Search Results (1,424)

Deoxyribonucleic acid (DNA) vaccines have re-emerged as a versatile and scalable platform by advances in synthetic biology and delivery systems, positioning them as powerful tools in the post-mRNA vaccine era. Historically considered less potent than viral or mRNA-based platforms, recent breakthroughs have dramatically improved their immunogenicity, safety, and precision. These innovations include synthetic gene circuits, self-amplifying DNA (saDNA), and DNA-encoded monoclonal antibodies (DMAbs), which enable programmable expression and robust immune activation. Clinically, DNA vaccines are expanding into diverse applications, from infectious disease prevention to therapeutic cancer immunotherapy and treatment of immune-mediated conditions. Compared to mRNA vaccines, DNA vaccines offer compelling advantages in terms of thermal stability, ease of manufacturing, and long-term storage. Furthermore, novel adjuvants, electroporation methods, and formulation strategies such as lyophilization and encapsulation continue to broaden their clinical potential. This review explores the full scope of DNA vaccine technology and its engineering foundations, emerging disease applications, and interdisciplinary innovations, while evaluating its comparative performance and future role in global vaccine strategy. With an emphasis on both mechanistic insights and translational feasibility, we propose a roadmap to integrate DNA vaccines into the next generation of precision immunotherapy. Full article

Dengue is a rapidly spreading mosquito-borne viral infection, with increasing reports of outbreaks globally. According to the World Health Organization (WHO), by 30 April 2024, over 7.6 million dengue cases were reported, including 3.4 million confirmed cases, more than 16,000 severe cases, and over 3000 deaths. As dengue remains endemic in many regions, there is a critical need for the development of new vaccines and manufacturing processes that are efficient, cost-effective, and capable of meeting growing demand. In this study, we explore an alternative process development pathway for the future manufacturing of a dengue vaccine, utilizing Komagataella phaffii (Pichia pastoris) as the host organism, one of the most promising candidates for the expression of heterologous proteins in vaccine development. It combines the speed and ease of highly efficient prokaryotic platforms with some key capabilities of mammalian systems, making it ideal for scalable and cost-effective production. The key outcomes of our research include (i) demonstrating the versatility of the Komagataella phaffii platform in the production of dengue viral-like particles (VLPs); (ii) optimizing the culture process using Design of Experiments (DoE) approaches in small-scale bioreactors; (iii) developing a novel purification platform for enveloped VLPs (eVLPs), and (iv) establishing alternative biophysical characterization methods for the dengue vaccine prototype. These findings provide a promising foundation for efficient and scalable production of dengue vaccines, addressing both technical and operational challenges in vaccine manufacturing. Full article

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

Nano-based drug delivery systems present a promising approach to improve the efficacy and safety of therapeutics by enabling targeted drug transport and controlled release. In parallel, computational approaches—particularly Molecular Dynamics (MD) simulations and Artificial Intelligence (AI)—have emerged as transformative tools to accelerate nanocarrier design and optimise their properties. MD simulations provide atomic-to-mesoscale insights into nanoparticle interactions with biological membranes, elucidating how factors such as surface charge density, ligand functionalisation and nanoparticle size affect cellular uptake and stability. Complementing MD simulations, AI-driven models accelerate the discovery of lipid-based nanoparticle formulations by analysing vast chemical datasets and predicting optimal structures for gene delivery and vaccine development. By harnessing these computational approaches, researchers can rapidly refine nanoparticle composition to improve biocompatibility, reduce toxicity and achieve more precise drug targeting. This review synthesises key advances in MD simulations and AI for two leading nanoparticle platforms (gold and lipid nanoparticles) and highlights their role in enhancing therapeutic performance. We evaluate how in silico models guide experimental validation, inform rational design strategies and ultimately streamline the transition from bench to bedside. Finally, we address key challenges such as data scarcity and complex in vivo dynamics and propose future directions for integrating computational insights into next generation nanodelivery systems. Full article

Chronic viral infections and virus-induced cancers have been actively studied for decades, with many significant advancements in basic science, disease cure, treatment, and prevention. Yet, today, these infections and pathologies remain major contributors to morbidity and mortality worldwide. The international online conference “VIRCAN2024: Chronic viral infections and cancer, openings for Vaccines and Cure” aimed to address the remaining issues, present the research carried out in this broad field, and prognose directions for its development. The conference covered oncogenicity mechanisms and new approaches in the development of treatments and vaccines. VIRCAN2024 was held on the platform of Riga Stradins University, Riga, Latvia. The conference was supported by the Latvian Science Council grant “Human papillomavirus genome associated correlates of disease progression and treatment response for cervical neoplasms and cancer”, and the scientific journal Vaccines (MDPI). This report summarizes the lectures and presentations given at the conference. 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

