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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 ( P  = 3.2 × 10 −9 ), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42–0.93, P  = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation. Variation in antibody levels elicited by the COVID-19 vaccine ChAdOx1 nCov-19 is linked to specific major histocompatibility complex class II alleles, providing insight into the breadth of immune response among vaccinated individuals.

Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV + male participants on antiretroviral therapy (undetectable viral loads, CD4 + T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4–6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.

Paediatric COVID-19 vaccination programmes were initiated in response to the coronavirus pandemic declared by the World Health Organisation (WHO) in 2020. Ten COVID-19 vaccines received WHO Emergency Use Listing, however, only five were approved for use in children. ChAdOx1 nCoV-19 (AZD1222) was approved in adults in a two-dose regimen. We previously reported interim findings of a phase 2 study of ChAdOx1 nCoV-19 in children with immunogenicity, comparable with adults. Final results after 12 month follow-up are reported. Single-blind, randomised controlled trial across four UK centres, recruiting 261 children and adolescents (aged 6-17 years). Participants received either two doses of ChAdOx1 nCoV-19 or Bexsero vaccine (controls). The primary outcome was safety (adverse events for 28 days following vaccination and serious adverse events throughout), and secondary outcome was immunogenicity (measured by SARS-CoV-2 anti-spike enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot (ELISpot)). Five serious adverse events and four adverse events of special interest were reported. None were related to study vaccinations, and there were no deaths. Geometric mean titres (GMTs) from an anti-spike (Wuhan) ELISA in participants aged 6-11 years were 1 EU/ml (95% CI 1-2) at baseline versus 796 EU (95% CI 161-3948, n =4) at D364. In participants aged 12-17 years, GMTs were 1 EU/ml (95% CI 1-2, n=3) at baseline versus 1432 EU/ml (95% CI 2337-6083; n=6) at D364 (2 dose regimen at 112-day interval), compared to 3 EU/ml (95% CI 0-62) at baseline versus 392 EU/ml (95% CI 24, 6493; n=3) at D364 (2 dose regimen at a 28-day interval). A two-dose regimen of ChAdOx1 nCoV-19 was immunogenic and safe in the trial population. No vaccine-related serious adverse events were reported. Immune responses persisted to 12 months in participants who did not experience breakthrough infection, This trial was registered with ISRCTN, trial number 15638344. The study was funded by the Department of Health and Social Care, through the National Institute for Health Research, and AstraZeneca.

Early in vivo dynamics of human immune-cell activation across regionally activated lymphoid tissue sites upon immunisation are poorly characterised in ancestrally diverse individuals. Here, we profiled draining and non-draining axillary lymph nodes (dLNs and ndLNs) by ultrasound-guided fine-needle aspiration (FNA) in 13 Black and Asian ancestry individuals, before and 3-7 days after vaccination with adjuvanted influenza vaccine. Draining but not ndLNs rapidly increased in size post-vaccination, by day 3, with distinct cellular dynamics determined through single cell multiomics. Dissecting LN cellular diversity into 42 lymphoid and non-lymphoid cell states, post-vaccination cell abundance changes were observed across all LNs, but dLNs were specifically characterised by CD4+ T follicular helper (CD4+ Tfh) cell expansion. Gene expression analysis revealed a dLN post-vaccination hub of multicellular activity defined by CD4+ Tfh signalling, cross-compartmental activation, translation, and enhanced antigen-presentation capacity. Thus, robust responses to intramuscular immunisation transcending ancestral inter-individual variation are elicited through temporal, anatomical and cellular lymphatic co-ordination with implications for vaccine design in ancestrally diverse populations. In this study of ancestrally diverse young adults, the temporarily co-ordinated response to an adjuvanted influenza vaccine at lymph nodes local to (draining) and distal from (non-draining) the injection site, reveals early regulation of cellular kinetics and anatomical hierarchy of the innate and adaptive immune responses.

Alzheimer’s disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis of astrocytes in APP/PS1 ß-amyloidopathy and MAPT P301S tauopathy mice revealed that only Aß influenced expression of AD risk genes, but both pathologies precociously induced age-dependent changes, and had distinct but overlapping signatures found in human post-mortem AD astrocytes. Both Aß and Tau pathology induced an astrocyte signature involving repression of bioenergetic and translation machinery, and induction of inflammation pathways plus protein degradation/proteostasis genes, the latter enriched in targets of inflammatory mediator Spi1 and stress-activated cytoprotective Nrf2. Astrocyte-specific Nrf2 expression induced a reactive phenotype which recapitulated elements of this proteostasis signature, reduced Aß deposition and phospho-tau accumulation in their respective models, and rescued brain-wide transcriptional deregulation, cellular pathology, neurodegeneration and behavioural/cognitive deficits. Thus, Aß and Tau induce overlapping astrocyte profiles associated with both deleterious and adaptive-protective signals, the latter of which can slow patho-progression. Alzheimer’s disease is associated with changes in astrocytes. Here the authors investigated the astrocyte translatome associated with amyloid-ß and tau pathology.

