Search Results (553)

Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating vaccine-induced immunity, including enhancement of mucosal IgA production, CD8⁺ T-cell activation, and modulation of systemic immune responses. Engineered commensal bacteria such as Lactococcus lactis, Bacteroides ovatus, Bacillus subtilis, and Staphylococcus epidermidis have emerged as promising live vectors for antigen delivery. Postbiotic and synbiotic strategies further enhance protective efficacy through targeted modulation of the gut microbiota. Additionally, artificial intelligence (AI)-driven tools enable predictive modeling of host–microbiome interactions, antigen design optimization, and early detection of viral antigenic drift. These integrative technologies offer a new framework for mucosal, broadly protective, and field-deployable vaccines for HPAI control. However, species-specific microbiome variation, ecological safety concerns, and scalable manufacturing remain critical challenges. This review synthesizes emerging evidence on microbiome–immune crosstalk, commensal vector platforms, and AI-enhanced vaccine development, emphasizing the urgent need for One Health integration to mitigate zoonotic adaptation and pandemic emergence. Full article

Circular RNAs (circRNAs) have emerged as a transformative class of RNA therapeutics, distinguished by their closed-loop structure conferring nuclease resistance, reduced immunogenicity, and sustained translational activity. While challenges in pharmacokinetic control and manufacturing standardization require resolution, emerging synergies between computational design tools and modular delivery platforms are accelerating clinical translation. In this review, we synthesize recent advances in circRNA therapeutics, with a focused analysis of their stability and immunogenic properties in vaccine and drug development. Notably, key synthesis strategies, delivery platforms, and AI-driven optimization methods enabling scalable production are discussed. Moreover, we summarize preclinical and emerging clinical studies that underscore the potential of circRNA in vaccine development and protein replacement therapies. As both a promising expression vehicle and programmable regulatory molecule, circRNA represents a versatile platform poised to advance next-generation biologics and precision medicine. Full article

One concern in the yearly re-formulation of influenza vaccines is the time-consuming manufacturing of vaccine potency reagents, particularly for emergency responses. The continuous evaluation of modern techniques such as reversed-phase (RP) chromatography is an asset for streamlining this process. One challenge with RP methods, however, is the need to re-optimize methods for antigens that show poor separation, which can be highly dependent on analyst experience and available data. In this study, we leveraged a large RP dataset of influenza antigens to explore machine learning (ML) approaches of classifying challenging separations for computer-assisted method re-optimization across years, products, and analysts. Methods: To address recurring chromatographic issues—such as poor resolution, strain co-elution, and signal absence—we applied data augmentation techniques to correct class imbalance and trained multiple supervised ML classifiers to distinguish between these peak profiles. Results: With data augmentation, several ML models demonstrated promising accuracy in classifying chromatographic profiles according to the provided labels. These models effectively distinguished patterns indicative of separation issues in real-world data. Conclusions Our findings highlight the potential of ML as a computer assisted tool in the evaluation of vaccine quality, offering a scalable and objective approach to chromatogram classification. By reducing reliance on manual interpretation, ML can expedite the optimization of analytical methods, which is particularly needed for rapid responses. Future research involving larger, inter-laboratory datasets will further elucidate the utility of ML in vaccine analysis. Full article

The convergence of artificial intelligence (AI) and nanomedicine has transformed cancer vaccine development, particularly in optimizing RNA-loaded lipid nanoparticles (LNPs). Stability and targeted delivery are major obstacles to the clinical translation of promising RNA-LNP vaccines for cancer immunotherapy. This systematic review analyzes the AI’s impact on LNP engineering through machine learning-driven predictive models, generative adversarial networks (GANs) for novel lipid design, and neural network-enhanced biodistribution prediction. AI reduces the therapeutic development timeline through accelerated virtual screening of millions of lipid combinations, compared to conventional high-throughput screening. Furthermore, AI-optimized LNPs demonstrate improved tumor targeting. GAN-generated lipids show structural novelty while maintaining higher encapsulation efficiency; graph neural networks predict RNA-LNP binding affinity with high accuracy vs. experimental data; digital twins reduce lyophilization optimization from years to months; and federated learning models enable multi-institutional data sharing. We propose a framework to address key technical challenges: training data quality (min. 15,000 lipid structures), model interpretability (SHAP > 0.65), and regulatory compliance (21CFR Part 11). AI integration reduces manufacturing costs and makes personalized cancer vaccine affordable. Future directions need to prioritize quantum machine learning for stability prediction and edge computing for real-time formulation modifications. Full article

