Innovative Vaccine Research Articles

Prokaryote- and Eukaryote-Based Expression Systems: Advances in Post-Pandemic Viral Antigen Production for Vaccines

This review addresses the ongoing global challenge posed by emerging and evolving viral diseases, underscoring the need for innovative vaccine development strategies. It focuses on the modern approaches to creating vaccines based on recombinant proteins produced in different expression systems, including bacteria, yeast, plants, insects, and mammals. This review analyses the advantages, limitations, and applications of these expression systems for producing vaccine antigens, as well as strategies for designing safer, more effective, and potentially ‘universal’ antigens. The review discusses the development of vaccines for a range of viral diseases, excluding SARS-CoV-2, which has already been extensively studied. The authors present these findings with the aim of contributing to ongoing research and advancing the development of antiviral vaccines.

Bridging One Health: Computational design of a multi-epitope messenger RNA vaccine for cross-species immunization against Nipah virus

Background and Aim: Nipah virus (NiV) poses a threat to human and animal health, particularly swine, which serve as primary vectors for human transmission. Despite its severe risks, no NiV vaccine currently exists for humans or animal hosts; thus, innovative vaccine development approaches that address cross-species transmission are required. This study was computationally designed to evaluate a multi-epitope messenger RNA (mRNA) vaccine targeting NiV for human and swine immunization. Materials and Methods: B and T lymphocyte epitopes were identified from NiV structural proteins using multiple epitope prediction tools. All epitopes were linked to form a multi-epitope construct, and various adjuvant combinations were analyzed for physicochemical properties and immune simulation. Molecular docking and dynamics were employed to visualize the construct’s interaction with a host immune receptor. Signal peptides were added to the construct, and mRNA sequences were generated using LinearDesign. The minimum free energies (MFEs) and codon adaptation indices (CAI) were used to select the final mRNA sequence of the vaccine construct. Results: Computational tools predicted 10 epitopes within NiV structural proteins that can be recognized by human and swine immune receptors. The construct with β-defensin 2 adjuvant was selected as the final immunogenic region after showing favorable immunogenicity profiles and physicochemical properties. The final vaccine sequence had higher MFE and CAI compared to the BioNTech/Pfizer BNT162b2 and Moderna mRNA-1273 vaccines. Conclusion: The multi-epitope mRNA vaccine designed in this study shows promising results as a potential NiV vaccine candidate. Further in vivo and in vitro studies are required to confirm the efficacy. Keywords: computational design, cross-species immunization, messenger RNA vaccine, multi-epitope, Nipah virus.

Health Catch-UP!: a realist evaluation of an innovative multi-disease screening and vaccination tool in UK primary care for at-risk migrant patients

BackgroundMigrants to the UK face disproportionate risk of infections, non-communicable diseases, and under-immunisation compounded by healthcare access barriers. Current UK migrant screening strategies are unstandardised with poor implementation and low uptake. Health Catch-UP! is a collaboratively produced digital clinical decision support system that applies current guidelines (UKHSA and NICE) to provide primary care professionals with individualised multi-disease screening (7 infectious diseases/blood-borne viruses, 3 chronic parasitic infections, 3 non-communicable disease or risk factors) and catch-up vaccination prompts for migrant patients.MethodsWe carried out a mixed-methods process evaluation of Health Catch-UP! in two urban primary healthcare practices to integrate Health Catch-UP! into the electronic health record system of primary care, using the Medical Research Council framework for complex intervention evaluation. We collected quantitative data (demographics, patients screened, disease detection and catch-up vaccination rates) and qualitative participant interviews to explore acceptability and feasibility.ResultsNinety-nine migrants were assessed by Health Catch-UP! across two sites (S1, S2). 96.0% (n = 97) had complete demographics coding with Asia 31.3% (n = 31) and Africa 25.2% (n = 25), the most common continents of birth (S1 n = 92 [48.9% female (n = 44); mean age 60.6 years (SD 14.26)]; and S2 n = 7 [85.7% male (n = 6); mean age 39.4 years (SD16.97)]. 61.6% (n = 61) of participants were eligible for screening for at least one condition and uptake of screening was high 86.9% (n = 53). Twelve new conditions were identified (12.1% of study population) including hepatitis C (n = 1), hypercholesteraemia (n = 6), pre-diabetes (n = 4), and diabetes (n = 1). Health Catch-UP! identified that 100% (n = 99) of patients had no immunisations recorded; however, subsequent catch-up vaccination uptake was poor (2.0%, n = 1). Qualitative data supported acceptability and feasibility of Health Catch-UP! from staff and patient perspectives, and recommended Health Catch-UP! integration into routine care (e.g. NHS health checks) with an implementation package including staff and patient support materials, standardised care pathways (screening and catch-up vaccination, laboratory, and management), and financial incentivisation.ConclusionsClinical Decision Support Systems like Health Catch-UP! can improve disease detection and implementation of screening guidance for migrant patients but require robust testing, resourcing, and an effective implementation package to support both patients and staff.

