Search Results (2,700)

Antigenicity and immunogenicity define a potent immunogen in vaccinology. Nowadays, there are simplified platforms to produce nanocarriers for small-peptide antigen delivery, derived from various infectious agents for the treatment of a variety of diseases, based on virus-like particles (VLPs). They have good cell-penetrating properties and protective action for target molecules from degradation. Human papillomavirus (HPV) causes anogenital warts and six types of cancer in infected women, men, or children, posing a challenge to global public health. The HPV capsid is composed of viral type-specific L1 and evolutionarily conserved L2 proteins. Produced in heterologous systems, the L1 protein can self-assemble into VLPs, nanoparticles sized around 50–60 nm, used as prophylactic vaccines. Devoid of the viral genome, they are safe for users, offering no risk of infection because VLPs do not replicate. The immune response induced by HPV VLPs is promoted by conformational viral epitopes, generating effective T- and B-cell responses. Produced in different cell systems, HPV16 L1 VLPs can be obtained on a large scale for use in mass immunization programs, which are well established nowadays. The expression of heterologous proteins was evaluated at various transfection times by transfecting cells with vectors encoding codon-optimized HPV16L1 and HPV16L2 genes. Immunological response induced by chimeric HPV16 L1/L2 VLP was evaluated through preclinical assays by antibody production, suggesting the potential of broad-spectrum protection against HPV as a prophylactic nanovaccine. These platforms can also offer promising therapeutic strategies, covering the various possibilities for complementary studies to develop potential preventive and therapeutic vaccines with broad-spectrum protection, using in silico new epitope selection and innovative nanotechnologies to obtain more effective immunobiologicals in combating HPV-associated cancers, influenza, hepatitis B and C, tuberculosis, human immunodeficiency virus (HIV), and many other illnesses. Full article

Monkeypox (Mpox), a re-emerging zoonotic disease, has garnered global attention due to its evolving epidemiology, diverse clinical manifestations, and significant public health impact. The rapid international spread of the Mpox prompted the World Health Organization to designate the outbreak as a Public Health Emergency of International Concern. Accurate and timely diagnosis is hindered by its critical resemblance to other orthopoxviruses and viral exanthems, underscoring the need for improved diagnostic tools. Point-of-care diagnostic innovations, including CRISPR-based and smartphone-integrated technologies, have revolutionized outbreak management, offering rapid and accurate detection critical for containment and treatment. The effective control of Mpox outbreak underscores the necessity of strengthened global surveillance, equitable healthcare access, rapid diagnostics, the prompt isolation of infected individuals, and the implantation of ring vaccination strategies. The integration of a “One Health” framework that links human, animal, and environmental health is vital for sustained preparedness. Advances in vaccine development, including novel bionic self-adjuvating vaccines and platforms utilizing DNA, mRNA, and viral vectors, highlight promising prevention efforts. However, issues such as vaccine hesitancy, limited immunization coverage and accessibility in resource-constrained regions remain significant barriers. Therapeutic interventions like tecovirimat and the JYNNEOS vaccine demonstrate efficacy but face challenges in scalability and deployment. To address these multifaceted challenges, this review delves into the molecular insights, clinical features, epidemiological trends, and diagnostic challenges posed by Mpox. This review further highlights the critical need for robust scientific evidence and sustained research to inform effective, evidence-based responses, and long-term management strategies for Mpox outbreaks. Full article

Surface-enhanced Raman scattering (SERS) has emerged as a powerful signal amplification strategy to address the inherent limitations of conventional flow-based diagnostic methods such as lateral flow analysis (LFA) and vertical flow analysis (VFA). By incorporating SERS-active nanostructures into these platforms, SERS-integrated LFA and VFA systems have significantly improved sensitivity, specificity, and multiplexing performance while maintaining the simplicity and portability of conventional approaches. In this review, we summarize recent advances in SERS-enhanced flow-based diagnostics with a focus on exogenous and endogenous disease detection. Exogenous targets include viral antigens, bacterial pathogens, and foodborne contaminants such as mycotoxins and antibiotic residues. Endogenous applications include therapeutic drug monitoring, inflammation profiling, cancer biomarker detection, and exosome-based molecular subtyping. We highlight the structural differences between LFA and VFA approaches and their impact on analytical performance, and explore the advantages of SERS-integrated platforms for rapid and multiplexed detection in complex biological matrices. Finally, we provide an overview of key technical challenges, such as signal reproducibility, matrix interference, and device integration, and discuss future directions for clinical implementation of SERS-based flow diagnostics in point-of-care settings. Full article

