Immunization with radiation-attenuated sporozoites (RAS) drives effective sterilizing immunity against liver-stage Plasmodium infection. However, protection is compromised in individuals living in malaria endemic regions and the mechanisms of vaccine failure are unclear. Here we show that previous blood-stage exposure in a mouse model of Plasmodium yoelii infection compromises Plasmodium berghei RAS-induced essential CD8+ T cell responses and subsequent protection. The persisting malarial pigment haemozoin mediates impaired CD8+ T cell responses owing to impaired antigen uptake by dendritic cells, leading to reduced T cell activation. We designed a lipid nanoparticle-encapsulated mRNA vaccine that encodes a string of Plasmodium CD8+ T cell epitopes, which overcomes the defective T cell response and restores protection in Plasmodium-exposed mice. A combined RAS-plus-mRNA vaccine regimen enhances liver-resident memory T cells and protection in murine malaria-experienced hosts. The identification of haemozoin as a potential obstacle to vaccine efficacy in malaria endemic areas can inform the design of more effective malaria vaccines.

Advancements in breast cancer mRNA vaccines: Current development and future prospects.

Lipid-free, thermostable mRNA vaccines prepared using atomic layer deposition.

A single extracellular vesicle-based platform supporting both RBD protein and mRNA vaccination against SARS-CoV-2.

Humoral and cellular immunogenicity of sequential heterogeneous bivalent SARS-CoV-2 vaccinations in long-term care and retirement home residents.

Insights into RAS-driven melanoma and its therapeutic implications.

mRNA vaccines targeting Leptospira immunoglobulin-like proteins confer partial protection in a hamster model of leptospirosis.

Enhanced subchronic cardiac stress of high doses of a novel SARS-CoV-2 mRNA vaccine candidate in streptozotocin-induced diabetic mice.

Herpes zoster mRNA vaccine elicits superior immune responses over licensed vaccines with a favorable safety profile in animal models.

A new fucosylated glucuronoxylomannan from the fruit bodies of Tremella aurantia: structural characterization and immunoenhancing activity on seasonal influenza mRNA vaccine

Two-step screening of lipid-polymer nanoparticles for efficient mRNA vaccine delivery and cancer immunotherapy

Zn-LNP coordinated nanoassembly-based mRNA vaccines for synergistic spleen-targeted delivery and potent tumor suppression via immunoprophylaxis and immunotherapy

Although cutaneous melanoma accounts for only about 2% of skin cancers, its rapid progression makes it an aggressive skin cancer with a high mortality rate. As of 2018, the SEER database estimated that the 5-year overall survival (OS) rate is 29.8% in patients with stage IV disease at diagnosis in the United States. Non-cutaneous melanoma, including mucosal and uveal subtypes, carries a generally worse prognosis. Once considered refractory to conventional treatments, such as chemotherapy and radiation therapy, the advent of immunotherapy, including immune checkpoint inhibitors (ICIs), vaccines, and tumor-infiltrating lymphocytes (TIL), and of targeted therapy over the past decade has resulted in dramatic improvements in melanoma. Importantly, ICIs have resulted in long-term remission for patients with melanoma, thus introducing the possibility of a cure for some patients with metastatic disease. These include antibodies against programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and lymphocyte activation gene-3 (LAG-3). In this review, we will provide an overview of metastatic melanoma while focusing on its current pharmacologic armamentarium, toxicities of treatment, including ICIs and targeted therapy, and its therapeutic clinical strategies. The therapeutic advances presented in this review serve as the foundation for an ever-expanding repertoire of innovative approaches. These include mRNA vaccines, oncolytic viruses, bispecific engagers, oral immunomodulators, and novel cytokines. Adoptive cellular strategies are evolving to TILS transduced with conditional gene expression cassettes, as well as non-T cell approaches involving dendritic cells and natural killer (NK) cells. Targeted therapy strategies have broadened to include upstream components of RAS, other MAP kinase pathways, and HDAC inhibitors, among others. All these new paradigms translate into increasingly complex decision-making for the treatment team, a burden that is more than offset by the tremendous benefit for melanoma patients. This is truly the beginning of a new era.

SARS-CoV-2 fusion-peptide-directed antibodies are elicited by natural infection and can mediate broad sarbecovirus neutralization.

Direct comparison of adverse events (AEs) and flares among the coronavirus disease 2019 (COVID-19) vaccine platforms in systemic lupus erythematosus (SLE) patients has rarely been determined. This study aimed to compare AEs and flares among 3 different COVID-19 vaccine platforms in SLE patients. Risk factors for SLE flares following vaccination were also determined. Adult SLE patients completing 2 doses of primary series COVID-19 vaccine (inactivated virus, adenovirus-vectored, and mRNA vaccines), were included in this study. The patients were followed up until 3 months after the 2nd vaccine dose or study censor. SLE disease activity and flares were determined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) and Safety of Estrogens in Lupus Erythematosus National Assessment – SLEDAI Flare Index, but the modified SLEDAI-2K score was used instead of the original SLEDAI-2K. Sixty-seven, 19, and 46 patients received inactivated virus, adenovirus-vectored, and mRNA vaccines, respectively. The incidence rate and 95% confidence interval (IR [95% CI])/100 patient-months was not different for overall AEs (38.2 [27.6–53.0], 44.2 [23.8–82.2], and 49.3 [35.7–68.0], respectively, P = .496) and flares (10.4 [6.1–17.5], 14.6 [6.1–35.2], and 7.1 [3.8–13.3], respectively, P = .561). Severe flares were more common than mild-to-moderate ones, primarily due to renal flare, regardless of vaccine types. There was no significant change in SLE disease activity after vaccination across the vaccine types. High number of the 1997 American College of Rheumatology classification criteria and use of combination immunosuppressive drugs at 1st vaccine dose were independent risk factors for flares. There was no significant difference in overall AEs, changes in SLE disease activity, frequency, and severity of flares, regardless of the vaccine platforms.

