Search Results (734)

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Artificial intelligence (AI) techniques—ranging from hybrid mechanistic–machine learning (ML) ensembles to gradient-boosted decision trees, support-vector machines, and deep neural networks—are transforming the management of seasonal influenza, respiratory syncytial virus (RSV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptom-based triage models using eXtreme Gradient Boosting (XGBoost) and Random Forests, as well as imaging classifiers built on convolutional neural networks (CNNs), have improved diagnostic accuracy across respiratory infections. Transformer-based architectures and social media surveillance pipelines have enabled real-time monitoring of COVID-19. In HIV research, support-vector machines (SVMs), logistic regression, and deep neural network (DNN) frameworks advance viral-protein classification and drug-resistance mapping, accelerating antiviral and vaccine discovery. Despite these successes, persistent challenges remain—data heterogeneity, limited model interpretability, hallucinations in large language models (LLMs), and infrastructure gaps in low-resource settings. We recommend standardized open-access data pipelines and integration of explainable-AI methodologies to ensure safe, equitable deployment of AI-driven interventions in future viral-outbreak responses. Full article

Human immunodeficiency virus (HIV) infection remains a major challenge in global health. In recent years, vaccines have emerged as an important tool for the treatment and prevention of HIV-related complications. This review article addresses the evolving landscape of vaccines for people living with HIV (PLWH), evaluating current vaccination strategies for standard vaccines and travel vaccines in PLWH compared to the general population and offering a summary of the current recommended vaccines. It evaluates studies for vaccine effectiveness and safety and discusses methods to improve vaccination rates among PLWH. Systematic research was carried out using keywords. We address the current state of knowledge and highlight areas for future research and development. Full article

Background/Objectives: Syphilis, a re-emerging global public health issue, has shown increasing incidence over the past decade, particularly among key populations such as men who have sex with men (MSM), people living with HIV, and pregnant women. This narrative review aimed to synthesize global epidemiological trends of syphilis from 2015 to 2025, with a focus on surveillance gaps, regional disparities, and structural determinants. Methods: A broad narrative approach was used to collect and analyze epidemiological data from 2015 to 2025. The literature was retrieved from databases (PubMed, Scopus) and official reports from the WHO, CDC, and ECDC. Included materials span observational studies, surveillance reports, and modeling data relevant to global trends and public health responses. Results: Globally, syphilis incidence has increased, with notable surges in North America, Europe, and Asia. MSM remain disproportionately affected, while congenital syphilis is resurging even in high-income countries. Low- and middle-income countries report persistent burdens, especially among women of reproductive age, often exacerbated by limited screening and surveillance infrastructure. The COVID-19 pandemic disrupted syphilis-related services and further exacerbated underreporting, hindering timely detection and response efforts. Surveillance systems vary widely in their completeness and quality, which significantly hinders global data comparability and coordinated public health responses. Conclusions: Despite its curability, syphilis continues to spread due to fragmented prevention strategies, inequities in access to care, and insufficient surveillance. Strengthening diagnostic access, integrating prevention efforts into broader health systems, and addressing social determinants are essential. Improved surveillance, equitable access, and innovation—including diagnostics and potential vaccine research—are critical to controlling the global syphilis epidemic. Full article

Objectives: Understanding the antibody response in monkeypox virus (MPXV)-infected and uninfected individuals is essential for developing next-generation MPXV vaccines. This study aimed to characterize neutralizing antibody (NAb) and antibody-dependent cellular cytotoxicity (ADCC) responses in both groups, providing insights into immune protection and vaccine design. Methods: A recombinant vaccinia Tian Tan (VTT) virus was utilized to develop high-throughput luciferase-reporter-based neutralization and ADCC assays. These assays were applied to evaluate the presence and levels of poxvirus-specific antibodies in MPXV-infected and uninfected individuals, including those vaccinated with vaccinia-based vaccines. Results: Poxvirus-specific NAbs were detected in MPXV-negative individuals with prior vaccinia vaccination. However, MSM individuals exhibited significantly lower pre-existing NAb levels than non-MSM individuals, potentially contributing to their higher susceptibility to MPXV infection. In individuals with mild MPXV infection, robust NAb and ADCC responses were observed, regardless of vaccination status. Additionally, HIV-positive individuals demonstrated comparable antibody responses following MPXV infection. Conclusions: These findings highlight the potential role of pre-existing NAbs in MPXV susceptibility and the strong immune response elicited by mild MPXV infection. Further research is needed to determine whether MPXV-specific antibodies mitigate disease progression, which could inform the development of effective MPXV vaccines. Full article