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with cure rates exceeding 80% due to advancements in treatment protocols and supportive care. However, in children with Down syndrome (DS), ALL (DS-ALL) presents distinct genomic and clinical challenges. These include mutations in Janus kinase 2 (JAK2), neuroblastoma RAS viral oncogene homolog (NRAS), and E1A-binding protein p300 (EP300), as well as cytokine receptor-like factor 2 (CRLF2) rearrangements—such as P2RY8-CRLF2 fusion—and intrachromosomal amplification of chromosome 21 (iAMP21). These aberrations are associated with poor prognosis and increased risk of relapse. The objective of this study was to present a unique DS-ALL case with five concurrent high-risk genomic lesions and to contextualize its management in light of existing literature, emphasizing minimal residual disease (MRD)-guided therapy and supportive care. Case Report and Results: We present the case of a three-year-old boy with DS and B-cell ALL (B-ALL), in whom multiple high-risk genomic features co-occurred. Despite these adverse prognostic markers, the patient achieved complete remission following an intensive high-dose induction protocol. We also discuss therapeutic strategies that aim at balancing individualized treatment approaches with optimized supportive care to reduce toxicity and minimize relapse risk. Conclusions: This case underlines the importance of comprehensive molecular diagnostics, serial MRD monitoring, and personalized multidisciplinary care in DS-ALL. Full article

Viruses have evolved sophisticated solutions to evade host immunity. One of the most pervasive strategies is molecular mimicry, whereby viruses imitate the molecular and biophysical features of their hosts. This mimicry poses significant challenges for immune recognition, therapeutic targeting, and vaccine development. In this study, we leverage pretrained protein language models (PLMs) to distinguish between viral and human proteins. Our model enables the identification and interpretation of viral proteins that most frequently elude classification. We characterize these by integrating PLMs with explainable models. Our approach achieves state-of-the-art performance with ROC-AUC of 99.7%. The 3.9% of misclassified sequences are signified by viral proteins with low immunogenicity. These errors disproportionately involve human-specific viral families associated with chronic infections and immune evasion, suggesting that both the immune system and machine learning models are confounded by overlapping biophysical signals. By coupling PLMs with explainable AI techniques, our work advances computational virology and offers mechanistic insights into viral immune escape. These findings carry implications for the rational design of vaccines, and improved strategies to counteract viral persistence and pathogenicity. Full article

The 2022 global mpox outbreak, caused by clade IIb of the monkeypox virus (MPXV), prompted emergency use authorisation of the Modified Vaccinia Ankara–Bavarian Nordic (MVA-BN) vaccine, previously approved for smallpox prevention. Understanding immune responses to the MVA-BN vaccine is critical to inform both current and future mpox vaccine policy, particularly amid reports of breakthrough infections in vaccinated persons, uncertainty about the durability of vaccine-induced protection, and the emergence of further outbreaks of mpox from different viral clades, including the clade I-driven public health emergency of international concern. MVA-BN elicits binding and neutralising antibody, memory B cells, and T cell responses. Immune responses vary by host factors, prior orthopoxvirus exposure, and dosing regimens. While seroconversion is generally robust, circulating antibody titres often wane rapidly, particularly in vaccinia-naïve and/or immunocompromised individuals, including people with HIV. Vaccine-induced neutralising antibody responses to MPXV are frequently lower than to vaccinia virus, and their role in protection remains ill-defined. In contrast, T cell responses appear more sustained and may support long-term immunity in the absence of persistent antibody titres. This narrative review synthesises current evidence on the immunogenicity and durability of MVA-BN vaccination, highlights challenges in assay interpretation, and outlines key research priorities, including the need to explore correlates of protection, booster strategies, and next-generation vaccine design. Full article

