Recent years have seen a growing interest in embodied urban political ecology. In this article we offer a generative methodological intervention into the field: engagement with a form of experimental mapping we call experiential cartography. This approach incorporates not only tangible data but also engages the senses, feelings, emotions, and perceptions, offering a richer and more nuanced way of understanding and visualizing the world. To present experiential cartography's potential contributions to UPE research we draw on some recent research in the Philippines emerging from our Embodied Ecologies project that has sought to study and intervene in how people sense, know, and act on the cumulative toxicities that permeate everyday urbanized life. Experiential cartographies of cumulative toxicities offer an interesting case for UPE to explore situated experiences and everyday embodiments of planetary urbanization. We organize our examples around Henri Lefebvre's triadic theoretical formulation of the production of space to argue that experiential cartography involves mapping embodied perceptions of spatial practice, creating embodied conceptions and representations of space, and cultivating embodied spaces of representation based on lived experiences. In this way, experiential cartography provides a methodology for not only (academically) analyzing but also (collectively) intervening into the production of urban spaces and ecologies. We suggest experiential cartography is one way that UPE scholars may pay greater attention to embodied activities, experiences, and knowledges. As the intentions of this article are methodological, we lay out some concrete foundations for UPE scholars (or others) who may be interested in their own experiential mapping practices.
This article explores the uses of historical cartography in the territorial dispute between the states of Piauí and Ceará in a civil suit (1.831/2011) filed in Brazil's Supreme Court. We base our analysis on historical maps from the seventeenth to the nineteenth centuries in order to understand continuities and transformations in how this region is represented. This analysis is then contrasted with documentation from the Overseas Historical Archive and the Brazilian Army's Technical Report on the dispute in order to relate the active role played by the environment, political influences with representations of the zones involved in the dispute, showing how cartography still serves to "reflect the world." Este artigo explora os usos da cartografia histórica na disputa territorial entre Piauí e Ceará, ajuizada em ação cível originária n.1.831/2011 no Supremo Tribunal Federal. Propomos um exercício analítico a partir de mapas históricos dos séculos XVII a XIX, no intento de perceber as continuidades e transformações nos modos de representar a região. Contrastamos esse exercício com documentação do Arquivo Histórico Ultramarino e com o Relatório Técnico do Exército Brasileiro sobre a disputa. Com isso, buscamos relacionar a agência do ambiente, influências políticas e representações das zonas litigantes, demonstrando como a cartografia permanece utilizada como “espelho do mundo”.
This study aimed to analytically map functional knee phenotypes (FKP) to the Coronal Plane Alignment of the Knee (CPAK) classification, evaluate CPAK's ability to represent native coronal alignment variability in non-osteoarthritic (NO) and osteoarthritic (OA) populations and propose a simplified translational framework between both systems. It was hypothesized that CPAK represents a discretized form of native coronal alignment and that its relationship with functional phenotypes is inherently probabilistic. Arithmetic hip-knee-ankle angle and joint line obliquity were analytically derived from femoral and tibial mechanical angles, enabling direct conversion of functional phenotypes into CPAK types. A theoretical cartography was constructed using mean values and full angular intervals (±1.5°). Four assignment strategies were applied: deterministic assignment, interval propagation, stochastic Monte Carlo simulation and least probable CPAK scenario. Conversions were performed in 308 NO and 2692 OA knees from the functional phenotype cohort and compared with 500 NO and 507 OA knees from the CPAK cohort. A synthetic bidimensional framework (Hirschmann-CPAK Translational grid [HCT-9]) was analytically derived. Considering angular intervals, each functional phenotype corresponded to multiple CPAK types (mean 1.7 per phenotype), showing that deterministic conversion underestimated variability. In NO knees, distributions obtained using the mean, interval, stochastic and rare methods differed significantly from the original cohort (all p < 0.001). In OA knees, the distribution obtained using stochastic conversion showed no significant difference (p = 0.188), suggesting probabilistic convergence. Extreme types were overrepresented in the rare scenario. The HCT-9 framework identified zones of low and high ambiguity, particularly in central phenotypic regions. The relationship between FKP and CPAK is inherently probabilistic. The HCT-9 framework enables structured translation between both systems and supports a shared alignment language for total knee arthroplasty. Level III, comparative retrospective study.
