-limiting infection associated with transient viremia and viral dissemination to all lymphoid tissues, was shed transiently from the upper respiratory tract, and did not result in acute neurological signs. Additionally, an in-depth phenotyping of the infected white blood cells showed lower infection percentages in all lymphocyte subsets when compared to the non-attenuated CDV. In conclusion, infection models using this candidate virus mimic measles and can be used to study pathogenesis-related questions and to test interventions for morbilliviruses in a natural host species. [ABSTRACT FROM AUTHOR]

Subacute sclerosing panencephalitis (SSPE) is a rare but fatal late neurological complication of measles, caused by persistent measles virus (MeV) infection of the central nervous system. There are no drugs approved for the treatment of SSPE. Here, we followed the clinical progression of a 5-year-old SSPE patient after treatment with the nucleoside analog remdesivir, conducted a post-mortem evaluation of the patient's brain, and characterized the MeV detected in the brain. The quality of life of the patient transiently improved after the first two courses of remdesivir, but a third course had no further clinical effect, and the patient eventually succumbed to his condition. Post-mortem evaluation of the brain displayed histopathological changes including loss of neurons and demyelination paired with abundant presence of MeV RNA-positive cells throughout the brain. Next-generation sequencing of RNA isolated from the brain revealed a complete MeV genome with mutations that are typically detected in SSPE, characterized by a hypermutated M gene. Additional mutations were detected in the polymerase (L) gene, which were not associated with resistance to remdesivir. Functional characterization showed that mutations in the F gene led to a hyperfusogenic phenotype predominantly mediated by N465I. Additionally, recombinant wild-type-based MeV with the SSPE-F gene or the F gene with the N465I mutation was no longer lymphotropic but instead efficiently disseminated in neural cultures. Altogether, this case encourages further investigation of remdesivir as a potential treatment of SSPE and highlights the necessity to functionally understand SSPE-causing MeV. [ABSTRACT FROM AUTHOR]

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA) +QS-21 adjuvant predominantly induced GC Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 cells with MPLA +QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml- MPLA; 5500; CAF01, 2155; p<0.05). Notably, interferon γ+Env-specific Tfh responses were consistently higher with gp140 in MPLA +QS-21 and positively correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC Tfh1 induction promote persistent Env antibodies, important for protective immunity against HIV. [ABSTRACT FROM AUTHOR]