Biology subjects

van Rijswijk, J.

Publications and source records attributed to van Rijswijk, J..

5 recordsLinked to original sources

bioRxiv2026

Adjuvant selection for optimally balanced humoral and cellular immunity induced by SARS-CoV-2 Spike virosome vaccines

Current SARS-CoV-2 vaccines provide limited breadth of protection, underscoring the need for vaccine strategies that optimize immune responses. Virosomesoffer a modular vaccine platform that enables multivalent antigen display and incorporation of adjuvants which can steer immune responses. We evaluated the immune response in BALB/c mice with virosomes displaying SARS-CoV-2 Wuhan or Delta spike antigens and coupled with various distinct adjuvants. Adjuvant selection differentially influenced both humoral and cellular immune outcomes. The TLR7/8 agonist 3M -052 induced a strong Th1-biased response, characterized by elevated IgG2a/IgG1 ratios and robust type 1 cytokine induction with suppression of Th2-associated cytokines. In contrast, the saponin QS-21 enhanced antibody functional quality, illustrated by improved virus neutralization potency and breadth. Furthermore, the combined incorporation of both 3M-052 and QS-21 induced an elevated Th1-biased response without improving neutralization capacity. In conclusion, different adjuvants added onto our virosome-basedvaccine led to distinct antibody responses and splenic T-cell profiles, reflective of differences in immune programming. This information guides the selection of adjuvants for respiratory virus vaccines.

immunology↗

bioRxiv2026

Direct serological antibody discovery by integrative proteomics yields potent neutralizers overlooked by single-cell BCR sequencing

Human antibody discovery relies on accessing in vivo-matured repertoires, yet conventional single-cell B cell receptor sequencing (scBCR-seq) often overlooks the most relevant, functional antibodies secreted by plasma cells. Here, we introduce AbDirect, a protein-centric discovery platform that obtains antibody sequences directly from small-volume biofluids. In this proof-of-concept, we apply AbDirect to potent COVID-19 plasma from which an early-pandemic scBCR-seq study did not identify neutralizers. Upfront reactivity screening of anti-SARS-CoV-2 spike protein repertoires revealed diverse clonal profiles with distinct cross-reactivity and subunit specificity. Targeted de novo sequencing via standalone integrative proteomics yielded 14 IgG1 and 4 IgA1 clones that diverged markedly from peripheral B cell counterparts in germline usage and phylogeny, indicating distinct immunological compartments. Validation via recombinant mAbs demonstrated superior binding and highly potent neutralization for multiple sequenced clones (three with IC50 [≤]1.4 nM). AbDirect thus yielded potent antibodies overlooked by scBCR-seq, demonstrating serological discovery as a powerful complementary approach for uncovering functional repertoires that may be inaccessible to cell-based methods.

immunology↗

bioRxiv2025

Mapping brain volume changes in the zQ175DN mouse model of Huntington's disease: a longitudinal MRI study

Huntingtons disease (HD) is a progressive neurodegenerative disease affecting motor and cognitive abilities, as well as exhibiting psychiatric manifestations. Studies in people with HD (PwHD) consistently report atrophy of the caudate and putamen as an early pathological event and is therefore considered an early biomarker. Investigating whether similar phenotypic features are apparent in rodent HD models is important since it could have translational potential in evaluating the efficacy of novel therapeutic strategies. We used high-resolution anatomical images to longitudinally investigate brain morphology in the zQ175DN heterozygous mouse model (HET) and wildtype littermates (WT) at 3, 6, and 10 months of age (M), which reflect different stages of phenotypic progression. We investigated volumetric alterations using semi-automatic segmentations of HD on relevant regions-of-interest (striatum, cerebellum, corpus callosum, cerebral cortex, ventricles, and total brain volume) and whole brain voxel-wise Tensor Based Morphometry (TBM) analysis. The striatum showed the earliest progressive lower absolute volume in HET mice compared to WT, starting from 3M, followed by lower absolute volume of cortex and corpus callosum concomitantly at 6 and 10M. TBM highlighted lower relative local volume in the rostral-medial striatum at all ages, and in cerebral cortex in HET mice at 6 and 10M. A bigger relative local volume in the cerebellum was observed at all ages in HET mice, and in the globus pallidus, substantia nigra, at 6 and 10M. Overall, this study revealed key structural abnormalities that resemble the natural history of PwHD. Hence, analysis of brain structure through MRI in the zQ175DN heterozygous mouse model holds potential for testing disease-modifying treatments expected to slow down or prevent structural degeneration. HighlightsO_LIThe striatum of zQ175DN heterozygous mice shows volume decrease at 3 months compared to WT mice C_LIO_LIWidespread volume reductions are observed from 6 months in zQ175DN heterozygous mice C_LIO_LITensor Based Morphometry highlights vulnerability of the dorsomedial striatum in the zQ175DN heterozygous mouse model C_LI