Preparing for future public health crises by fostering a conducive environment

Abstract Vaccination is considered one of the most cost-effective public health interventions. Zoonotic diseases, which are transmitted from animals to humans, represent an escalating global health concern. Environmental degradation, wildlife trade, and intensified farming practices have disrupted natural ecosystems. This has not only heightened the risk of pathogens crossing species barriers but exacerbated the migrant crisis and deepened global inequalities, as vulnerable populations disproportionally bear the environmental and health burdens. Despite decades of awareness about these risks, the COVID-19 pandemic highlighted our lack of preparedness. At the same time, vaccination hesitancy has been revealed as an important factor in implementing universal vaccination coverage at the population level. Urgency drove innovation. Within months, new multidisciplinary and interdisciplinary approaches were implemented that enhanced our capacity to understand, treat, and protect against the virus. This led to deploying novel technologies, curbing the crisis, and even opening the door to emerging health technologies across a wide spectrum of innovation, from new medicinal products, including vaccines, to evidence synthesis tools, including for modelling and forecasting. Shifting from emergency measures to long-term management of COVID-19, there lies a critical opportunity to strengthen resilience and to increase preparedness against future health threats. The EUVABECO project seeks to harness this momentum by initiating pilot projects that test innovative vaccination tools in evidence-based selected reference practices. These pilots are planned to use suitable theoretical frameworks and consensus meetings to design and develop comprehensive implementation plans that will be shared with EU MS, thereby enhancing Europe’s preparedness and response capabilities against communicable diseases.

3.I. Scientific session: Increasing EU preparedness and improving European Vaccination Beyond COVID-19: the EUVABECO approach

Abstract This workshop provides a platform for delegates to enhance their understanding of the interdisciplinary approach developed in the European Vaccination Beyond COVID-19 (EUVABECO) project, funded under the European Commission’s EU4Health programme. The project is to build and validate implementation plans for EU Member States (MS) to equip them with operational and technical tools to enhance vaccination practices both in routine vaccination and in case of future outbreaks. Validation will be based on innovative practices that emerged in the context of the COVID-19 pandemic. Ultimately, EUVABECO will provide MS with robust implementation plans for common tools to support said innovative vaccination practices, thus, enhancing preparedness and increasing resilience against future health threats in Europe and globally. Guided by two chairs, the workshop is structured around five brief interactive presentations to deliver the conceptualisation, methodologies, and early results and vision for vaccination beyond COVID-19. It is designed to highlight how project activities strengthen resilience and increase preparedness against communicable diseases across the EU and beyond its borders, whilst brokering dialogue on related public health priorities. The presentations will focus on: 1. Preparing for future public health crises by fostering a conducive environment. 2. Enhancing preparedness by developing robust implementation plans. 3. An interdisciplinary approach: Exploring the five dimensions (medical/clinical, social, industrial, modelling and forecasting, and digital) of the tools deployed by EUVABECO. 4. The vital role of stakeholders and of the National Immunization Technical Advisory Groups (NITAGs). 5. Future actions and a call for ongoing support and collaboration in a structured manner. The session will also give the opportunity to formally present EUVABECO’s multistakeholder approach and to formally launch the EU Vaccination Stakeholder Forum, where early access will be granted to EU MS for the various resources generate. This will allow the audience to give input about the needs of the broader public health community involved in vaccination across the EU, for the Stakeholder Forum to effectively promote and support: • The scaling up of existing implementation plans within MS; • The development of new implementation plans for additional tools; • Integration between public health and primary care; • Inform the targeted interaction with EU and MS bodies involved in related policies and decision-making. The presentations will be augmented by real-time polling to maximize participant engagement. This approach will maximize interaction whilst eliciting critical insights into stakeholders’ knowledge, attitudes, and practices concerning EUVABECO’s tools and strategies. This type of engagement will ensure effective knowledge transfer and a comprehensive understanding of the project’s objectives and implementation strategies. Key messages • Enhancing vaccination preparedness requires an evidence-based and harmonized set of tools to be deployed across EU MS. EUVABECO will deliver validated implementation plans to achieve this. • An interdisciplinary approach and multistakeholder engagement are critical for evidence-informed decision-making and harmonization to successfully deploy vaccination initiatives across the EU.