Min, Schweizer, and colleagues use artificial intelligence-powered deep visual proteomics to generate a spatial proteomic atlas of pancreatic cancer precursor evolution, revealing that major metabolic and inflammatory reprogramming occurs long before overt histologic transformation. More broadly, the study highlights the emerging potential of spatial proteomics and multiomics to bridge histopathology with molecular pathology and precision oncology. See related article by Min et al., p. 1323.
The ongoing evolution of SARS-CoV-2, particularly the emergence and rapid spread of new immune-evasive variants, continues to challenge the durability of vaccine-induced protection. Understanding how repeated variant exposures shape neutralizing antibody breadth is therefore essential for optimizing booster design. Here, we investigated polyclonal neutralizing antibody responses in individuals who received a bivalent (ancestral + BA.4/5) boost followed by an additional monovalent XBB.1.5 boost, with and without breakthrough infection, against a diverse panel of SARS-CoV-2 variants. To visualize human multi-exposure immunity in antigenic space via antibody landscapes, we extended our existing human sera-based antigenic map with hamster sera infected with more recent variants. The hamster sera allowed us to map BA.2.86 and JN.1 variants, which largely escape human single exposure sera. Our analysis of human multi-exposure sera revealed that the number and type of exposures significantly shaped antibody landscapes. The XBB.1.5 booster immunization notably increased neutralizing antibody titers across variants, elevating the height of the antibody landscape. However, titers against more recent Omicron variants, such as JN.1, were low despite booster administration. These findings highlight the dynamic nature of SARS-CoV-2 immunity and emphasize the need for continuous monitoring and adaptation of vaccine strategies to maintain effective protection against emerging variants.
Rheumatoid arthritis (RA) is not a uniform inflammatory pannus. It is a spatially organized, stage-dependent synovial immune ecosystem. Cellular cartography resolves synovitis into lymphoid, myeloid, stromal, and neuroimmune niches that track erosive disease, fibroproliferation, and pain-dominant states. Ecosystem state can differ between joints and shift over time, explaining a key paradox: inflammation may fall while relapse risk or pain persists. Longitudinally, RA evolves from preclinical immune dysregulation with mucosal priming to joint niche consolidation, then to refractory states reinforced by inflammatory memory, stromal imprinting, and neuroimmune sensitization. This argues for biomarkers that report dominant niche drivers and memory programs, not only inflammatory load. Therapies should be phase-matched and niche-targeted, combining stromal or neuroimmune modulation with immune-reset platforms such as T-cell engagers and CAR-T.
Hematopoietic stem and progenitor cells (HSPCs) respond to infections, inflammation, and regenerative challenges using emergency myelopoiesis (EM) pathways to amplify myeloid cell production. However, it remains unclear how various EM inducers regulate HSPCs using shared or distinct molecular mechanisms. Here, we generate a comprehensive and generalizable cell annotation method (HemaScribe) and a refined quantitative model of hematopoietic differentiation (HemaScape) using single-cell RNA sequencing (scRNA-seq) of murine HSPCs, which we apply to a broad range of EM modalities. We uncover multiple strategies for enhancing myelopoiesis that act at different levels of the HSPC hierarchy and are associated with both unique and shared transcriptional response modules. In particular, we identify a myeloid progenitor-based EM activation module across diverse inflammatory challenges that is conserved in humans and informs outcomes in adult and pediatric acute myeloid leukemia. Our work illuminates fundamental regulatory mechanisms in hematopoietic regeneration that have direct translational applications in disease contexts.