Co-infections of Orthopoxviruses (OPVs), such as vaccinia virus (VACV) and monkeypox virus (MPXV), and the human immunodeficiency virus (HIV) can be associated with severe outcomes. Serro’s dairy region, located in Minas Gerais, southeastern Brazil, is an endemic area for VACV, where zoonotic outbreaks affect rural communities. This epidemiological context is especially relevant for at-risk populations, such as people living with HIV (PLHIV). This study aimed to assess the presence of neutralizing antibodies (NAbs) against OPV in PLHIV in this endemic setting. Serum samples were collected from 177 PLHIV in treatment at the specialized service between December 2021 and August 2022. VACV and MPXV NAbs were measured using the plaque reduction neutralization test (PRNT) and VACV-infected cells. The overall occurrence of OPV NAbs was 27.7%. NAbs were higher in individuals born before 1980 (53.3%) than those born after 1980 (1.1%). Among anti-VACV-seropositive individuals, 40.8% also had MPXV NAbs, suggesting cross-immunity. These findings indicate the circulation of VACV in PLHIV and highlight the increased susceptibility to OPV infections among individuals born after the cessation of smallpox vaccination. The results reinforce the importance of continued surveillance of OPV, especially in endemic regions and vulnerable populations. Full article

Background: Immunological strategies for antibody-guided vaccine design intend to enhance viral neutralization and protection and increase efficacy. Here, we discuss advances in antibody-guided vaccine design and current antibody-guided strategies, including epitope-based, nanoparticle-based, and scaffold-based vaccine approaches. We review the challenges and limitations of vaccines against different pathogens, such as influenza A virus, HIV-1 virus, single-celled malaria parasite, respiratory syncytial virus, and SARS-CoV-2. We summarize the available literature guidance, including emerging techniques in immunological vaccine design, to help understand and improve antibody-based immunity. The search strategy we applied is a comprehensive literature review of major databases, with specific search terms related to antibody-mediated vaccine design, viral neutralization, and immune protection. We discuss the how future directions for next-generation vaccine platforms and personalized vaccines based on immunogenetics will help improve vaccine design for increased specificity and potency of antibodies that neutralize pathogens, offering more precise and effective immune responses and, therefore, protection. Full article

About a quarter of the world’s population is infected with Mycobacterium tuberculosis. Growing antibiotic resistance by this microorganism is a major problem in the therapy of the disease. M. avium-M. intracellulare that emerged as a major opportunistic infection of HIV/AIDS continues to afflict immunocompromised individuals. We describe the use of liposome-encapsulated antibiotics in the experimental and clinical therapy of mycobacterial infections, as well as recent experimental liposomal vaccines against tuberculosis. Liposome-mediated intravenous or inhalational delivery of antibiotics enhances the antibacterial effects of the drugs, particularly for infections of resident macrophages, where the liposomes are passively targeted. Despite experimental successes of liposomal antibiotics in the treatment of mycobacterial and other bacterial infections, applications of this method to the clinic have been lagging. This review underscores the significance of liposomes in the treatment of mycobacterial infections, encompassing their synthesis methods, limitations, and both preclinical and clinical studies, providing guidance for the development of future therapeutic approaches and innovative antimicrobial strategies. Full article

Torquetenovirus (TTV) is a ubiquitous, non-pathogenic DNA virus that has been suggested as a biomarker of immune competence, with the viral load correlating with the level of immunosuppression. However, by detecting non-intact viral particles, standard PCR-based quantification may overestimate the TTV viremia. To improve the clinical relevance of TTV quantification, in this study, we investigated the use of PMAxx™, a virion viability dye that selectively blocks the amplification of compromised virions. Serum samples from 10 Hepatitis C Virus-positive (HCV+) individuals, 81 liver transplant recipients (LTRs), and 40 people with HIV (PWH) were treated with PMAxx™ and analyzed for TTV DNA loads by digital droplet PCR (ddPCR). Furthermore, anti-SARS-CoV-2 IgG levels and neutralizing antibody (nAbs) titers were measured post-COVID-19 vaccination. Using ddPCR, the PMAxx™ treatment significantly reduced the TTV DNA levels in all the groups (mean reduction: 0.66 Log copies/mL), indicating the abundant presence of non-intact, circulating viral genomes. However, correlations between TTV DNA and SARS-CoV-2 IgG or nAbs were weak or absent in both PMAxx™-treated and untreated samples. These findings suggest that while PMAxx™ enhanced the specificity of TTV quantification, it did not improve the predictive value of TTV viremia at assessing vaccine-induced humoral responses. Full article