Monkeypox virus (MPXV) experienced an unprecedented global outbreak in 2022, characterized by a significant departure from historical patterns: a rapid spread of the epidemic to more than 110 non-traditional endemic countries, with more than 90,000 confirmed cases; a fundamental shift in the mode of transmission, with human-to-human transmission (especially among men who have sex with men (MSM)) becoming the dominant route (95.2%); and genetic sequencing revealing a key adaptive mutation in a novel evolutionary branch (Clade IIb) that triggered the outbreak. These features highlight the significant evolution of MPXV in terms of host adaptation, transmission efficiency, and immune escape ability. The aim of this paper is to provide insights into the viral adaptive evolutionary mechanisms driving this global outbreak, with a particular focus on the role of immune escape (e.g., novel mechanisms of M2 proteins targeting the T cell co-stimulatory pathway) in enhancing viral transmission and pathogenicity. At the same time, we systematically evaluate the cross-protective efficacy and limitations of existing vaccines (ACAM2000, JYNNEOS, and LC16), as well as recent advances in novel vaccine platforms, especially mRNA vaccines, in inducing superior immune responses. The study further reveals the constraints to outbreak control posed by grossly unequal global vaccine distribution (e.g., less than 10% coverage in high-burden regions such as Africa) and explores the urgency of optimizing stratified vaccination strategies and facilitating technology transfer to promote equitable access. The core of this paper is to elucidate the dynamic game between viral evolution and prevention and control strategies (especially vaccines). The key to addressing the long-term epidemiological challenges of MPXV in the future lies in continuously strengthening global surveillance of viral evolution (early warning of highly transmissible/pathogenic variants), accelerating the development of next-generation vaccines based on new mechanisms and platforms (e.g., multivalent mRNAs), and resolving the vaccine accessibility gap through global collaboration to build an integrated defense system of “Surveillance, Research and Development, and Equitable Vaccination,” through global collaboration to address the vaccine accessibility gap. Full article

Authorized SARS-CoV-2 vaccines elicit both antibody and T-cell responses; however, benchmark correlates and update decisions have largely emphasized neutralizing antibodies. Motivated by the complementary role of cellular immunity, we designed a prototype polyepitope DNA vaccine encoding conserved human and mouse T-cell epitopes from non-structural proteins of the original strain SARS-CoV-2 lineage. Epitope selection was guided by in silico predictions for common HLA class I alleles in the Brazilian population and the mouse H-2Kb haplotype. To enhance immunogenicity, the polyepitope sequences were fused to glycoprotein D (gD) from Herpes Simplex Virus 1 (HSV-1), an immune activator of dendritic cells (DCs), leading to enhanced activation of antigen-specific T-cell responses. Mice were immunized with two doses of the electroporated DNA vaccine encoding the gD-fused polyepitope, which induced robust interferon-gamma– and tumor necrosis factor-alpha–producing T cell responses compared to control mice. In addition, K18-hACE2 transgenic mice showed protection against intranasal challenge with the original SARS-CoV-2 strain, with reduced clinical symptoms, less weight loss, and decreased viral burden in both lung and brain tissues. The results experimentally confirm the protective role of T cells in vaccine-induced protection against SARS-CoV-2 and open perspectives for the development of universal anti-coronavirus vaccines. Full article