Myoepithelial cells (MECs) are contractile cells that exhibit both epithelial and smooth muscle characteristics. In the salivary glands, they contribute to secretion and maintenance of glandular architecture and play a fundamental role in the development and differentiation of various neoplasms, both benign and malignant. Their involvement is particularly evident in tumors such as pleomorphic adenoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. However, identifying MECs in tumor tissues can be challenging due to their variable morphologies and phenotypic profiles. A comprehensive literature review was performed focusing on MECs and salivary gland tumors. Immunohistochemistry has become an essential tool for MEC detection, and commonly used markers include smooth muscle actin (α-SMA) and calponin, which demonstrate good sensitivity for the contractile phenotype. S100 protein and p63 are also frequently applied, though their specificity is limited when used individually. Additional markers such as cytokeratins, GFAP, and maspin may provide complementary information, particularly in combined panels. Accurate identification of MECs through immunohistochemical profiling is essential for proper tumor classification. Therefore, this review aimed to provide a summary of the immunohistochemical markers applied for the identification of MECs and highlights the relevance of these markers in the context of salivary gland neoplasms, emphasizing the combination of different markers, given the absence of a single marker with both high specificity and sensitivity.
This article examines how European consent systems for deceased organ donation are evolving, arguing that the focus on opt-in versus opt-out consent systems overshadows the governance structures determining how consent is obtained at the bedside. Through legal analysis, it shows that the impact of opt-out schemes-often described as presumed consent schemes-depends on the usability of organ donation registers, evidence of the deceased's wishes, family influence, and documentation accuracy. While opt-out regimes are widespread and often operationally 'soft' (family-centred at the bedside), they generate a number of issues from a human rights perspective. The article introduces a medico-legal taxonomy connecting legal default rules, the design of organ donor registers, and family decisions about donation, suggesting a practical model for 'soft harmonisation' that respects national constitutional choices. Central to this is a European Consent Status Summary and six governance pillars to improve transparency, interoperability, and traceability without forcing a single consent model. This approach aims to reduce litigation, support cross-border organ exchanges, and build public trust by ensuring that, wherever they exist, the deceased's recorded or reliably reconstructed wishes are identified and given primacy in the transplantation process, regardless of the applicable consent default.
In this issue of Cancer Cell, Alonso et al. demonstrate that in patients with advanced colorectal cancer, there are regionally distinct genomic and transcriptomic adaptive responses to KRAS G12C inhibition, including epithelial cell state changes and pro-inflammatory pathway enrichment, and provide insights into key resistance mechanisms to KRAS G12C inhibition.
Rapidly evolving viral variants pose challenges for developing vaccines for older adults (aged ≥60 years), who might respond poorly to new antigens because of pre-existing antibody repertoires imprinted by ancestral strains. Repeat infection with divergent GII.4 strains makes norovirus an ideal model for studying the effect of immune imprinting on vaccine neutralising antibody (NAb) responses. The aim of this study was to explore the magnitude, breadth, and durability of GII.4-NAbs in the context of population-based immune imprinting and virus evolution, to inform the design of future vaccines optimised for protection against norovirus variants. In this post-hoc analysis, we evaluated serum samples collected during a phase 2, randomised, controlled, double-blind trial (NOR-204; NCT02661490) conducted at ten centres in the USA evaluating the safety and immunogenicity of a GI.1/GII.4c bivalent virus-like particle norovirus vaccine candidate in healthy adults aged 60 years or older. In this study, we included participants from the NOR-204 trial who had received a single unadjuvanted dose of vaccine, had provided consent for future sample use, were aged 60-74 years and 85 years or older, and for whom sufficient serum volume was available; participants aged 75-84 years were excluded. NAb titre to GII.4 variants (ancestral variants: US95/96, FH2002, and YE2006a; contemporary variants: DH2006b, NO2009, SY2012, SF2017, AL2018, and WI2021) was measured