Biology subjects

Yin, Q.

Publications and source records attributed to Yin, Q..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

High-temporal-resolution point-of-care multiplex biomarker monitoring in small animals using microfluidic digital ELISA

Time-course monitoring of blood biomarkers with rapid turnaround has the potential to revolutionize the diagnosis, stratification of phenotypes, and therapeutic/prognostic approaches for various acute inflammatory diseases in both clinical and preclinical studies. Current approaches, however, are hampered by slow turnaround times and large sample volume requirements, limiting the exploration of disease mechanisms and therapeutic strategies. Here, we developed a microfluidic digital ELISA platform prototype, combining single-molecule counting with whole blood assay capability for the first time from small animal models. This platform is automated and enables repeated, rapid biomarker monitoring with just 3.5 {micro}L of whole blood collected from the tail. Our platform demonstrated high sensitivity and multiplexity, allowing real-time cytokine profiling within a 2-hour turnaround. Using a murine sepsis model, we achieved precise temporal monitoring of cytokine levels, demonstrating prognostic capability by correlating early-stage cytokine levels with a liver-injury biomarker. This microfluidic platform enables high temporal resolution and rapid monitoring of biomarker dynamics in a single mouse using freshly collected whole blood, significantly reducing the number of animals needed for preclinical studies. This technology has strong potential to transform ICU therapeutic strategies and preclinical research, enabling personalized treatment based on real-time biomarker profiles.

bioengineering↗

bioRxiv2025

Explainable deep learning for identifying cancer driver genes based on the Cancer Dependency Map

Identifying cancer driver genes and their therapeutic impact remains a core challenge in computational cancer biology. We introduce xNNDriver and xAEDriver, two interpretable neural network frameworks that connect cancer mutations with genome-wide DepMap gene dependencies, pathway activity, and drug-response patterns. xNNDriver is a supervised pathway-guided model that evaluates whether a genes mutation status is encoded in the genome-wide dependency landscape; we interpret model fitness as a driver potential score, which quantifies the strength of this mutation-dependency signal and prioritizes genes with broad functional footprints. Across 3,008 candidate genes, xNNDriver recovers major established drivers and highlights literature-supported candidates, while pathway analyses reveal biologically coherent programs related to metabolism, growth factor signaling, and immune regulation. To capture combinatorial functional states, xAEDriver uses an unsupervised autoencoder to learn Driver Variant Representations (DVRs), latent binary features guided by the frequency distribution of known driver mutations. DVRs capture cell-line-specific dependency patterns and expression patterns and are associated with drug sensitivity and pathway activity. Together, these interpretable deep learning models demonstrate that gene dependency landscapes encode rich, interpretable signals of oncogenic function and provide a hypothesis-generating framework for prioritizing drivers, pathways, and therapeutic vulnerabilities for further experimental validation. Author summaryCancer is often driven by genetic changes that give tumor cells a growth advantage, but finding which changes matter and how they affect cell behavior remains difficult. In this study, we used large-scale gene-editing data from cancer cell lines to ask whether the pattern of genes a cell depends on can reveal information about its cancer-driving alterations. We developed interpretable neural-network models that connect mutation patterns, cell survival dependencies, and biological pathways. One model prioritizes genes whose mutation status leaves a clear functional signature across the cell. A second model summarizes broader, combined driver-like states in each cell line. These summaries were linked to known cancer biology, tissue type, and differences in drug response, suggesting that functional dependency data contain useful clues about cancer mechanisms. By connecting mutation patterns with functional dependencies and pathway activity, our approach helps identify candidate cancer drivers and interpretable drug-response patterns that can guide future experimental studies. Making the models interpretable allows researchers to move from large screening datasets toward biological explanations of cancer-driving processes.

bioinformatics↗

bioRxiv2025

Mice dynamically adapt to opponents in competitive multi-player games

Competing for resources in dynamic social environments is fundamental for survival and requires continuous monitoring of both self and others to guide effective choices. Yet most of our understanding of value-based decision-making comes from studying individuals in isolation, leaving open key questions about how animals adapt their strategies during social competition. Here, we developed an ethologically relevant multi-player game in which freely moving mice made valuebased decisions in a competitive spatial foraging task. We found that mice integrated real-time spatial information about both themselves and their opponents to flexibly shift their preferences toward safer, low-payout options when appropriate. Analyses of mice behaviour and reinforcement learning agents revealed that these adaptations could not be explained by simple reward learning, but were instead consistent with optimal decision strategies guided by opponent features. Using a dynamical model of decision-making, we found that competition increased choice variability and sensitivity to initial conditions, generating testable predictions for future neural recordings and perturbations. Together, our findings reveal a fundamental mechanism for flexible competitive foraging and propose novel frameworks for quantitatively understanding value-based decision-making in fast-changing social environments.