neuroscience↗

bioRxiv2025

Multimodal single-cell analysis following SARS-CoV-2 breakthrough infection reveals distinct B cell populations

B cells underpin durable immunity by generating long-lived memory B cells and antibody-secreting cells (ASCs) that re-engage upon antigen re-encounter. How human IgG memory B cells are organized to establish, maintain, and reactivate humoral immunity remains incompletely understood. Here, we combine multimodal single-cell profiling with longitudinal characterization of antigen-specific memory B cells following SARS-CoV-2 infection and vaccination to define the developmental relationships and biological functions of human IgG memory B cell subsets. We identify a coordinated activation-memory cycle shared by germinal center- and extrafollicular-derived memory B cells marked by differential CD45RB expression. Within this cycle, activated B cells represent specialized effector cells that acquire inflammatory responsiveness, migratory capacity, and differentiation potential toward ASCs. Activated memory B cells persist as an intermediate that retains migratory capacity while shifting toward homeostatic survival, preserving recall competence and contributing to the regeneration of long-lived resting memory. The resting memory compartment comprises two complementary populations: CD73 resting memory B cells form the principal long-lived recall reservoir, whereas CD24 resting memory B cells adopt a more regulatory resting state and shows limited participation in the SARS-CoV-2 recall response. We further identify a CD24 intermediate population as the earliest transitional state emerging upon memory B cell reactivation, bridging resting memory and the effector recall response. Together, these findings establish the human IgG memory B cell compartment as a dynamic activation-memory cycle rather than a collection of static subsets, providing a framework for understanding humoral immunity and interpreting B cell responses in vaccination, infection, and immune-mediated disease. One sentence summaryOur results provide novel insights on B cell recall responses after SARS-CoV-2 infection or vaccination, formulating distinct classical and non-classical re-activation trajectories from a resting memory state through intermediate phenotypes towards an activated state.

immunology↗

bioRxiv2025

Longitudinal Investigation of Structural and Resting-State Effective Connectivity Alterations in a Non-Human Primate Model of Huntington's Disease

Huntingtons disease (HD) is a genetic neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene which produce a mutant huntingtin (mHTT) protein that contributes to progressive striatal, cortical, and white-matter atrophy, resulting in motor dysfunction and cognitive decline. Recently, a non-human primate (NHP) model of HD was developed via stereotaxic delivery of an adeno-associated viral vector expressing 85 CAG repeats (85Q) into the striatum. This model recapitulates several neuropathological changes and symptoms observed in people with HD (PwHD) including chorea and mild cognitive impairment. A previous longitudinal, multimodal MRI investigation in this model revealed volumetric and resting-state functional connectivity (rs-FC) changes compared to controls, in key regions involved in HD, over the course of 30 months. We aimed to study longitudinal changes in structural connectivity (SC), obtained from diffusion MRI scans from the same animals, comparing the 85Q animals to the control (Buffer) group. Additionally, going beyond the correlative rs-FC analyses, we investigated changes in causal, inter-regional functional interactions by estimating effective connectivity (EC) from rs functional MRI scans, constrained to strong structural connections. We found that the SC between basal ganglia regions and the cortex was reduced in the 85Q primates compared to the Buffer group at 14-months post virus injection, aligning with the pathological process observed in PwHD at later stages of the disease. EC from the caudate and putamen to the motor cortex was significantly reduced in the 85Q animals as early as 3-months post-injection providing novel insights into early alterations in causal functional interactions.

neuroscience↗