Vaccine equity and access remain critical challenges in global health, particularly in regions with complex socio-political landscapes, like the Middle East. This review examines disparities in vaccine distribution within the Middle Eastern context, analyzing the unique challenges and opportunities across the region. It provides an overview of the area’s diverse finances and its impact on healthcare accessibility. We examine vaccination rates and identify critical barriers to vaccination, which may be particular issues in developing countries, such as vaccine thermostability, logistical hurdles, financial constraints, and socio-cultural factors, or broader problems, like political instability, economic limitations, and deficiencies in healthcare infrastructure. However, we also highlight successful efforts at the regional and national levels to improve vaccine equity, along with their outcomes and impacts. Ultimately, by drawing on the experiences of previous programs and initiatives, we propose strategies to bridge the gaps in vaccine access through sustainable financing, local manufacturing, and the strengthening of health systems. This approach emphasizes the importance of regional collaboration and long-term self-sufficiency in enhancing global health security and achieving more equitable outcomes in the Middle East. Full article

Background/Objectives: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but—due to limited breadth of the immune response—they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. Methods: Specifically, four proprietary adjuvants (EmT4^TM, LiT4Q^TM, MiT4^TM, and AlT4^TM) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. Results: Results showed significant improvement in immune response strength and breadth—especially against more distant SARS-CoV-2 variants such as Omicron—when adjuvants were used in combination with boosters following an RNA vaccine prime. Conclusions: The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity. Full article

Rapid vaccine availability is essential for effective epidemic and pandemic response. Building on the Coalition for Epidemic Preparedness Innovations (CEPI) 100 Days Mission, which aims to have new vaccines ready for initial authorization and manufacturing at scale within 100 days of recognition of a pandemic pathogen, the CEPI has developed a Chemistry, Manufacturing and Controls (CMC) Rapid Response Framework to define technical and logistical CMC requirements to enable rapid vaccine availability. Central to this framework is the availability of adaptable vaccine platforms that can be readily tailored to emerging pathogens. To support strategic decision-making and identify gaps in platform capabilities, CEPI has created the Platform Readiness Dashboard. This tool provides a structured, multi-dimensional initial assessment of platform maturity across six key categories: Adaptability, Compatibility, Suitability, Regulatory, Manufacturing, and Facility Readiness. Each category includes specific technical and operational considerations scored using a color-coded system to reflect outbreak response readiness level. This Dashboard aims to enable vaccine developers, manufacturers, funders, and outbreak response teams to evaluate platform strengths and limitations at any given time, informing funding, preparedness and response activities. By offering a dynamic view of essential platform readiness indicators, the dashboard can communicate progress supporting faster responses to future health emergencies. Full article

The 100-Day Mission, coordinated by the Coalition for Epidemic Preparedness Innovations (CEPI) and endorsed by significant international stakeholders, aims to shorten the timeframe for developing and implementing vaccines to 100 days after the report of a new pathogen. This ambitious goal is outlined as an essential first step in improving pandemic preparedness worldwide. This review highlights the mission’s implementation potential and challenges by examining it through the lens of low- and middle-income countries (LMICs), which often face barriers to equitable vaccine access. This article explores the scientific, economic, political, and social aspects that could influence the mission’s success, relying on lessons learned from previous pandemics, such as the Spanish flu, H1N1, and COVID-19. We also examined important cornerstones like prototype vaccine libraries, accelerated clinical trial preparedness, early biomarkers identification, scalable manufacturing capabilities, and rapid pathogen characterization. The review also explores the World Health Organization (WHO) Pandemic Agreement and the significance of Phase 4 surveillance in ensuring vaccine safety. We additionally evaluate societal issues that disproportionately impact LMICs, like vaccine reluctance, health literacy gaps, and digital access limitations. Without intentional attempts to incorporate under-resourced regions into global preparedness frameworks, we argue that the 100-Day Mission carries the risk of exacerbating already-existing disparities. Ultimately, our analysis emphasizes that success will not only rely on a scientific innovation but also on sustained international collaboration, transparent governance, and equitable funding that prioritizes inclusion from the beginning. Full article