using a surrogate assay in serum collected at days 1 (baseline), 57 (28 days after vaccination), and 393 (365 days after vaccination) to compare the magnitude, breadth, and durability of NAbs. Antigenic relationships among GII.4 variants were visualised by antigenic cartography. Participants were enrolled in the NOR-204 trial between Feb 1, 2016, and Oct 31, 2017. In this study, we included 45 (59%) of 76 participants who received a single unadjuvanted dose of vaccine in the NOR-204 trial; we excluded 25 (100%) of 25 participants aged 75-84 years and included 23 (92%) of 25 participants aged 60-74 years and 22 (85%) of 26 participants aged 85 years or more. 26 (58%) of 45 participants were female and 19 (42%) were male; 41 (91%) participants were White, three (7%) were Asian, and one (2%) was Black or African American. Serum was available for analysis for all participants on days 1 and 57 (n=45) and for 44 participants on day 393. Before vaccination, GII.4 surrogate NAb (sNAb) geometric mean titres (GMTs) were the highest against ancestral variants and lowest against contemporary variants compared with those for US95/96 (p<0·05). On day 57, GII.4 sNAb GMTs were elevated against all the GII.4 variants tested compared with day 1 (p<0·0001), although only GII.4c and DH2006b sNAb titres were as high as the titres of ancestral GII.4 variants (p>0·05, compared with US95/96). At day 393, GII.4 sNAb GMTs were lower than those at day 57, but all ancestral variants, GII.4c, DH2006b, and AL2018 had GMTs higher than those at day 1 (p<0·05); only GII.4c GMT remained as elevated as GMTs targeting ancestral variants (p>0·05, compared with US95/96). Antigenic cartography was used to visualise serum samples cross-reactivity patterns. GII.4 variants that circulated until 2006 (CW1987, US95/96, FH2002, YE2006a, and DH2006b) and GII.4c formed antigenic cluster 1, whereas GII.4 variants that emerged between 2009 and 2021 (NO2009, SY2012, SF2017, AL2018, and WI2021) formed antigenic cluster 2 before vaccination. At days 57 and 393, contemporary variants were further resolved into two subclusters, 2A (DH2006b, SY2012, and AL2018) and 2B (NO2009, WI2021, and SF2017). Analyses support the hypothesis that a vaccine composed of ancestral variant NAb sites boosts sNAb titre imprinted from natural exposures, driving magnitude, breadth, and durability in older adults. Optimal vaccination strategies could combine an ancestral variant able to capitalise on imprinted NAbs to recall breadth and magnitude, and a divergent variant to expand durability to distant contemporary viruses. National Institute of Allergy and Infectious Diseases, HilleVax.
Seasonal influenza causes significant morbidity and mortality annually. In 2025, the genetically divergent A/H3N2 K subclade (J.2.4.1) emerged with substantial haemagglutinin mutations. However, despite suggested antigenic escape, UK vaccine effectiveness estimates and epidemiological data demonstrated a relatively normal influenza season across 2025-26. We examined neutralising antibody responses in human cohorts to investigate existing and vaccine-induced immunity to K clade viruses. We characterised the antigenic relationships of a selection of A/H3N2 viruses spanning recent evolution including a subclade K virus using antigenic cartography, followed by serological antibody profiling of four human cohorts from the United Kingdom and Norway using microneutralisation (MN) and haemagglutination inhibition (HAI) assays. Antigenic cartography from single-infection ferret antisera suggests significant antigenic drift from the vaccine strains. MN and HAI titres from 243 individuals across 4 human cohorts (ages 1-105 years) were measured for comparison. The 2025/26 Northern Hemisphere seasonal inactivated egg-derived trivalent influenza vaccine (eTIV, with J.2 A/H3N2) significantly boosted MN and HAI titres against all A/H3N2 viruses tested, including a subclade K virus (p < 0.001). Furthermore, serological profiles of cohorts stratified by age groups (≤5, >5-≤15, >20-≤25, >25-<60, and ≥60) showed pre-existing reactivity against the emergent subclade K viruses, with minimal inter-age variation, suggesting there was not an immunity gap within particular age groups. The 2025/26 seasonal inactivated eTIV vaccine effectively boosted neutralising titres despite substantial genetic and antigenic drift. Human serological profiling should be included in risk assessments and continued surveillance. The Francis Crick Institute with core funding from Cancer Research UK, UK Medical Research Council, and Wellcome Trust; UK Research and Innovation and UK Medical Research Council; National Institute for Health Research University College London Hospitals Biomedical Research Centre; UK Health Security Agency; Norwegian Institute of Public Health.