Influenza A as a True Zoonotic Pathogen: Transmission through Reservoir Hosts

Influenza A virus (IAV) represents a considerable global health threat due to its rapid mutation rates and broad host range, facilitating cross-species transmission and enabling the virus to evade immune defenses. This review explores the molecular mechanisms underlying IAV's pathogenicity, focusing on its zoonotic potential through reservoir hosts, such as wild birds and swine. The virus's ability to undergo antigenic shift and drift allows it to continually adapt to new hosts and environments, posing challenges for control and treatment. Current antiviral therapies are limited by the emergence of resistant strains, underscoring the necessity for innovative vaccine development and treatment strategies. By examining IAV's molecular evolution, immune evasion tactics, and transmission dynamics, this review highlights the critical need for enhanced surveillance, improved therapeutic options, and international cooperation to mitigate future outbreaks. A deeper understanding of these processes is essential to inform public health efforts and combat the persistent threat of IAV.

Mannose and Lactobionic Acid in Nasal Vaccination: Enhancing Antigen Delivery via C-Type Lectin Receptors.

Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access. This review focuses on cutting-edge approaches to enhance nasal vaccine delivery, particularly those targeting C-type lectin receptors (CLRs) like the mannose receptor and macrophage galactose-type lectin (MGL) receptor. It elucidates the roles of these receptors in antigen recognition and uptake by antigen-presenting cells (APCs), providing insights into optimizing vaccine delivery. While a comprehensive examination of targeted glycoconjugate vaccine development is outside the scope of this study, we provide key examples of glycan-based ligands, such as lactobionic acid and mannose, which can selectively target CLRs in the nasal mucosa. With the rise of new viral infections, this review aims to facilitate the design of innovative vaccines and equip researchers, clinicians, and vaccine developers with the knowledge to enhance immune defenses against respiratory pathogens, ultimately protecting public health.

From ancient remedies to modern miracles: tracing the evolution of vaccines and their impact on public health.

This review traces the development of vaccines from ancient times to the present, highlighting major milestones and challenges. It covers the significant impact of vaccines on public health, including the eradication of diseases such as smallpox and the reduction of others such as polio, measles, and influenza. The review provides an in-depth look at the COVID-19 vaccines, which were developed at unprecedented speeds due to the urgent global need. The study emphasizes the ongoing potential of vaccine development to address future global health challenges, demonstrating the critical role vaccines play in disease prevention and public health. Moreover, it discusses the evolution of vaccine technology, from live-attenuated and inactivated vaccines to modern recombinant and mRNA vaccines, showcasing the advancements that have enabled rapid responses to emerging infectious diseases. The review underscores the importance of continued investment in research and development, global collaboration, and the adoption of new technologies to enhance vaccine efficacy and coverage. By exploring historical and contemporary examples, the article illustrates how vaccines have transformed medical practice and public health outcomes, providing valuable insights into future directions for vaccine innovation and deployment.

COL6A6 Peptide Vaccine Alleviates Atherosclerosis through Inducing Immune Response and Regulating Lipid Metabolism in Apoe−/− Mice

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize Apoe−/− mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in Apoe−/− mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6Clow monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine.

Collaboration for new therapies: maximizing health and innovation.

