Next-Generation mRNA Vaccines in Melanoma: Advances in Delivery and Combination Strategies

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has facilitated the clinical implementation of messenger RNA (mRNA) vaccines. The successful development of lipid nanoparticles (LNPs)-based mRNA vaccines, such as Spikevax (Moderna) and...

Absence of Humoral Response After Two-Dose SARS-CoV-2 Messenger RNA Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: A Case Series.

Impaired SARS-CoV-2 mRNA Vaccine Antibody Response in Chronic Medical Conditions: A Real-World Analysis

Messenger RNA (mRNA) vaccines constitute an emerging therapeutic method with the advantages of high safety and efficiency as well as easy synthesis; thus, they have been widely used in various human diseases, especially in malignant cancers. However, the mRNA vaccine technology has some limitations, such as instability and low transitive efficiency in vivo, which greatly restrict its application. The development of nanotechnology in the biomedical field offers new strategies and prospects for the early diagnosis and treatment of human cancers. Recent studies have demonstrated that Lipid nanoparticle (LNP)-based mRNA vaccines can address the poor preservation and targeted inaccuracy of mRNA vaccines. As an emerging cancer therapy, mRNA vaccines potentially have broad future applications. Unlike other treatments, cancer mRNA vaccines provide specific, safe, and tolerable treatments. Preclinical studies have used personalized vaccines to demonstrate the anti-tumor effect of mRNA vaccines in the treatment of various solid tumors, including colorectal and lung cancer, using these in a new era of therapeutic cancer vaccines. In this review, we have summarized the latest applications and progress of LNP-based mRNA vaccines in cancers, and discussed the prospects and limitations of these fields, thereby providing novel strategies for the targeted therapy of cancers.

Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series

BackgroundAlthough messenger RNA (mRNA) vaccines have unique advantages against multiple tumors, mRNA vaccine targets in stomach adenocarcinoma (STAD) remain unknown. The potential effectiveness of mRNA vaccines is closely associated with the tumor immune infiltration microenvironment. The present study aimed to identify tumor antigens of STAD as mRNA vaccine targets and systematically determine immune subtypes (ISs) of STAD that might be suitable for immunotherapy.MethodsGene expression profiles and clinical data of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA; n = 409) and the Gene Expression Omnibus (GEO; n = 433), and genomic data were extracted from cBioPortal. Differential gene expression was analyzed using the limma package, genetic alterations were visualized using maftools, and prognosis was analyzed using ToPP. Correlations between gene expression and immune infiltration were calculated using TIMER software, and potential ISs were identified using ConsensusClusterPlus. Functional enrichment was analyzed in clusterProfiler, and r co-expression networks were analyzed using the weighted gene co-expression network analysis (WGCNA) package in R.ResultsOverexpression of the prognostic and highly mutated antigens ADAMTS18, COL10A1, PPEF1, and STRA6 was associated with infiltration by antigen-presenting cells in STAD. Five ISs (IS1–IS5) in STAD with distinct prognoses were developed and validated in TCGA and GEO databases. The tumor mutational burden and molecular and clinical characteristics significantly differed among IS1–IS5. Both IS1 and IS2 were associated with a high mutational burden, massive infiltration by immune cells, especially antigen-presenting cells, and better survival compared with the other subtypes. Both IS4 and IS5 were associated with cold immune infiltration and correlated with advanced pathological stages. We analyzed the immune microenvironments of five subtypes of immune modulators and biomarkers to select suitable populations for mRNA vaccination and established four co-expressed key modules to validate the characteristics of the ISs. Finally, the correlation of these four mRNA vaccine targets with the transcription factors of DC cells, including BATF3, IRF4, IRF8, ZEB2, ID2, KLF4, E2-2, and IKZF1, were explored to reveal the underlying mechanisms.ConclusionsADAMTS18, COL10A1, PPEF1, and STRA6 are potential mRNA vaccine candidates for STAD. Patients with IS1 and IS2 are suitable populations for mRNA vaccination immunotherapy.