neuroscience↗

bioRxiv2025

Collective biosynthesis of plant spirooxindole alkaloids through enzyme discovery and engineering

Collective synthesis is a well-established strategy to produce natural product collections from common intermediates. Extending this concept to enzymatic systems, collective biosynthesis offers a sustainable approach to diverse molecular collections but faces distinct challenges, including incomplete pathway knowledge and narrow substrate specificity of biosynthetic enzymes. Here, we overcome these limitations through enzyme discovery and protein engineering to achieve collective biosynthesis of spirooxindole alkaloids, an important class of natural products with diverse biological activities. We identified two key enzymes that catalyze enzymatic epimerization, working sequentially with a previously discovered cytochrome P450 enzyme to fully elucidate the biosynthetic pathway of pentacyclic spirooxindole alkaloids. Structure-guided engineering expanded substrate scope, enabling collective biosynthesis of 12 tetracyclic and pentacyclic spirooxindole natural products. We also generated new-to-nature fluorinated and deuterated derivatives through precursor-directed biosynthesis. This work provides crucial insights into plant spirooxindole alkaloid biosynthesis while establishing a powerful approach for sustainable production of complex natural products.

biochemistry↗

bioRxiv2025

Declarative Memory Through the Lens of Single-Trial Peaks in High-Frequency Power

Declarative memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global network organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated throughout the network. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across the medial temporal lobe (MTL) and prefrontal cortex (PFC). HFB peak activity was earlier in the MTL than PFC. Anchoring analyses of theta phase clustering and connectivity to HFB peaks revealed strong phase clustering locked to HFB peaks in the PFC, as well as connectivity between the PFC and MTL that predicted individual memory performance. Graph analysis revealed specific connections amidst sparse network connectivity during memory success. This study demonstrates that transient brain states linked to internal physiological events support memory and refines our understanding of local and network-level process interactions. HighlightsO_LIMemory-linked theta activity is time-locked to internal brain events C_LIO_LINetwork connectivity changes dynamically during memory processing C_LIO_LISparse network connectivity supports successful memory C_LIO_LISpecific sequences of transient states may be critical for declarative memory C_LI

neuroscience↗

bioRxiv2024

The development of aperiodic neural activity in the human brain

The neurophysiological mechanisms supporting brain maturation are fundamental to attention and memory capacity across the lifespan. Human brain regions develop at different rates, with many regions developing into the third and fourth decades of life. Here, in this preregistered study (https://osf.io/gsru7), we analyzed intracranial EEG (iEEG) recordings from widespread brain regions in a large developmental cohort. Using task-based (i.e., attention to-be-remembered visual stimuli) and task-free (resting-state) data from 101 children and adults (5.93 - 54.00 years, 63 males; n electrodes = 5691), we mapped aperiodic (1/[f]-like) activity, a proxy of neural noise, with steeper slopes indexing less noise and flatter slopes indexing more noise. We reveal that aperiodic slopes flatten with age into young adulthood in both association and sensorimotor cortices, challenging models of early sensorimotor development based on brain structure. In prefrontal cortex (PFC), attentional state modulated age effects, revealing steeper task-based than task-free slopes in adults and the opposite in children, consistent with the development of cognitive control. Age-related differences in task-based slopes also explained age-related gains in memory performance, linking the development of PFC cognitive control to the development of memory. Last, with additional structural imaging measures, we reveal that age-related differences in gray matter volume are similarly associated with aperiodic slopes in association and sensorimotor cortices. Our findings establish developmental trajectories of aperiodic activity in localized brain regions and illuminate the development of PFC control during adolescence in the development of attention and memory.