Innovative medicines and vaccines can provide direct health benefits to patients and populations by preventing, treating and curing diseases, and also drive wider socioeconomic and productivity gains. However, researching and developing them is complex and risky. Funding for life sciences R&D has different sources: public, charitable/NGO, and private sector. We believe there is consensus that all are required, although there is less understanding about their respective roles, synergies, and funding priorities. The purpose of this paper is to provide an overview of the current life sciences innovation ecosystem in Europe, highlighting challenges for funding and innovation of new therapies and our proposed options to address these. The basis of this paper stems from the reflections made by the co-authors during a webinar with title "Collaboration for new therapies: maximising funding and innovation," in March 2023, with further targeted literature reviews. We identify eight challenges in the European life sciences ecosystem, some closely related, and nine options that we think might be helpful to address them. Each option on its own can have different levels of 'impact', but collectively will provide synergies among them, and thus maximize their impact. It is critical to ascertain how the strengths of each actor can be leveraged to bring new medicines/treatments to market, quicker and more efficiently. We need a trusted environment, with strategic collaborations between the public and private sectors, and policy initiatives and incentives should be targeted to strengthen the infrastructure with the aim of fostering such optimal alliances.

Structure-guided assembly of an influenza spike nanobicelle vaccine provides pan H1 intranasal protection.

Development of intranasal vaccines for respiratory viruses has gained popularity. However, currently only a live-attenuated influenza vaccine is FDA-approved for intranasal administration. Here, we focused on influenza virus as it circulates seasonally, has pandemic potential, and has vaccine formulations that present hemagglutinin (HA) in different structural arrangements. These display differences have not been correlated with induction of pan-H1 antibodies or shown to provide intranasal protection. Using electron microscopy, biochemistry and animal studies, we identified HA complexes arranged as lipid discs with multiple trimeric HAs displayed along the perimeter, termed spike nanobicelles (SNB). We utilized a structure-guided approach to synthesize in vitro assembled spiked nanobicelles (IA-SNB) from a classical 1934 H1N1 influenza virus. IA-SNBs elicited pan-H1 antibodies and provided protection against antigenically divergent H1N1 viruses via intranasal immunizations. Viral glycoprotein spikes displayed as SNBs could aid in combating antigenic variation and provide innovative intranasal vaccines to aid universal influenza vaccine development.

The Road Ahead: Advancing Antifungal Vaccines and Addressing Fungal Infections in the Post-COVID World.

In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.

Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E.

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine. Mice vaccinated with CS-Hc/E exhibited superior antibody titers compared to those receiving Hc/E alone. To develop a trivalent vaccine against BoNT/A, BoNT/B, and BoNT/E- key contributors to the vast majority of human botulism-we conjugated CS-Hc/E with a biotinylated atoxic chimeric protein incorporating neutralizing epitopes from BoNT/A and BoNT/B. This chimeric protein includes the binding domain of BoNT/A, along with the protease-inactive light chain and translocation domains of BoNT/B. The interaction between CS and biotin formed a stable tetrameric antigen, EBA. Vaccination with EBA in mice elicited robust antibody responses and provided complete protection against lethal doses of BoNT/A, BoNT/B, and BoNT/E. Our findings highlight EBA's potential as a stable and effective broad-spectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies.

Influenza B Virus Vaccine Innovation through Computational Design.

As respiratory pathogens, influenza B viruses (IBVs) cause a significant socioeconomic burden each year. Vaccine and antiviral development for influenza viruses has historically viewed IBVs as a secondary concern to influenza A viruses (IAVs) due to their lack of animal reservoirs compared to IAVs. However, prior to the global spread of SARS-CoV-2, the seasonal epidemics caused by IBVs were becoming less predictable and inducing more severe disease, especially in high-risk populations. Globally, researchers have begun to recognize the need for improved prevention strategies for IBVs as a primary concern. This review discusses what is known about IBV evolutionary patterns and the effect of the spread of SARS-CoV-2 on these patterns. We also analyze recent advancements in the development of novel vaccines tested against IBVs, highlighting the promise of computational vaccine design strategies when used to target both IBVs and IAVs and explain why these novel strategies can be employed to improve the effectiveness of IBV vaccines.