Background/Objectives: Survey administration mode may significantly influence responses on polarizing health topics, yet this methodological factor remains understudied in vaccine hesitancy research. Understanding how data collection methods affect parental attitudes toward childhood vaccination is crucial for accurate public health surveillance and intervention design. Methods: This comparative cross-sectional study examined parental attitudes toward childhood vaccination using both paper-based (n = 487) and online (n = 386) survey administration among 873 parents. This study employed multivariate logistic regression analysis to assess differences between survey modes while controlling for demographic variables. Results: Key outcomes included general vaccination support, belief in vaccine–autism links, preference for natural immunity, and communication comfort with healthcare providers. Substantial differences emerged between survey modes. Online respondents showed significantly lower vaccination support (61.92% vs. 88.48%, p < 0.001), higher belief in the vaccine–autism link (37.31% vs. 16.77%, p < 0.001), and greater endorsement of natural immunity over vaccination (38.08% vs. 12.50%, p < 0.001). After adjusting for demographics, online respondents had 5 times lower odds of supporting childhood vaccination (OR = 0.20, 95% CI: 0.13–0.30) and nearly 5 times higher odds of preferring natural immunity (OR = 4.67, 95% CI: 3.19–6.95). Online respondents were also less likely to feel comfortable discussing vaccines with healthcare providers (51.0% vs. 72.7%, p < 0.001). Conclusions: Survey administration mode substantially influences measured parental vaccine attitudes, with online platforms capturing more vaccine-skeptical responses. These findings have critical implications for public health research methodology and suggest that mixed-mode survey designs or statistical adjustments may be necessary to obtain representative population estimates of vaccine hesitancy. 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

Background/Objectives: The continued evolution and cross-species transmission of clade 2.3.4.4b H5Nx highly pathogenic avian influenza (HPAI) viruses underscores the need for broadly protective vaccines in swine, a key intermediary host. This study aimed to evaluate systemic and mucosal immune responses elicited by adenoviral-vectored (Ad) vaccines encoding a centralized consensus hemagglutinin antigen (H5CC) in mice and swine. Methods: We constructed H5CC-based vaccines that were delivered using replication-defective (Ad5 and Ad6) and replication-competent (Ad28 and Ad48) human adenoviral vectors. Using a serotype-switched prime-boost strategy, vaccines were delivered intramuscularly (IM) or intranasally (IN) in mice and swine. We determined humoral, mucosal, and cell-mediated immune responses by hemagglutination inhibition (HI), microneutralization assay (MNA), ELISA, and IFN-γ ELISpot. Protective efficacy was evaluated by lethal H5N1 challenge in mice. Results: All vaccine strategies and routes induced significant levels of anti-H5 immunity. Ad5/Ad6 IM immunization elicited strong systemic IgG and MNA titers and robust T cell responses. IN delivery with Ad5/Ad6 induced superior mucosal IgA levels in lungs and nasal secretion. In swine, Ad5/Ad6 IM conferred the highest MNA titer and T cell responses, while the IN route enhanced mucosal IgA. The Ad28/Ad48 vaccines induced immunity in a similar pattern as compared to the Ad5/Ad6 strategy, but to a slightly lesser degree, in general. The commercial H1/H3 swine influenza vaccine failed to elicit cross-protective immunity. All H5CC vaccinated mice survived lethal H5N1 challenge without weight loss. Conclusions: Adenoviral-vectored H5CC vaccines elicit broad, cross-clade immunity with route-dependent immune profiles. IM vaccination is optimal for systemic and cellular responses, while IN delivery enhances mucosal immunity. These findings support the advancement of adenoviral platforms for influenza control in swine and pandemic preparedness. 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

Immunotherapy, particularly approaches that combine tumor-specific vaccines with immune checkpoint modulation, represents a promising strategy for overcoming tumor immune evasion. While most mRNA-based cancer vaccines focus solely on antigen delivery, there is a need for platforms that simultaneously enhance antigen presentation and modulate the tumor microenvironment to increase therapeutic efficacy. This study presents a novel dual-nanolipid exosome (NLE) platform that simultaneously delivers MUC1 mRNA and CTLA-4-targeted siRNA in a single system. These endogenous lipid-based nanoparticles are structurally designed to mimic exosomes and are modified with mannose to enable selective targeting to dendritic cells (DCs) via mannose receptors. The platform was evaluated both in vitro and in vivo in terms of mRNA encapsulation efficiency, nanoparticle stability, and uptake by DCs. The co-delivery platform significantly enhanced antitumor immune responses compared to monotherapies. Flow cytometry revealed a notable increase in tumor-infiltrating CD8⁺ T cells (p < 0.01), and ELISPOT assays showed elevated IFN-γ production upon MUC1-specific stimulation. In vivo CTL assays demonstrated enhanced MUC1-specific cytotoxicity. Combined therapy resulted in immune response enhancement compared to vaccine or CTLA-4 siRNA alone. The NLE platform exhibited favorable biodistribution and low systemic toxicity. By combining targeted delivery of dendritic cells, immune checkpoint gene silencing, and efficient antigen expression in a biomimetic nanoparticle system, this study represents a significant advance over current immunotherapy strategies. The NLE platform shows strong potential as a modular and safe approach for RNA-based cancer immunotherapy. Full article

