Assessing the long-term efficacy of MPXV vaccine candidates is crucial for the global response to the ongoing mpox epidemic. Built upon our previous study of the mpox quadrivalent mRNA vaccine, herein we reported that MPXV-1103 could elicit sustained humoral and cellular immunity in mice, including the induction of MPXV A35/B6/A29/M1-specific IgG antibodies, VACV neutralizing antibodies and activated cytotoxic CD8+T cells, which provides 100% protection against lethal VACV challenge even at 280 days after the first vaccination. Our results provide critical insights for orthopoxvirus vaccine development.

Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated.
TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection.
TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy.
Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

A new generation of mucosal vaccine against the ever-evolving SARS-CoV-2 is of great value to fight COVID-19. In previous studies, our groups developed a viral vector vaccine based on an avirulent Newcastle disease virus (NDV) expressing the prefusion-stabilized spike protein of SARS-CoV-2 (NDV-HXP-S).
Here we characterized the in vivo biodistribution and immunogenicity of a live mucosal NDV-HXP-S vaccine in animal models.
NDV showed restricted replication in mice and hamsters. Despite limited replication, intranasal live NDV-HXP-S provided protection against SARS-CoV-2 challenge and direct-contact transmission in hamsters. Importantly, a trivalent live NDV-HXP-S vaccine (Wuhan, Beta, Delta) induced more cross-reactive antibody responses against the phylogenetically distant Omicron variant than the ancestral vaccine. Furthermore, intranasal trivalent live NDV-HXP-S boosted systemic and mucosal immunity in mice pre-immunized with mRNA vaccine.
Overall, a mucosal multivalent live NDV-HXP-S vaccine shows great promise as a safe, next-generation vaccine conferring broad mucosal and systemic immunity against future SARS-CoV-2 variants.
Copyright © 2025 González-Domínguez, Abdeljawad, Lai, Boza, McCroskery, Lemus, Slamanig, Singh, Warang, Yellin, Abbad, Carreño, Dolange, Martínez-Guevara, Singh, Barcena-Varela, Chang, Schotsaert, Krammer, Palese and Sun.

Here, we present a protocol for guiding tissue preparation and flow cytometric analysis in subcutaneous murine tumor models and secondary lymphoid organs. We describe steps for dissociating tumors, spleens, and lymph nodes to obtain single-cell suspensions. We then detail procedures for immune cell staining and analysis and gating strategies including the use of fluorescence-minus-one controls (FMOs). This approach provides valuable insights into the impact of cancer therapies on the tumor and systemic immune response. For complete details on the use and execution of this protocol, please refer to Ingelshed et al.1.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Clinical approaches for cancer therapy face several interrelated challenges involving inefficient drug delivery, potential adverse side effects, and inconvenience. Here, we present an integrated wearable flexible ultrasound microneedle patch (wf-UMP) that serves as a portable platform for convenient, efficient, and minimally invasive cancer therapy. The wf-UMP adopts an all-in-one bioelectronic concept, which integrates a stretchable lead-free ultrasound transducer array for acoustic emission, a bioadhesive hydrogel elastomer for robust adhesion and acoustic coupling, and a dissolvable microneedle patch loaded with biocompatible piezoelectric nanoparticles for painless drug delivery and reactive oxygen species generation. With soft mechanical properties and enhanced electromechanical performance, wf-UMP can be robustly worn on curved and dynamic tissue surfaces for easy and effective manipulation. In preclinical studies involving mice, wf-UMP demonstrated notable anticancer effects by inducing tumor cell apoptosis, amplifying oxidative stress, and modulating immune cell proliferation. Furthermore, the synergistic immunotherapy induced by wf-UMP and Anti-PD1 further improved anticancer immunity by activating immunogenic cell death and regulating macrophages polarization, inhibiting distant tumor growth and tumor recurrence.
© 2025. The Author(s).