Since its emergence in 1996, the H5 avian influenza virus (AIV) A/Goose/Guangdong/1/1996 (Gs/GD) hemagglutinin (HA) has evolved into over 30 genetically and antigenically distinct clades, including the widespread clade 2.3.4.4b. Vaccination is widely used in endemic regions to reduce poultry losses and zoonotic risk. However, the evolving antigenic diversity and global co-circulation of multiple clades challenge the protective efficacy of poultry vaccines with poor antigenic matching to field strains, resulting in immune escape and vaccine failure. This study aimed to improve vaccine seed selection by identifying HA epitopes contributing to inter-clade antigenic differences. Recombinant clade-representative viruses were generated using HA genes from circulating H5 AIVs via reverse genetics with A/Puerto Rico/8/1934 (PR8) internal and neuraminidase genes. Antigenic relationships were assessed using hemagglutination inhibition (HI) assays with homologous and heterologous chicken antisera. Antigenic cartography revealed a clear distinction of clade 2.3.4.4 from others and notable intra-clade diversity. Pairwise antigenic and genetic comparisons identified 48 putative antigenic residues. These were individually introduced into a candidate HA by site-directed mutagenesis, and antigenic influence was assessed by HI using sera raised against the non-mutated HA. Four residues R82K, A83T, T204I, and F229Y had significant antigenic effects, with three (R82K, T204I, and F229Y [H5 numbering]) being novel. These findings demonstrate that combining serology and in silico residue analysis can identify key antigenic determinants. This work highlights the need for precise antigenic matching in vaccine design and highlights the value of combining molecular and immunological tools to optimize vaccine seed selection against diverse and evolving H5 strains. The continued evolution of H5 avian influenza viruses (AIVs), particularly the Gs/GD lineage, poses major challenges for poultry disease control and zoonotic risk mitigation. Vaccine effectiveness is undermined by antigenic drift and the co-circulation of diverse clades, often leading to mismatches between vaccine and field strains. This study addresses the critical need to improve vaccine strain selection by identifying hemagglutinin (HA) residues driving antigenic variation across H5 clades. Using recombinant viruses, antigenic cartography, hemagglutination inhibition assays, and mutagenesis, we pinpointed 48 key residues, with four R82K, A83T, T204I, and F229Y having major antigenic effects, including three novel markers. These findings advance our understanding of H5 antigenic evolution and provide a framework for predicting vaccine performance. By integrating molecular and serological data, our work informs rational vaccine seed strain selection, contributing to more broadly protective vaccines and improved control of H5 AIV in poultry, while reducing the risk of zoonotic transmission.
Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have enabled atlas-scale cellular cartography, with consortium efforts now assembling millions of cells across diverse tissues, donors, and technologies to build comprehensive references for cell identify and disease mechanism, yet the scientific value of these atlases hinges on robust computational integration across heterogeneous data sources. Unlike pairwise batch correction, atlas-level integration must jointly reconcile heterogeneous and often hierarchically nested batch effects across many datasets whose cell-type compositions are highly imbalanced, all while preserving subtle biological variation and remaining computationally tractable at the scale of millions of cells. Existing approaches often prioritize either batch mixing or preservation of local biological structure, and most cannot natively accommodate spatial coordinates. Here we introduce PRIME (Projection-based Robust Integration via Manifold Embedding), an ensemble integration framework that combines random-projection-based consensus anchoring, graph-Laplacian correction, and optional spatial-neighborhood regularization. Across multiple random projections of the expression manifold, PRIME uses consensus voting to keep only cell pairs that repeatedly matched, reducing false anchors caused by projection-specific distortions. For ST, PRIME couples this expression-based anchor graph with a coordinate-derived spatial neighborhood graph in a unified graph-Laplacian objective with closed-form solution, enabling simultaneous cross-batch alignment and local spatial coherence. Based on extensive benchmarking spanning diverse datasets, we show that PRIME consistently outperforms state-of-the-art methods in both batch correction and biological conservation across scRNA-seq and ST integration scenarios and downstream tasks including trajectory inference, spatial-domain preservation, and perturbation-response analysis. Particularly, when integrating a human hematopoiesis benchmark spanning eight donors and approximately 33,000 cells, PRIME preserves biologically coherent developmental trajectories in human hematopoiesis. It also maintains cortical laminar architecture across dorsolateral prefrontal cortex sections in a ST dataset and recovers known drug-target relationships in a perturbation atlas of more than 1 million cells while suppressing batch-associated confounders. Together, these results establish PRIME as a versatile and scalable framework for atlas-level integration of scRNA-seq and ST across diverse biological applications.