A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety

Messenger RNA (mRNA) vaccines are emerging as powerful tools in oncology, extending their success from infectious diseases to cancer immunotherapy. Globally, over 13.5 billion mRNA vaccine doses have been administered, establishing a strong safety and adaptability record. In surgical oncology, where 25–40% of patients experience postoperative recurrence, mRNA vaccines offer a new avenue for durable immune surveillance. Personalized mRNA vaccines encoding tumor-specific neoantigens have shown 44% objective response rates in melanoma and a 50% reduction in recurrence when combined with checkpoint inhibitors. In pancreatic cancer, early-phase data demonstrated neoantigen-specific T-cell expansion in half of the recipients, improving relapse-free intervals. Moreover, emerging evidence links gut microbiota composition with mRNA vaccine pharmacodynamics, influencing T-cell activation by up to 35%, as demonstrated in recent pharmacomicrobiomic analyses. These findings suggest that integrating mRNA vaccines into peri-operative cancer care could transform postoperative outcomes through precision immunotherapy. Collectively, this paradigm marks a new era in neoplasm immunotherapy and precision surgical oncology, bridging immune science with personalized care.

Messenger RNA (mRNA) vaccines have quickly become a potent tool in cancer immunotherapy, with the potential to personalise cancer treatment and get around many of the drawbacks of conventional therapies. With an emphasis on their processes, technological developments, and clinical applications, this study examines the scientific breakthroughs and difficulties surrounding mRNA cancer vaccines. We begin by investigating the ways in which mRNA vaccines work to stimulate the immune system, encode antigens specific to tumours, and elicit a potent anti-tumor response. We also look at the variety of mRNA vaccines which are currently being deployed and emphasize their successes in clinical studies, especially when combined with immune checkpoint inhibitors. The effectiveness and safety of these vaccines have been significantly increased by technological developments, such as enhancements in mRNA stability, design, and delivery systems (such as lipid nanoparticles and polyplexes). Emerging technologies like circular RNA and self-amplifying present promising opportunities for enduring and more potent therapies. But there are still limitations with mRNA vaccines, such as stability, immunogenicity, degradation, and effective in vivo delivery. Concerns about possible adverse effects and safety in long-term applications are also covered in this review. Despite these obstacles, novel approaches are being developed to boost antigen expression, optimize delivery systems, and improve mRNA stability, establishing mRNA vaccines as a crucial component of tailored cancer immunotherapy. These developments provide the foundation for upcoming advances in mRNA vaccine technology and represent a major breakthrough in the fight against cancer.

BackgroundOur group has investigated plasmid DNA (pDNA) vaccines encoding tumor-associated antigens for the treatment of cancer. However, DNA vaccines as monotherapies have generally been perceived as being less immunogenic in...

Over the past several decades, messenger RNA (mRNA) vaccines have progressed from a scepticism-inducing idea to clinical reality. In 2020, the COVID-19 pandemic catalysed the most rapid vaccine development in history, with mRNA vaccines at the forefront of those efforts. Although it is now clear that mRNA vaccines can rapidly and safely protect patients from infectious disease, additional research is required to optimize mRNA design, intracellular delivery and applications beyond SARS-CoV-2 prophylaxis. In this Review, we describe the technologies that underlie mRNA vaccines, with an emphasis on lipid nanoparticles and other non-viral delivery vehicles. We also overview the pipeline of mRNA vaccines against various infectious disease pathogens and discuss key questions for the future application of this breakthrough vaccine platform.

Messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, improving the immunogenicity and durability of mRNA vaccines remains a challenge. To elicit optimal immune responses, integrating antigen-encoded mRNA and immunostimulatory adjuvants into a single formulation is a promising approach to enhancing the efficacy of mRNA vaccines. Here, we report an adjuvant strategy to enhance the efficacy of mRNA vaccines by co-loading mRNA encoding the antigen (rabies virus glycoprotein, RABV-G) and mRNA encoding IL-7 into lipid nanoparticles, achieving co-delivery to the same antigen-presenting cells. A single immunization with G&IL-7 mRNA vaccine elicited robust humoral immune responses in mice and conferred complete protection against RABV challenge. Notably, the high levels of neutralizing antibody induced by the G&IL-7 mRNA vaccine were maintained for at least 6 months, providing mice with long-term significant and complete protection against RABV. Additionally, IL-7 also enhanced antibody responses against the SARS-CoV-2. These data demonstrate that IL-7 is a potent mRNA vaccine adjuvant that can provide the required immune stimulation in various mRNA vaccine formulations.Graphical

Messenger RNA (mRNA) vaccines have emerged as a transformative platform in modern vaccinology. mRNA vaccine is a powerful alternative to traditional vaccines due to their high potency, safety, and efficacy, coupled with the ability for rapid clinical development, scalability and cost-effectiveness in manufacturing. Initially conceptualized in the 1970s, the first study about the effectiveness of a mRNA vaccine against influenza was conducted in 1993. Since then, the development of mRNA vaccines has rapidly gained significance, especially in combating the COVID-19 pandemic. Their unprecedented success during the COVID-19 pandemic, as demonstrated by the Pfizer-BioNTech and Moderna vaccines, highlighted their transformative potential. This review provides a comprehensive analysis of the mRNA vaccine technology, detailing the structure of the mRNA vaccine and its mechanism of action in inducing immunity. Advancements in nanotechnology, particularly lipid nanoparticles (LNPs) as delivery vehicles, have revolutionized the field. The manufacturing processes, including upstream production, downstream purification, and formulation are also reviewed. The clinical progress of mRNA vaccines targeting viruses causing infectious diseases is discussed, emphasizing their versatility and therapeutic potential. Despite their success, the mRNA vaccine platform faces several challenges, including improved stability to reduce dependence on cold chain logistics in transport, enhanced delivery mechanisms to target specific tissues or cells, and addressing the risk of rare adverse events. High costs associated with encapsulation in LNPs and the potential for unequal global access further complicate their widespread adoption. As the world continues to confront emerging viral threats, overcoming these challenges will be essential to fully harness the potential of mRNA vaccines. It is anticipated that mRNA vaccines will play a major role in defining and shaping the future of global health.

Messenger RNA (mRNA) vaccine technology has revolutionized the field of immunization, offering a non-infectious, non-genome-integrating platform that addresses many limitations of traditional vaccine modalities. Recent advancements in chemical modifications, delivery systems, and manufacturing processes have enhanced the stability, efficacy, and safety of RNA-based therapeutics, expanding their application beyond infectious diseases to include genetic disorders, cancer, and rare diseases. Central to the success of RNA vaccines is their ability to orchestrate a finely tuned immune response, leveraging both innate and adaptive immunity to achieve robust and durable protection. This review synthesizes current knowledge on the immunological mechanisms underpinning RNA vaccine efficacy, with a focus on the roles of pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) in sensing exogenous RNA, the impact of RNA modifications and manufacturing impurities on innate immune activation, and the subsequent cytokine and chemokine milieu that shapes adaptive responses. We also discuss the dual role of lipid nanoparticle (LNP) delivery systems as both carriers and adjuvants, highlighting their contribution to the vaccine’s immunogenicity and reactogenicity profile. Understanding these complex immune interactions is critical for optimizing RNA vaccine design, minimizing adverse effects, and expanding their therapeutic potential. This review aims to provide a comprehensive overview of the immune symphony orchestrated by RNA vaccines and to identify key areas for future research to further refine and expand the utility of this transformative technology.

Immunogenicity of a third COVID-19 messenger RNA vaccine dose in primary immunodeficiency disorder patients with functional B-cell defects