Strategic Resilience and Financial Analysis of Merck & Co., Inc.: Navigating Challenges and Opportunities in the Pharmaceutical Industry

This study provides a comprehensive analysis of Merck & Co., Inc. (MRK), a prominent player in the global pharmaceutical industry, known for its significant contributions to healthcare through the development of innovative drugs and vaccines. Merck's core focus areas include pharmaceuticals, vaccines, animal health, and healthcare services, with its flagship oncology drug Keytruda being a major revenue contributor. The company faces challenges such as regulatory changes in drug pricing and competition from biosimilars and generics. To mitigate these challenges, Merck has initiated restructuring plans, including the 2024 Restructuring Plan, to optimize operational efficiency and achieve significant cost savings. The paper also presents a comparison of Merck's financial performance with industry peers - Johnson & Johnson, AbbVie and Bristol-Myers Squibb - and evaluates liquidity, solvency and profitability metrics. Despite certain challenges, Merck's robust market positioning, strategic acquisitions, and active involvement in the development of COVID-19 vaccines and therapeutics underscore its potential for sustainable growth. Overall, the study concludes that Merck's strategic investments, coupled with its strong financial position and proactive restructuring efforts, make it an attractive investment prospect, particularly in its core therapeutic areas of oncology and immunology. This paper suggests that future research could delve deeper into the long-term impact of R&D investments, the intricacies of restructuring plans, and evolving market trends to provide a more nuanced understanding of Merck's strategic planning.

Viral Vector-Based Chlamydia trachomatis Vaccines Encoding CTH522 Induce Distinct Immune Responses in C57BL/6J and HLA Transgenic Mice.

Chlamydia trachomatis remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. In this study, we evaluated two novel MVA-based recombinant vaccines expressing spCTH522 and CTH522:B7 antigens. Our results show that while both vaccines induced CD4+ T-cell responses in C57BL/6J mice, they failed to generate antigen-specific systemic CD8+ T cells. Only the membrane-anchored CTH522 elicited strong IgG2b and IgG2c antibody responses. In an HLA transgenic mouse model, both recombinant MVAs induced Th1-directed CD4+ T cell and multifunctional CD8+ T cells, while only the CTH522:B7 vaccine generated antibody responses, underscoring the importance of antigen localization. Collectively, our data indicate that distinct antigen formulations can induce different immune responses depending on the mouse strain used. This research contributes to the development of effective vaccines by highlighting the importance of careful antigen design and the selection of appropriate animal models to study specific vaccine-induced immune responses. Future studies should investigate whether these immune responses provide protection in humans and should explore different routes of immunization, including mucosal and systemic immunization.

Revamping Hepatocellular Carcinoma Immunotherapy: The Advent of Microbial Neoantigen Vaccines.

Immunotherapy has revolutionized the treatment paradigm for hepatocellular carcinoma (HCC). However, its efficacy varies significantly with each patient's genetic composition and the complex interactions with their microbiome, both of which are pivotal in shaping anti-tumor immunity. The emergence of microbial neoantigens, a novel class of tumor vaccines, heralds a transformative shift in HCC therapy. This review explores the untapped potential of microbial neoantigens as innovative tumor vaccines, poised to redefine current HCC treatment modalities. For instance, neoantigens derived from the microbiome have demonstrated the capacity to enhance anti-tumor immunity in colorectal cancer, suggesting similar applications in HCC. By harnessing these unique neoantigens, we propose a framework for a personalized immunotherapeutic response, aiming to deliver a more precise and potent treatment strategy for HCC. Leveraging these neoantigens could significantly advance personalized medicine, potentially revolutionizing patient outcomes in HCC therapy.

