Background LC16m8 is a live-attenuated, replication-competent vaccinia vaccine, but clinical evidence on its efficacy against mpox remains limited. We assessed its efficacy and safety in adults at increased risk of mpox in Colombia. Methods We conducted a hybrid study comprising a multicentre, open-label, randomised delayed-vaccination trial and an observational cohort at three centres in Bogotá. Adults aged 18–50 years were randomised 1:1 using stratified permuted blocks to receive one percutaneous dose of LC16m8 at enrolment (Day 0) or on Day 42. The primary outcome was PCR-confirmed mpox during the arm-specific efficacy-assessment windows, analysed in the per-protocol efficacy population; no efficacy outcomes were imputed. Safety outcomes were assessed through Day 180. ClinicalTrials.gov NCT06223919; retrospectively registered; trial closed to recruitment. Findings Between December 16, 2023, and January 6, 2024, 208 participants were enrolled and 204 randomised (104 immediate; 100 delayed); 203 were male and one female. The trial randomised 204 of 8686 planned participants. No PCR-confirmed mpox cases occurred in the primary per-protocol efficacy analysis (0/97 immediate vs 0/69 delayed); therefore, the prespecified hazard ratio, 95% CI, p value, and vaccine efficacy were not estimable. Through Day 180, at least one adverse event was reported by 96/98 (98·0%) participants in the immediate-vaccination group and 68/69 (98·6%) in the delayed-vaccination group. One serious adverse event occurred in each group; both were unrelated to vaccination and resolved. No deaths or adverse-event-related study discontinuations occurred. Interpretation Substantial under-recruitment and the absence of primary outcome events precluded estimation of LC16m8 efficacy. The randomised safety findings were limited by the small sample size. Funding Japan Agency for Medical Research and Development (AMED; JP22fk0108503h0001); Ministry of Health and Social Protection of Colombia; Universidad Nacional de Colombia; National Institute of Health of Colombia.
Background Computed tomography (CT) stages pancreatic ductal adenocarcinoma (PDAC) but does not read out the treatment-guiding tumour biology, requiring biopsy. Whether an imaging-biology relationship discovered in preclinical MRI holds independently in human CT is unknown. Methods One pipeline was applied to two PDAC cohorts: longitudinal 9.4 T multi-parametric MRI (169 sessions; 1002 image series, 471 quantitative maps) with terminal histopathology in male C57BL/6 mice bearing orthotopic KPC-derived tumours treated with gemcitabine, a dendritic-cell vaccine, both, or neither, and abdominal CT with matched proteogenomics from CPTAC-PDA. Radiomics and frozen foundation-model embeddings were modelled under grouped cross-validation against five pre-specified paired endpoints, with no cross-species transfer of features, weights, or labels. Findings Applied independently, the pipeline recovered four matched molecular endpoints in both species (CD8 infiltration, stromal collagen, CD8:CD68 immune balance, cytolytic activity), with areas under the receiver-operating-characteristic curve (AUROCs) of 0.938–0.960 in mice and 0.780–0.856 in humans. Survival concordance indices were 0.729 and 0.689. After adjustment for age, stage, and grade, the human imaging score remained independently prognostic (hazard ratio 1.87 per SD, 95% CI 1.32 to 2.66; p < 0.001 [Wald test]; combined concordance index 0.726 versus 0.611 for clinical covariates). Findings held in portal-venous-restricted analysis; frozen embeddings outperformed end-to-end fine-tuning in both arms. Interpretation One pipeline recovered matched PDAC biology in mouse MRI and human CT, supporting preclinical imaging to nominate non-invasive CT biomarker candidates for biopsy-sparing PDAC trial stratification, pending prospective external validation. Funding National Cancer Institute; Society of Interventional Radiology Foundation; University of California Irvine Anticancer Challenge Pilot grant.
Background Oropouche virus (OROV) is an emerging orthobunyavirus responsible for widespread febrile illness across the Americas, with recent epidemiological modelling estimating over 9.4 million infections between 1960 and 2025. The virus underwent unprecedented geographic expansion during 2023–2024, leading to imported cases in non-endemic regions worldwide. Currently, no licenced vaccine is available, and most vaccine development efforts rely on the historical prototype strain BeAn19991. However, the antigenic properties of the OROV glycoprotein complex remain incompletely defined, hindering rational vaccine design. Methods We generated OROV pseudovirions expressing the Gn and Gc glycoprotein complex (GPC) using a vesicular stomatitis virus (VSV)-based system. A robust in vitro neutralisation assay was established to quantify neutralising antibody titres against these pseudovirus. Representative strains from historical lineages and contemporary circulating variants (2022–2024) were systematically characterised through phylogenetic analysis and cross-neutralisation assays using female guinea pig sera. Findings Phylogenetic analysis of the OROV GPC identified four distinct genetic clades: clade I (Brazilian strains isolated between 1960 and 2006), clade II (Ecuador 2016 and Peru 2024 isolates), clade IIIa (Brazilian strains from 2009 to 2018), and clade IIIb (epidemic strains circulating during 2022–2024). While all representative strains elicited comparable homologous neutralisation titres, significant antigenic divergence was observed among heterologous strains. Sera induced by the prototype strain BeAn19991(belonging to Clade Ⅰ) exhibited markedly reduced neutralising activity (>4-fold reduction) against heterologous OROV strains and provided limited protection against clade IIIb circulating variants. In contrast, sera induced by AJT39490, which belongs to Clade IIIa, demonstrated broad-spectrum cross-neutralising activity against all tested OROV strains, highlighting its cross-protective potential as a candidate antigen with broad cross-neutralising capability. Interpretation This study provides a systematic characterisation of OROV glycoprotein antigenicity using a pseudotyped virus platform. Our findings demonstrate substantial antigenic diversity among OROV strains, revealing that the historical prototype strain BeAn19991 may not provide sufficient protection against contemporary circulating variants. Notably, the broad cross-neutralisation capacity exhibited by AJT39490-induced sera highlights its potential as a candidate antigen for inducing protective immunity against diverse OROV lineages, addressing a critical gap in current OROV vaccine development efforts. Funding Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project (2025ZD01900600)