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing and protective equipment; pharmaceutical interventions, including vaccination; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. Implemented in pure Python, Covasim has been designed with equal emphasis on performance, ease of use, and flexibility: realistic and highly customized scenarios can be run on a standard laptop in under a minute. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine epidemic dynamics and inform policy decisions in more than a dozen countries in Africa, Asia-Pacific, Europe, and North America.

Vision-based grasping for mobile manipulators poses significant challenges in machine perception, computational efficiency, and real-world deployment. This study presents a computationally lightweight, end-to-end grasp detection framework that integrates object detection, object pose estimation, and grasp point prediction for a mobile manipulator equipped with a parallel gripper. A transformation model is developed to map coordinates from the image frame to the robot frame, enabling accurate manipulation. To evaluate system performance, a benchmark and a dataset tailored to pick-and-pack grocery tasks are introduced. Experimental validation demonstrates an average execution time of under 5 s on an edge device, achieving a 100% success rate on Level 1 and 96% on Level 2 of the benchmark. Additionally, the system achieves an average compute-to-speed ratio of 0.0130, highlighting its energy efficiency. The proposed framework offers a practical, robust, and efficient solution for lightweight robotic applications in real-world environments.

Transfer of patient care from an intensive care unit (ICU) to a hospital ward is often challenging, high risk and inefficient. We assessed patient and provider perspectives on barriers and facilitators to high-quality transfers and recommendations to improve the transfer process. We conducted semistructured interviews of participants from a multicentre prospective cohort study of ICU transfers conducted at 10 hospitals across Canada. We purposively sampled 1 patient, 1 family member of a patient, 1 ICU provider, and 1 ward provider at each of the 8 English-speaking sites. Qualitative content analysis was used to derive themes, subthemes and recommendations. The 35 participants described 3 interrelated, overarching themes perceived as barriers or facilitators to high-quality patient transfers: resource availability, communication and institutional culture. Common recommendations suggested to improve ICU transfers included implementing standardized communication tools that streamline provider–provider and provider–patient communication, using multimodal communication to facilitate timely, accurate, durable and mutually reinforcing information transfer; and developing procedures to manage delays in transfer to ensure continuity of care for patients in the ICU waiting for a hospital ward bed. Patient and provider perspectives attribute breakdown of ICU-to-ward transfers of care to resource availability, communication and institutional culture. Patients and providers recommend standardized, multimodal communication and transfer procedures to improve quality of care.

To test the feasibility of sleep hygiene education and longitudinal wrist actigraph sleep metrics measurement alone versus in combination with telehealth-delivered cognitive behavioral therapy for insomnia (teleCBT-I) for people with prostate cancer (PC) receiving androgen deprivation therapy (ADT). 45 men with PC receiving ADT were recruited from a midwestern comprehensive cancer center. Participants were provided with wrist actigraphs, their individual sleep metrics data, and sleep hygiene education. Half the sample was randomized to a four-week teleCBT-I intervention. Outcomes were collected at baseline, one month, and two months. Exit interviews were conducted to glean participants' feedback about the study. Feasibility was demonstrated. Physical function, sleep efficiency, fatigue, and health-related quality of life improved for participants receiving teleCBT-I. Assessment of sleep disturbance, access to sleep hygiene education, and teleCBT-I may benefit people with PC receiving ADT.

Mobile manipulators have become essential platforms for autonomous tasks that demand high-quality performance and efficient operational processes. This paper presents a complete grocery pick-and-pack system for a mobile manipulator, integrating a graphical user interface (GUI) with an end-to-end vision-based grasp detection pipeline designed for lightweight computation. The system is evaluated on the Grocery Pick-and-Pack Benchmark (Level-3), the most challenging level due to deformable objects, dimensional constraints, and strict grasp-point requirements. Experimental results demonstrate an average success rate of 92% across five item classes, with the deformable sweet bag the most challenging at 60% and an average execution time of 7.5 s on an edge device. The system achieves strong computational efficiency, reflected by a compute-to-speed ratio (CSR) of 0.008, with a total model size of only 30.9 MB. Performance is further validated across multiple hardware platforms and under real competition scenarios in the European Robotics League 2025. The findings highlight the practical impact of lightweight, vision-based mobile manipulation and provide insights into current challenges and future research directions for autonomous robotic applications.