Background: Geographic information systems (GIS) are a promising tool for mapping vaccination coverage and identifying missed communities, yet their use in low- and middle-income countries (LMICs) remains limited. In settings without standardized addresses such as schools or outreach sites, innovative methods are needed to collect and analyse spatial data. Schools offer a unique platform for identifying under-vaccinated children missed by routine or campaign efforts. Methods: During a pilot school vaccination screening program in Zambia, GIS reference maps of health facility catchment areas were developed from hand-drawn sketch maps, catchment area shapefiles, and coordinates of prominent landmarks. These maps were iteratively refined with input from local health staff. In caregiver interviews, data collectors used the maps to identify the child’s zone of residence within the health facility catchment area. Vaccination status was extracted from paper registries used during screening. Geographic heat maps were generated in ArcGIS to visualize under-vaccination by zone. Results: Of 535 children screened across 25 zones, 29% were under-vaccinated. Under-vaccination varied by zone, with clusters of missed children identified, for example, 50% of children in Kabushi Zone 6 were under-vaccinated, compared with much lower rates elsewhere. Conclusions: Pairing school-based vaccination checks with GIS mapping offers a scalable approach to identifying missed communities in LMICs. This method enables spatial analysis without household visits, supporting targeted immunization planning where traditional data systems fall short. However, because the study was limited to children enrolled in five purposively selected schools, out-of-school children and those in other schools were not represented. This selection bias may underestimate the true extent of under-vaccination, and future evaluations should incorporate broader and more representative populations. Full article

Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions. Full article

Background/Objectives: The pandemic caused by SARS-CoV-2 boosted the development of different vaccine models. In parallel, yeasts stand out as a vaccine platform in healthcare biotechnology. Species such as Saccharomyces cerevisiae and Pichia pastoris can express heterologous proteins, which are capable of inducing specific antibodies and can perform as an attractive vaccine vehicle with immunomodulating properties due to their cell wall composition. Furthermore, the yeast surface display system facilitates antigen presentation to immune cells. We developed an oral vaccine based on P. pastoris displaying a synthetic antigen composed of Spike and Nucleocapsid epitopes. Methods: The vaccine was administered to BALB/c mice. Systemic immune response was measured through antibody detection in blood samples, and mucosal immunity was assessed via IgA levels in feces. Histopathological analysis of intestinal and gastric tissues was also conducted. Results: The yeast-based vaccine elicited a humoral immune response, reflected in the production of neutralizing antibodies and elevated levels of IgG2a and IgG2. No structural alterations or pathological changes were observed in gastrointestinal tissues. Conclusions: This study demonstrates the feasibility of using P. pastoris as an oral vaccine delivery system, supporting previous findings with other yeast species such as Saccharomyces cerevisiae, and highlighting its potential in developing effective mucosal vaccines. Full article

Influenza remains a major health threat due to its high contagiousness and global spread, affecting not only humans but also agricultural livestock and wild animals through transmission via migratory birds. Despite over 70 years of vaccination, influenza still creates epidemics and pandemics, and the ongoing use of vaccination is an essential but currently insufficient strategy. In this study, we assessed the immunogenicity and efficacy of an AP205 virus-like particle (VLP) carrying the HA head domain of the A/PR8/H1N1 strain, administered intranasally and subcutaneously in mice. For this purpose, the entire head region of A/PR8/H1N1 was genetically integrated into a sterically improved version of AP205, which exhibits capsid monomers fused into a dimer, thereby offering inexpensive and scalable production processes. The vaccine induced strong systemic anti-HA IgG and IgA antibodies via both routes, with no significant difference in the levels of IgG. Both immunisation strategies induced protection against a lethal challenge with H1PR8 mouse-adapted influenza virus. The findings demonstrate the potential of the AP205 VLP platform for HA1-based influenza vaccines and its applicability for controlling influenza in both humans and livestock. Full article