The Influenza B virus (IBV), which accounts for nearly a quarter of annual global influenza-associated morbidity, represents a major human respiratory pathogen. Since late 2019, IBV transmission patterns have shifted markedly following the emergence of COVID-19, yet systematic studies on IBV prevalence before and after the pandemic remain limited. We conducted systematic surveillance of 66 IBV isolates collected from Guangzhou during 2022-2023. Phylogenetic analysis of HA/NA genes was complemented with evolutionary rate estimation, hemagglutination inhibition assays, antigenic cartography, and structural modeling of hemagglutinin variants. We revealed the distinct epidemic trends of IBVs in Southern China: clade V1A.3a.1/V1A.3a.2 co-circulated in 2022-2023 influenza season, while complete replacement of V1A.3a.1 by V1A.3a.2 in 2023-2024 season, which was driven by a 1.36-fold increase in the evolutionary rate of the HA gene (1.632 × 10-3, P < 0.05) post-NPIs. Spatially, discrete Bayesian phylogeographic analysis confirmed that Jiangxi Province acted as the core upstream hub of the nationwide transmission of V1A.3a.1, which persisted endemically from Jiangxi in 2020 to six adjacent provinces in 2021 before its final extinction in China. Notably, cross-reactive HI and quantitative antigenic cartography elucidated antigenic divergence between V1A.3a.1 and V1A.3a.2 subclades, and revealed that the complete displacement of V1A.3a.1 by V1A.3a.2 was mediated by the broadened antigenic recognition of 2023 V1A.3a.2 isolates. Structural modeling revealed L144P in the 150-loop may be the primary driver of antigenic divergence, inducing conformational rearrangement in residues 146-148. This study elucidates the unique evolutionary and epidemic patterns of IBV in the subtropical region of southern China after the relaxation of COVID-19 NPIs, deciphers the molecular mechanism of clade replacement and antigenic diversification of the Victoria lineage V1A.3a subclade, and validates the sustained effectiveness of the WHO 2022 influenza B vaccine strain update in southern China. Our findings fill the gap in systematic surveillance of IBV in subtropical sentinel regions, identify Guangzhou as a key monitoring site for IBV evolutionary dynamics, and provide critical molecular and antigenic evidence for the optimization of regional influenza surveillance systems and vaccine strain selection strategies.
As key regulators of mucosal immunity, innate lymphoid cells (ILCs) are involved in tissue homeostasis, inflammation, and repair. Studying ILCs within their native microenvironment remains challenging due to the low abundance of these tissue-resident immune cells. Here, we applied cyclic multiplex immunofluorescence, namely multiepitope ligand cartography (MELC), in a systemic IL-33-induced type 2 inflammation model to spatio-temporally characterize ILC phenotype and localization in mouse lungs. Niche analysis with all identified cell types resulted in four distinct niches and an expansion of a mixed B and Plasma cell (BPC)/blood endothelial cell (BEC) niche, while the niche predominated by blood endothelial cells decreased at IL-33 day 3. Spatial neighborhood and coenrichment analyses revealed ILC2 accumulation in myeloid-rich peri-lymphatic niches at early time points of IL-33-mediated inflammation. ILC2s were in direct contact with activated alveolar macrophages and lymphatics. While they expressed ICOS under homeostatic conditions, pronounced expression of MHCII at days 1 and 3 of IL-33 stimulation was observed. Unlike ILC2s, NK cells/ILC1s were coenriched near blood vessels, next to B cells and plasma cells. Our findings demonstrate the utility of spatial multiplex imaging for dissecting rare immune cell localization and phenotypes and uncover dynamic, tissue-specific remodeling of ILC niches during early type 2 inflammation.