Cervical cancer remains a significant public health challenge, disproportionately affecting women in low- and middle-income countries (LMICs). Persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16 and HPV18, is the central cause of cervical carcinogenesis, driven by the viral oncoproteins E6 and E7, which disrupt the host tumor suppressors p53 and retinoblastoma protein (pRb). Advances in molecular understanding have catalyzed effective primary and secondary prevention strategies. Prophylactic HPV vaccination, especially the nonavalent formulation, has demonstrated high efficacy in reducing HPV infections and cervical precancer. Concurrently, HPV deoxyribonucleic acid (DNA) testing, self-sampling, and screen-and-treat protocols are transforming screening paradigms, particularly in resource-limited settings. However, global disparities in vaccine access, screening coverage, and health infrastructure persist, impeding progress toward the World Health Organization’s (WHO) 90–70–90 elimination targets. By synthesizing recent advances in virology, prevention strategies, and implementation innovations, such as therapeutic vaccines, artificial-intelligence (AI)-driven diagnostics, and mobile health solutions, this review sheds light on their potential to narrow these equity gaps. Full article

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment. Full article

Influenza virus is a leading cause of global morbidity and mortality due to acute lower respiratory infection, even with the widespread use of multiple licensed influenza vaccines. However, antigenic drift during influenza replication can cause vaccine-induced antibodies to poorly neutralize influenza virus, thereby reducing vaccine effectiveness. To help overcome this problem, we leveraged a hydrogel platform with influenza hemagglutinin (HA) protein to induce prolonged antigen exposure. The hydrogel platform, Vaccine Self-Assembling Immune Matrix (VacSIM^®), in combination with recombinant influenza H1 or H3 HA protein antigens, increased antigen-specific antibody titers in vaccinated mice, which led to decreased disease severity after H1N1 infection for H1 HA-vaccinated mice and decreased lung viral titers after H3N2 challenge for H3 HA-vaccinated mice. Sera collected from mice immunized with VacSIM and HA also showed broader HAI activity, increasing by 1–3 log against a panel of influenza viruses. These results were consistent with the use of cocktail immunization, containing both an H1 and H3 HA, where mice immunized with VacSIM had an increase in antigen-specific antibody titers and decreased disease severity and lung viral titers against H1N1 and H3N2 influenza challenges, respectively. Finally, it was determined that a single immunization with VacSIM and H1 HA could provide protection against lethal H1N1 challenge compared to a group without VacSIM. In summary, we demonstrate that use of the slow-release platform VacSIM can improve the host immune response to vaccination and increase protection against influenza infection. Full article

RNA virus populations exist as quasispecies-complex, dynamic clouds of closely related but genetically diverse variants generated by high mutation rates during replication. Assessing quasispecies structure and diversity is crucial for understanding viral evolution, adaptation, and response to antiviral treatments. However, comparing single quasispecies observations from individual biosamples, especially at different infection or treatment time points, presents statistical challenges. Traditional inferential tests are inapplicable due to the lack of replicate observations, and resampling-based approaches such as the bootstrap and jackknife are limited by biases and non-independence, particularly for diversity indices sensitive to rare haplotypes. In this study, we address these limitations by applying the delta method to derive analytical variances for a set of quasispecies structure indicators specifically designed to assess the quasispecies maturation state. We demonstrate the utility of this approach using high-depth next-generation sequencing data from hepatitis C virus (HCV) quasispecies evolving in vitro under various conditions, including free evolution and exposure to antiviral or mutagenic treatments. Our results reveal that with highly fit HCV quasispecies, sofosbuvir inhibits quasispecies genetic diversity, while mutagenic treatments accelerate maturation, compared to untreated controls. We emphasize the interpretation of results through absolute differences, log-fold changes, and standardized effect sizes, moving beyond mere statistical significance. This framework enables robust, quantitative comparisons of quasispecies diversity from single observations, providing valuable insights into viral adaptation and treatment response. The R code and session info with required libraries and versions is provided in the supplementary material. Full article