The transmission route of hepatitis A, B, and C virus and its pathological changes on the liver

This study explored the globally prevalent pathogens, hepatitis viruses, and their significant impact on human health. This article mainly focuses on HAV, HBV, and HCV, aiming to provide a comprehensive reference for future studies. HAV is mainly transmitted through the gastrointestinal tract, while HBV and HCV are mainly transmitted through blood, body fluids, sexual contact, and mother-to-child transmission. Pathologically, HAV is mostly acute, while HBV and HCV tend to be chronic, which can easily lead to cirrhosis and even liver cancer. Analyzing the transmission mechanism and pathological changes of HAV, HBV, and HCV is crucial for preventing and controlling viral transmission, accurate diagnosis and treatment, formulating public health policies, and public health education. Understanding this information will help reduce the prevalence of hepatitis, improve treatment outcomes, and promote public health. However, the analysis of the structure of these viruses in existing studies is not sufficient. Future studies will further deepen the understanding of HAV, HBV, and HCV, promote vaccine and treatment innovation, and provide stronger support for the prevention and treatment of hepatitis.

Safety, tolerability, and immunogenicity of WGc-043 in subjects with EBV-positive cancers: Results from an investigator-initiated trial.

139 Background: The Epstein-Barr virus (EBV) persists and spreads after infection in humans, leading to the occurrence and metastasis of a variety of cancers, posing great challenges in the treatment of cancer.. Conventional cancer therapies tend to have limited success and significant side effects. Therefore, there is an urgent need to develop more safe and efficient treatments such as innovative mRNA vaccines, which provide a new approach to cancer immunotherapy. WGc-043, an mRNA vaccine targeting EBV-positive tumor associated antigens, was evaluated for safety, tolerability, and immunogenicity in a prospective, single-center, investigator-initiated study. Methods: The study included 12 patients aged ≥18 with EBV-positive recurrent or metastatic nasopharyngeal carcinoma. Eligibility criteria included at least one measurable lesion, ECOG performance status 0-1, expected survival greater than three months, and no autoimmune disease. Participants were divided into three dose cohorts (25 μg, 50 μg, 100 μg) and received five administrations followed by optional continued monthly treatment of WGc-043 by intramuscular injection. The study assessed safety by adverse event monitoring, immune response based on the peripheral blood and tumor tissue sample analysis and efficacy according to imaging guidelines and irRECIST version 1.1. Results: The study results demonstrated that WGc-043 had a favorable safety profile with only grade 1 or 2 adverse events and fever (4/12) reported as the most common adverse event. Notably, two patients achieved partial response (PR) and five patients had stable disease (SD), highlighting the potential clinical efficacy of WGc-043. In addition, most (91.7%) subjects showed a significant reduction in plasma EBV DNA levels after administration. Immunogenicity analysis using IFN-γ ELISpot showed that 8 (66.7%) of the 12 enrolled patients developed strong specific immune responses against EBV-associated antigens, indicating that WGc-043 is a potent immunotherapy. Conclusions: This exploratory study underscores the safety and potential efficacy of WGc-043 as an mRNA vaccine for EBV-associated cancers, demonstrating its ability to induce specific immune responses and achieve substantial disease control in a challenging patient population, although further studies in larger clinical trials are needed. These results not only support the advancement of WGc-043 as a candidate for immunotherapy in EBV-positive cancers, but also highlight the translational potential of mRNA vaccine technology in the oncology landscape. Clinical trial information: NCT05714748 . [Table: see text]

Lessons from the COVID-19 Pandemic: Promoting Vaccination and Public Health Resilience, a Narrative Review.

The COVID-19 pandemic has underscored the critical importance of adaptable and resilient public health systems capable of rapid response to emerging health crises. This paper synthesizes the lessons learned from the COVID-19 vaccination campaign and explores strategies to enhance vaccine uptake in the post-pandemic era. Key challenges identified include logistical, economic, sociocultural, and policy dimensions that impact vaccination efforts, particularly in low-resource settings. The analysis highlights the need for resilient supply chains, effective communication, community engagement, and equitable access to healthcare resources. The rapid development and deployment of mRNA vaccines exemplify the potential of innovative vaccine technologies, though public trust and acceptance remain crucial. Strategies such as partnerships with local leaders, tailored messaging, and integration of digital tools are essential for combating vaccine hesitancy. By applying these insights, future vaccination campaigns can be more efficient, equitable, and resilient, ultimately improving public health outcomes globally. This paper aims to inform policy and practice, ensuring that public health strategies are evidence based and context specific, thus better preparing for future health challenges.