Background/Objectives: Beak and feather disease virus (BFDV) is the causative agent of psittacine beak and feather disease (PBFD), affecting psittacine birds. There is currently no commercial vaccine or treatment for this disease. This study developed a novel BFDV coat protein mRNA vaccine encapsidated by TMV coat protein to form pseudovirions (PsVs) and tested its immunogenicity alongside BFDV coat protein (CP) subunit and DNA vaccine candidates. Methods: mRNA and BFDV CP subunit vaccine candidates were produced in Nicotiana benthamiana and subsequently purified using PEG precipitation and gradient ultracentrifugation, respectively. The DNA vaccine candidate was produced in E. coli cells harbouring a plasmid with a BFDV1.1mer pseudogenome. Immunogenicity of the vaccine candidates was evaluated in African grey parrot chicks. Results: Successful purification of TMV PsVs harbouring the mRNA vaccine, and of the BFDV-CP subunit vaccine, was confirmed by SDS-PAGE and western blot analysis. TEM analyses confirmed formation of TMV PsVs, while RT-PCR and RT-qPCR cDNA amplification confirmed encapsidation of the mRNA vaccine candidate within TMV particles. Restriction digests verified presence of the BFDV1.1mer genome in the plasmid. Four groups of 5 ten-week-old African grey parrot (Psittacus erithacus) chicks were vaccinated and received two boost vaccinations 2 weeks apart. Blood samples were collected from all four groups on day 14, 28 and 42, and sera were analysed using indirect ELISA, which showed that all vaccine candidates successfully elicited specific anti-BFDV-CP immune responses. The subunit vaccine candidate showed the strongest immune response, indicated by higher binding titres (>6400), followed by the mRNA and DNA vaccine candidates. Conclusions: The candidate vaccines present an important milestone in the search for a protective vaccine against PBFD, and their inexpensive manufacture could considerably aid commercial vaccine development. Full article

CRISPR technology, which is derived from the bacterial adaptive immune system, has transformed traditional genetic engineering techniques, made strain engineering significantly easier, and become a very versatile genome editing system that allows for precise, programmable modifications to a wide range of microbial genomes. The economies of fermentation-based manufacturing are changing because of its quick acceptance in both academic and industry labs. CRISPR processes have been used to modify industrially significant bacteria, including the lactic acid producers, Clostridium spp., Escherichia coli, and Corynebacterium glutamicum, in order to increase the yields of bioethanol, butanol, succinic acid, acetone, and polyhydroxyalkanoate precursors. CRISPR-mediated promoter engineering and single-step multiplex editing have improved inhibitor tolerance, raised ethanol titers, and allowed for the de novo synthesis of terpenoids, flavonoids, and recombinant vaccines in yeasts, especially Saccharomyces cerevisiae and emerging non-conventional species. While enzyme and biopharmaceutical manufacturing use CRISPR for quick strain optimization and glyco-engineering, food and beverage fermentations benefit from starter-culture customization for aroma, texture, and probiotic functionality. Off-target effects, cytotoxicity linked to Cas9, inefficient delivery in specific microorganisms, and regulatory ambiguities in commercial fermentation settings are some of the main challenges. This review provides an industry-specific summary of CRISPR–Cas9 applications in microbial fermentation and highlights technical developments, persisting challenges, and industrial advancements. Full article

Neonatal calves possess an immature and naïve immune system and are reliant on the intake of maternal colostrum for the passive transfer of immunoglobulins. Maternal antibodies delivered to the calf via colostrum, are crucial to prevent calfhood diseases and death. Failure of transfer of passive immunity (FTPI) is a condition in which calves do not acquire enough maternal antibodies, mostly in the form of IgG, due to inadequate colostrum quality or delayed colostrum feeding. The diagnosis and risk factors for FTPI have been widely studied in dairy cattle; however, in beef calves, the research interest in the topic is relatively recent, and the most adequate diagnostic and preventative methods are still in development, making it difficult to define recommendations for the assessment and prevention of FTPI in cow–calf operations. The objective of this scoping review is to identify the published literature on best practices for colostrum management and transfer of passive immunity (TPI) in neonatal beef calves. The literature was searched using three electronic databases (CAB Direct, Scopus, and PubMed) for publications from 2003 to 2025. The search process was performed during the period from May to July 2023, and was repeated in January 2025. All screening processes were performed using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). A total of 800 studies were initially identified through database searches. After removing duplicates, 346 studies were screened based on their titles and abstracts, leading to the exclusion of 260 studies. The remaining 86 studies underwent full-text screening, and 58 studies were considered eligible for data extraction. Hand-searching the references from published review papers on the subject yielded an additional five studies, bringing the total to 63 included articles. The prevalence of FTPI has been estimated to be between 5.8% and 34.5% in beef calves. Factors studied related to colostrum management include quality and quantity of colostrum intake, the timing and method of colostrum feeding, and the microbial content of the colostrum. Studies on risk factors related to the calf include the topics calf sex, twin status, calf vigor, weight, month of birth, cortisol and epinephrine concentrations, and the administration of nonsteroidal anti-inflammatory drugs to calves after difficult calving. The dam-related risk factors studied include dam body condition score and udder conformation, breed, parity, genetics, prepartum vaccinations and nutrition, calving area and difficulty, and the administration of nonsteroidal anti-inflammatory drugs at C-section. Most importantly for beef systems, calves with low vigor and a weak suckling reflex are at high risk for FTPI; therefore, these calves should be given extra attention to ensure an adequate consumption of colostrum. While serum IgG levels of < 8 g/L or < 10 g/L have been suggested as cutoffs for the diagnosis of FTPI, 16 g/L and 24 g/L have emerged as cutoffs for adequate and optimal serum IgG levels in beef calves. Several field-ready diagnostics have been compared in various studies to the reference standards for measuring indicators of TPI in beef calves, where results often differ between models or manufacturers. Therefore, care must be taken when interpreting these results. Full article