Enteroviruses, a diverse genus within the Picornaviridae family, are responsible for a wide range of human infections, including hand, foot, and mouth disease, respiratory disease, aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis. Despite their substantial global health burden and the frequent emergence of outbreaks, no specific antiviral therapies are currently approved for clinical use against non-polio enteroviruses. This review provides a comprehensive overview of the current landscape of antiviral strategies targeting enteroviruses, including direct-acting antivirals such as capsid binders, protease inhibitors, and viral RNA polymerase inhibitors. We also examine the potential of host-targeting agents that interfere with virus–host interactions essential for replication. Emerging strategies such as immunotherapeutic approaches, RNA interference, CRISPR-based antivirals, and peptide-based antivirals are also explored. Furthermore, we address key challenges, including viral diversity, drug resistance, and limitations in preclinical models. By highlighting recent advances and ongoing efforts in antiviral development, this review aims to guide future research and accelerate the discovery of effective therapies against enterovirus infections. Full article

Sindbis virus (SINV), a prototype of the Alphavirus genus (family Togaviridae), is a globally distributed arbovirus causing febrile rash and debilitating arthritis in humans. Viral structural proteins—capsid (C), E1, and E2—are fundamental to the virion’s architecture, mediating all stages from assembly to host cell entry and pathogenesis, thus representing critical targets for study. This review consolidates the historical and current understanding of SINV structural biology, tracing progress from early microscopy to recent high-resolution cryo-electron microscopy (cryo-EM) and X-ray crystallography. We detail the virion’s precise T = 4 icosahedral architecture, composed of a nucleocapsid core and an outer glycoprotein shell. Key functional roles tied to protein structure are examined: the capsid’s dual capacity as a serine protease and an RNA-packaging scaffold that interacts with the E2 cytoplasmic tail; the E1 glycoprotein’s function as a class II fusion protein driving membrane fusion; and the E2 glycoprotein’s primary role in receptor binding, which dictates cellular tropism and serves as the main antigenic target. Furthermore, we connect these molecular structures to viral evolution and disease, analyzing how genetic variation among SINV genotypes, particularly in the E2 gene, influences host adaptation, immune evasion, and the clinical expression of arthritogenic and neurovirulent disease. In conclusion, the wealth of structural data on SINV offers a powerful paradigm for understanding alphavirus biology. However, critical gaps persist, including the high-resolution visualization of dynamic conformational states during viral entry and the specific molecular determinants of chronic disease. Addressing these challenges through integrative structural and functional studies is paramount. Such knowledge will be indispensable for the rational design of next-generation antiviral therapies and broadly protective vaccines against the ongoing threat posed by SINV and related pathogenic alphaviruses. Full article

Background: Differentiating between bacterial and viral infections in pediatric emergency care is challenging, often leading to unnecessary antibiotic use. The MeMed BV (MMBV) test is a host-response assay designed to differentiate bacterial from viral infections, but real-world data in pediatric settings remain limited. Methods: We conducted a pragmatic, single-center, prospective cohort study to assess the clinical utility of MMBV in children with acute respiratory infections or fever without source. Patients were assigned to standard of care (SOC) or MMBV testing (SOC+MMBV) based on time of presentation to the emergency department. The primary outcome was antibiotic prescribing. Secondary outcomes included diagnostic test utilization, hospitalization rates, and length of stay. Analyses were stratified by hospitalization status, clinical severity [National Institute for Health and Care Excellence (NICE) traffic light system], and patient age. Results: From July 2023 to April 2024, 343 patients were enrolled (171 SOC, 172 SOC+MMBV). In the SOC+MMBV arm, reduced antibiotic prescribing was observed among outpatients and those with non-severe signs and symptoms. Antibiotic prescribing was significantly reduced in children under five years with a low-risk profile, according to the NICE traffic light system (26.3% vs. 7.5%; p = 0.034). Multiplex PCR testing was significantly reduced in the SOC+MMBV group (28.7% vs. 16.3%; p = 0.006) compared to SOC for both inpatients and outpatients. No significant differences were observed in overall diagnostic test use or length of stay. Conclusions: MMBV improved antibiotic and diagnostic stewardship in a real-world pediatric ED setting, significantly reducing unnecessary antibiotic use among low-risk children under five and minimizing unnecessary multiplex PCR testing across the cohort. Full article