Virus-like particles (VLPs) have the potential to become a versatile carrier platform for vaccination against multiple diseases. In the light of short process development timelines and the demand for reliable and robust processes, metabolic modeling of cell culture processes offers great advantages when coupled with a Quality-by-Design (QbD) development approach. A previous work was able to demonstrate the accurate prediction of HEK293F PiggyBac cell concentration as well as VLP titer and metabolite production with a reduced metabolic model. This work presents the reduced metabolic model for a more productive cell line Sleeping Beauty and emphasizes the need for model re-parameterization when the producer cell line changes. The goal of precise prediction for a fed-batch and continuous HEK293 cultivation can, therefore, be achieved. In terms of decision-making for downstream unit operations, a soft sensor for the prediction of main impurities like proteins and DNA was introduced for the first time for the production of lentiviral vectors with several terms describing the release of impurities like DNA and proteins, growth-related protein production, and enzymatic degradation activity associated with cell dissociation in an accurate manner. The additional information can contribute to a more efficient design phase by reducing experimental effort as well as during cultivation with data-based decision-making. With the aid of real-time process data acquisition through process analytical technology (PAT), its predictive power can be enhanced and lead to more reliable processes. Full article

In the current global health environment, the spread of the monkeypox virus (MPXV) and the persistent threat of human immunodeficiency virus (HIV) have become critical public health challenges. Since 2022, MPXV has rapidly disseminated worldwide, and nearly half of MPXV-infected individuals are co-infected with HIV. This complex situation calls for innovative preventive strategies. In this study, an innovative multi-epitope vaccine was designed using bioinformatics and immunoinformatic approaches. Ten HIV proteins and nine MPXV proteins were used to predict potential epitopes. Non-allergenic, highly antigenic, IFN-γ-inducible, and non-toxic epitopes were selected to construct the multi-epitope vaccine. It was found that the designed vaccine construct was highly antigenic, soluble, and had acceptable physicochemical properties. Based on molecular docking and molecular dynamics simulation (MDs) analyses, the vaccine construct demonstrated stable and robust interactions with Toll-like receptors (TLR2, TLR3, and TLR4). Although no actual animal experiments have been conducted to evaluate the vaccine’s effectiveness, immune simulations showed that the vaccine could elicit potent humoral and cell-mediated immune responses. Overall, this study provides a promising vaccine candidate against MPXV and HIV co-infection and emphasizes innovative strategies to interrupt the international transmission of these two viruses. Full article

Background: Vaccines represent one of the most affordable and efficient tools for controlling infectious diseases; however, the development of efficacious vaccines against complex pathogens remains a major challenge. Adjuvants play a relevant role in enhancing vaccine-induced immune responses. One such molecule is interferon-stimulated gene 15 (ISG15), a key modulator of antiviral immunity that acts both through ISGylation-dependent mechanisms and as a cytokine-like molecule. Methods: In this study, we assessed the immunostimulatory potential of ISG15 as an adjuvant in Modified Vaccinia virus Ankara (MVA)-based vaccine candidates targeting Zika virus (ZIKV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Early innate responses and immune cell infiltration were analyzed in immunized mice by flow cytometry and cytokine profiling. To elucidate the underlying mechanism of action of ISG15, in vitro co-infection studies were performed in macrophages. Finally, we evaluated the magnitude and functional quality of the elicited antigen-specific cellular immune responses in vivo. Results: Analysis of early innate responses revealed both platform- and variant-specific effects. ISG15AA preferentially promoted natural killer (NK) cell recruitment at the injection site, whereas ISG15GG enhanced myeloid cell infiltration in draining lymph nodes (DLNs), particularly when delivered via MVA. Moreover, in vitro co-infection of macrophages with MVA-based vaccine vectors and the ISG15AA mutant led to a marked increase in proinflammatory cytokine production, highlighting a dominant role for the extracellular, ISGylation-independent functions of ISG15 in shaping vaccine-induced immunity. Notably, co-infection of ISG15 with MVA-ZIKV and MVA-SARS-CoV-2 vaccine candidates enhanced the magnitude of antigen-specific immune responses in both vaccine models. Conclusions: ISG15, particularly in its ISGylation-deficient form, acts as a promising immunomodulatory adjuvant for viral vaccines, enhancing both innate and adaptive immune responses. Consistent with previous findings in the context of Human Immunodeficiency virus type 1 (HIV-1) vaccines, this study further supports the potential of ISG15 as an effective adjuvant for vaccines targeting viral infections such as ZIKV and SARS-CoV-2. Full article