Background: Breakthrough infections (BTIs) continue to occur among healthcare workers (HCWs) despite full COVID-19 vaccination, raising concerns about ongoing vulnerability in this high-risk group. In addition to initial BTIs, breakthrough reinfections (BTRs) have emerged as a challenge, with some HCWs experiencing multiple episodes of infection after vaccination. This study investigated the factors influencing breakthrough infection and reinfection rates among HCWs between January 2021 and December 2022 in Davao City, Philippines. Methods: This retrospective cohort study was conducted using secondary data from the Davao City Epidemiological Surveillance Unit, approved by the Department of Health. This study included 1011 fully vaccinated HCWs from various congressional districts. Results: BTI was observed in all HCWs included in the study. However, BTRs varied across occupational groups: medical technologists showed the highest reinfection rate (22.37%), followed by physicians (13.48%), and nurses/nurse aides (10.14%). Booster vaccination significantly reduced BTRs (5.83% vs. 11.18%, p = 0.0267). Occupation and institutional type were significant factors, with higher rates reported by physicians and in public hospitals (p = 0.0002 and p = 0.0041, respectively). The vaccine manufacturer, sex, age, and booster type showed no significant differences. Conclusion: These findings highlight the importance of targeted interventions for high-risk HCWs and emphasize the effectiveness of the booster vaccination. 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

Background: Since the massive outbreak of foot-and-mouth disease (FMD) in South Korea in 2010–2011, cloven-hoofed livestock have been immunized with serotype O and A vaccines across the country. Other serotypes of FMD vaccines were stockpiled in overseas FMD vaccine factories as antigen banks. Once a manufacturing facility has been established in South Korea, the overseas antigen banks will be replaced by domestic one. Therefore, this study aimed to evaluate the commercial potential of the previously developed SAT2 vaccine candidate (SAT2 ZIM-R). Methods: The optimal condition was determined at various virus concentrations, infection times, and pH levels, resulting in 0.01 MOI for SAT2 ZIM-R for 24 h infection at a pH of 7.5. Results: When the SAT2 ZIM-R virus was produced in flasks from 40 to 1000 mL in fivefold increments, all scales of production yielded > 7.0 µg/mL of antigens. Using a bioreactor, 5.6 µg/mL of antigens was recovered from a 1 L viral culture. The optimal conditions of viral inactivation kinetics were determined to be 1 mM of binary ethyleneimine (BEI) treatment at 26 °C for 24 h, with approximately 91% of the antigen being retained after virus inactivation. When the SAT2 ZIM-R experimental vaccine was administered twice to pigs, the neutralizing antibody titer increased approximately 500-fold after booster immunization. Conclusions: To the best of our knowledge, this is the first study to evaluate the antigen productivity, viral inactivation kinetics, and immunogenicity of the SAT vaccine strain in pigs. In the future, the SAT2 ZIM-R vaccine may be a useful candidate vaccine for a domestic antigen bank. Full article

The development of vaccines against viral infections has advanced rapidly over the past century, propelled by innovations in laboratory and molecular technologies. These advances have expanded the range of vaccine platforms beyond live-attenuated and inactivated vaccines to include recombinant platforms, such as subunit proteins and virus-like particles (VLPs), and more recently, mRNA-based vaccines, while also enhancing methods for evaluating vaccine performance. Despite these innovations, a persistent challenge remains: the inherent complexity and heterogeneity of immune responses continue to impede efforts to achieve consistently effective and durable protection across diverse populations. Single-cell technologies have emerged as transformative tools for dissecting this immune heterogeneity, providing comprehensive and granular insights into cellular phenotypes, functional states, and dynamic host–pathogen interactions. In this review, we examine how single-cell epigenomic, transcriptomic, proteomic, and multi-omics approaches are being integrated across all stages of vaccine development—from infection-informed discovery to guide vaccine design, to high-resolution evaluation of efficacy, and refinement of cell lines for manufacturing. Through representative studies, we highlight how insights from these technologies contribute to the rational design of more effective vaccines and support the development of personalized vaccination strategies. Full article