Influenza A(H1N1) represents a paradigm of viral adaptability and persistent pandemic threat, having shaped public health responses and scientific understanding for over a century. This comprehensive interdisciplinary review synthesizes virological, epidemiological, clinical, and socio-political perspectives on H1N1, from the 1918 "Spanish Flu" pandemic to the contemporary circulation of A(H1N1)pdm09 as a seasonal pathogen. We examine the molecular mechanisms underpinning H1N1's evolutionary success, including its segmented genome facilitating antigenic shift and drift, and its sophisticated repertoire of accessory proteins that modulate host immunity. The review provides novel analyses of major pandemics, re-evaluating the 1918 pandemic through modern genomic archaeology and detailing the complex, decade-long evolutionary pathway that culminated in the 2009 pandemic strain. A significant focus is dedicated to case studies of national responses, with an in-depth examination of Egypt's controversial 2009 intervention—the mass culling of pigs—analyzed through the intersecting lenses of epidemiology, economics, social justice, and cultural politics. The review incorporates the latest scientific advances (2020-2024), including insights from the COVID-19 era on viral co-circulation, immunity debt, and mRNA vaccine platforms. We assess current vaccine effectiveness, antiviral resistance patterns, and the promising development of universal influenza vaccines. Furthermore, the review critically addresses persistent challenges in global health equity, preparedness governance, and the implementation of a truly integrated "One Health" approach. By integrating 100 contemporary references, this work argues that H1N1 is not merely a seasonal nuisance but a persistent biosocial phenomenon that reveals the intricate connections between viral evolution, animal reservoirs, human societies, and public health infrastructure. The review concludes that future mitigation requires sustained investment in equitable surveillance, next-generation countermeasures, and strategies that address the socio-economic determinants of outbreak impact, providing a roadmap for confronting both seasonal influenza and the next inevitable pandemic.

HIV/SIV-specific CD8+ T cell responses are typically unable to control viral rebound following antiretroviral therapy (ART) interruption (ATI). To investigate whether enhancing the magnitude and activation of SIV-specific CD8+ T cells at the time of ATI can improve the immune interception of reactivating SIV infections we vaccinated SIVmac239-infected rhesus macaques (RMs) on ART, boosting immediately prior to ATI, with a nucleoside-unmodified mRNA vaccine expressing SIVmac239 Gag (mRNA/SIVgag) alone or in combination with Nef (mRNA/SIVnef) and Pol (mRNA/SIVpol). The mRNA/SIVgag vaccine was effective in boosting Gag-specific CD8+ T cells in blood and lymphoid tissues. Following ATI, the mRNA/SIV-Gag vaccine group showed a significant delay in time to measurable viral rebound compared to controls, and manifested lower plasma viral loads (PVL) for up to 6 weeks after rebound. Similarly, RMs that received mRNA/SIVgag, mRNA/SIVnef, and mRNA/SIVpol also manifested a delay in SIV rebound compared to controls, suggesting that boosting SIV-specific CD8+ T cells during ATI can enhance early immune targeting of reactivating SIV infections. However, viral control was not sustained long-term as PVLs were similar across vaccinees and controls by 24 weeks post-rebound, highlighting the need for adjunctive therapies to improve the durability of virologic control elicited by CD8+ T cell-targeting vaccines.

In 2022, Australia saw an unprecedented outbreak of Japanese encephalitis virus genotype IV (JEV GIV). The outbreak involved 42 human cases with 7 fatalities, as well as affecting >80 pig farms in New South Wales and Queensland. Herein, we designed, constructed, and tested two JEV GIV mRNA vaccines encoding prME, which provided protection against a lethal JEV GIV challenge in an Ifnar-/- mouse model. The vaccines were not codon optimized and included either the Native (full-length) or a Shorter signal peptide, with the latter missing the N-terminal n-region. Two vaccinations with 5 µg of the Shorter vaccine provided neutralizing antibody responses that were significantly lower but overlapped with those seen after vaccination with Imojev, a live attenuated vaccine approved for use in humans. Both mRNA vaccines provided approximately a five to six log reduction in viremia, ≥80% protection against overt disease and weight loss, and mortality. The paper illustrates in-country mRNA vaccine generation in response to a local outbreak, with JEV mRNA vaccines potentially emerging to be easier to manufacture, cheaper, and more suitable for immunocompromised individuals.

Highly Efficient and Durable Th1-Biased Protective Immunity Induced by a Novel mRNA-LNP Vaccine Against RSV via AI-Assisted Antigen Screening.

Lipid nanoparticles (LNPs) have become the leading platform for mRNA delivery, exemplified by the success of mRNA vaccines. However, LNPs composed of classical lipid materials are still constrained by intrinsic hepatotropism and suboptimal intracellular delivery, restricting their broader clinical utility. To overcome these challenges, researchers are developing unconventional lipids, a class of next-generation lipid materials that are rationally engineered to enhance endosomal escape, confer programmable tissue selectivity, and reduce immunogenicity. In this Special Report, we highlight representative classes of unconventional lipids and discuss their impacts on in vivo mRNA delivery performance. Collectively, these next-generation materials are redefining LNPs from passive carriers into regulatable delivery systems capable of improving delivery efficiency, modulating biodistribution, and enhancing safety profiles. Such innovations are poised to expand the therapeutic reach of mRNA medicines across a wide range of diseases. [PubMed and Web of Science databases were searched for relevant articles published from January 2010 to December 2025].