Background: Human immunodeficiency virus (HIV) remains a global health challenge despite significant advancements in antiretroviral therapy and prevention strategies. Developing a safe and effective vaccine that protects people worldwide has been a major goal, yet the genetic variability and rapid mutation rate of the virus continue to pose substantial challenges. Methods: In this review paper, we aim to provide a comprehensive review of previous vaccine candidates and the progress made in HIV vaccine clinical trials, spanning from the late 1990s to 2025. PubMed and ClinicalTrials.gov were searched for English-language Phase 1–3 HIV vaccine trials published from 1990 to March 2025. After de-duplication, titles/abstracts and then full texts were screened; trial phase, regimen, immunogenicity, efficacy, and correlates were extracted into a structured spreadsheet. Owing to platform heterogeneity, findings were synthesized narratively and arranged chronologically to trace the evolution of vaccine strategies. Results: Early vaccine trials demonstrated that a protein subunit vaccine failed to protect against infection, revealing the complexity of HIV evasion strategies and shifting the focus to a comprehensive immune response, including both antibody and T-cell responses. Trials evaluating the role of viral vectors in generating cell-mediated immunity were also insufficient, and suggested that targeting T cell response alone was not enough. In 2009, the RV144 trial made a breakthrough by showing partial protection against HIV infection and providing the first indication of efficacy. This partial success influenced subsequent trials, prompting researchers to further explore the complex immune response required for protection and consider combinations of vaccine technologies to achieve robust, long-lasting immunity. Conclusion: Despite setbacks, decades of rigorous efforts have provided significant contributions to HIV vaccine discovery and development, offering hope for preventing and protecting against HIV infection. The field remains active by continuing to advance our understanding of the virus, refining vaccine strategies, and employing novel technologies. Full article

Background/Objectives: In addition to classical transmission routes, hepatitis A (HA) outbreaks were, for the first time, linked to sexual activity in the late 1970s, particularly among men who have sex with men (MSM). Since then, outbreaks have continued to emerge globally among adults engaging in high-risk sexual behaviors, reinforcing the ongoing public health significance of this transmission route. Although the COVID-19 pandemic temporarily reduced HA cases, outbreaks reemerged following the relaxation of pandemic measures. This study aims to report the HA outbreak registered at Romania’s tertiary infectious diseases hospital during the first half of 2022. Methods: We retrospectively analyzed all HA cases admitted to the National Institute for Infectious Diseases from 1 January to 1 August 2022. Results: Among 51 cases, eight children (under 14) were excluded from further analyses. Of the 43 remaining cases, 37 (86%) were male, with 20/37 (54.05%) identified as MSM. Twenty-two of the males (59.45%) were previously or concomitantly diagnosed with sexually transmitted diseases (STDs), notably syphilis and HIV. A marginal finding: 14 out of 29 patients screened for hepatitis E tested positive for IgM. The MSM patients exhibited significantly higher transaminase levels (ALT median level 3404 U/L [IQR 2608–5448] vs. 2066 U/L [IQR 1393–3682]) and more severe liver impairment (INR median level 1.37 [IQR 1.18–1.78] vs. 1.18 [IQR 1.11–1.43] compared to non-MSM patients. While direct bilirubin levels were higher in MSM (7.4 mg/dL vs. 5.5 mg/dL), the difference was not statistically significant. Conclusions: An HA outbreak occurred at the beginning of 2022 among Romanian young MSM, with a more severe acute liver injury. High-risk sexual practices may be a potential risk factor for severe HA. This emphasizes the need to screen for STDs in young males with HA and review vaccination policies for at-risk individuals. Full article