Patient-reported outcome (PRO) measure development involves multiple language-intensive stages, including conceptual domain definition, candidate item generation, qualitative refinement, and cognitive interviewing prior to psychometric evaluation. Large language models (LLMs) may offer new opportunities to support these qualitative development activities, although their role within established PRO development frameworks remains incompletely defined. This commentary proposes a practical human-in-the-loop roadmap for integrating LLMs into the qualitative phases of PRO development while preserving established standards for content validity and psychometric rigor. Drawing on examples from development of the Eating Behavior Measurement (EBM) project and emerging literature from PRO science, survey methodology, and psychological measurement, we outline several bounded use cases for LLMs in PRO measure qualitative development workflows. These include accelerating synthesis of legacy item pools ("domain cartography"), generating candidate items within human-defined constructs, supporting iterative item revision in response to cognitive interview findings, conducting semantic coherence checks for construct alignment, and assisting with developmental or contextual adaptation of candidate items. Across these applications, LLMs function as structured drafting and analytic tools rather than arbiters of validity. We additionally discuss practical risks involving confirmation bias, semantic circularity, transparency, reproducibility, and construct drift, along with strategies for mitigation through human oversight and model triangulation. LLMs do not replace qualitative inquiry, expert judgment, or empirical psychometric validation. Rather, they may help support more systematic and scalable qualitative development workflows when used within bounded, human-centered measurement frameworks. The central challenge for PRO science is not whether to adopt these tools, but how to integrate them responsibly without compromising the evidentiary standards on which the field depends.
BA.3.2, a variant of SARS-CoV-2 containing ~40 mutations in its spike protein compared to its nearest ancestor, has spread globally since its first detection in South Africa in November 2024. Here, we report antigenic characterization of BA.3.2 viruses in three naive animal models, and visualize its antigenic phenotype in the context of SARS-CoV-2 evolution using antigenic cartography. We find that: (1) BA.3.2 is substantially antigenically divergent from existing SARS-CoV-2 variants; (2) infection with BA.3.2 in hamster and mouse animal models produces sera with lower homologous titer than infection with other variants. Both of these results may have implications for the selection of vaccine antigens.
The SARS-CoV-2 virus continues to evolve under immune selection pressure, leading to the emergence of antigenically distinct Omicron subvariants such as BA.3.2.2. This sublineage harbors extensive spike mutations, including numerous substitutions within the receptor-binding domain, suggesting potential immune escape from currently deployed vaccines. Given its increasing prevalence, we evaluated the neutralization capacity of variant-adapted vaccines against BA.3.2.2. Using Ad5/35-based adenoviral vaccines encoding JN.1 and LP.8.1 spike antigens, neutralizing antibody responses were assessed in murine and non-human primate models using a pseudotyped lentivirus assay. Antigenic cartography based on neutralization data demonstrated that BA.3.2.2 is antigenically distant from previously circulating variants. Although LP.8.1 vaccination broadened neutralization against multiple variants, neutralizing activity against BA.3.2.2 was markedly lower than that against LP.8.1 and other tested variants. Booster immunization further enhanced responses to matched variants but failed to restore neutralization against BA.3.2.2. These findings indicate that BA.3.2.2 exhibits substantial resistance to vaccine-induced neutralization, underscoring the urgent need for updated vaccine strategies to address newly emerging SARS-CoV-2 variants.
The SARS-CoV-2 BA.3.2.2 sublineage has emerged globally as the dominant branch of BA.3.2 by late 2025, yet its antigenic relationship with JN.1 vaccine-induced immunity remains unclear. We evaluated neutralizing antibody responses in 25 JN.1 mRNA vaccinees against eight variants, stratified by anti-nucleocapsid antibody serostatus. Post-vaccination titers increased significantly against all variants in both N antibody-negative and -positive groups. Cross-neutralization against BA.3.2.2 was detected in both groups despite lower titers compared to JN.1. Antigenic cartography revealed that BA.3.2.2 was antigenically isolated from all JN.1-descendant variants. AZD3152/sipavibart retained potent neutralization against BA.3.2.2 but completely lost activity against all F456L-harboring JN.1-descendant variants, while VYD222/pemivibart and SA55 maintained broad activity. Retention of wild-type F456 in BA.3.2.2 preserves class 1/2 antibody epitopes, providing a mechanistic basis for cross-neutralization and suggesting a potential therapeutic window for sipavibart should BA.3.2.2 expand globally, pending clinical confirmation.