neuroscience↗

bioRxiv2024

Structural basis of pseudoGTPase-mediated protein-protein interactions

GTPases regulate various cellular processes through conformational changes triggered by GTP or GDP binding. Recently, pseudoGTPases, the catalytically inactive counterparts of GTPases, have been identified across species from bacteria to human, although their functions and mechanisms remain unexplored. In this study, we demonstrate that the N-terminal region of the assembly chaperone AAGAB is a type i pseudoGTPase using biochemistry and X-ray crystallography. Furthermore, we discovered that the AAGAB pseudoGTPase domain (psGD) interacts with the {sigma} subunits of AP1 and AP2 adaptor complexes, heterotetrameric complexes involved in clathrin-mediated membrane trafficking. AAGAB psGD engages the {sigma} subunits via a unique interface distinct from the conventional GTPase interacting regions. Further biochemical and cell-based assays confirmed the crucial role of the newly identified interface in binding and membrane trafficking. Collectively, our results establish AAGAB pseudoGTPase domain as a critical protein-protein interaction module. These findings offer new insight into the structural basis and molecular mechanisms of pseudoGTPases. HighlightsO_LIAAGAB N-terminal region is a pseudoGTPase C_LIO_LIAAGAB pseudoGTPase domain interacts with and stabilizes AP1 and AP2 {sigma} subunits C_LIO_LIThe crystal structure of AAGAB psGD:AP1{sigma}3 is the first reported psGD complex structure, revealing a unique interface independent of guanine nucleotide regulation C_LIO_LIThe psGD:AP1{sigma}3 structure offers mechanistic insights into {sigma} subunits stabilization and protection through adaptor complex assembly C_LI

biochemistry↗

bioRxiv2024

CREATE: cell-type-specific cis-regulatory elements identification via discrete embedding

Identifying cis-regulatory elements (CREs) within non-coding genomic regions--such as enhancers, silencers, promoters, and insulators--is pivotal for elucidating the intricate gene regulatory mechanisms underlying complex biological traits. The current prevalent sequence-based methods often focus on singular CRE types, limiting insights into cell-type-specific biological implications. Here, we introduce CREATE, a multimodal deep learning model based on the Vector Quantized Variational AutoEncoder framework, designed to extract discrete CRE embeddings and classify multiple CRE classes using genomic sequences, chromatin accessibility, and chromatin interaction data. CREATE excels in accurate CRE identification and exhibits strong effectiveness and robustness. We showcase CREATEs capability in generating comprehensive CRE-specific feature spectrum, offering quantitative and interpretable insights into CRE specificity. By enabling large-scale prediction of CREs in specific cell types, CREATE facilitates the recognition of disease- or phenotype-related biological variabilities of CREs, thereby expanding our understanding of gene regulation landscapes.

bioinformatics↗

bioRxiv2024

Synergically enhanced anti-tumor immunity of in vivo CAR by circRNA vaccine boosting

Chimeric Antigen Receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies. However, it is limited to individualized cell therapy and faces challenges, including high costs, extended preparation time, and limited efficacy against solid tumors. Here, we generated circular RNAs (circRNAs) encoding Chimeric Antigen Receptor (CAR) transmembrane proteins, referred to as circRNACAR, which mediated remarkable tumor killing in both T cells and macrophages. In addition, macrophages exhibited efficient phagocytosis of tumor cells and pro-inflammatory polarization induced by circRNACAR in vitro. We demonstrated that circRNACAR, delivered with immunocyte-tropic lipid nanoparticles (LNPs), significantly inhibited tumor growth, improved survival rates and induced a pro-inflammatory tumor microenvironment in mice. Importantly, the combination of circRNAAnti-HER2-CAR and circRNA-based cancer vaccines encoding the corresponding transmembrane HER2 antigen, termed circRNAHER2, exhibited synergistically enhanced anti-tumor activity. This proof-of-concept study demonstrated that the combination of circRNA-based in vivo CAR and vaccines, termed in vivo CAR-VAC, holds the potential to become an upgraded off-the-shelf immunotherapy.

immunology↗

bioRxiv2024

Early mouse ovarian follicles develop into a thecal cell network that generates androgens during peri-puberty

The earliest growing mouse follicles, wave 1, rapidly develop in the ovarian medulla, while the great majority, wave 2, are stored for later use as resting primordial follicles in the cortex. Wave 1 follicles are known to mostly undergo atresia, a fate sometimes associated with the persistence of steroidogenic theca cells, but this connection is poorly understood. We characterized wave 1 follicle biology using tissue clearing, lineage tracing and scRNAseq to clarify their contributions to offspring and to steroidogenesis. Wave 1 follicles lineage marked by E16.5 FoxL2 expression in granulosa cells, reach preantral stages containing theca cell layers by 2 weeks. Atresia begins about a week later, during which 80-100% of wave 1 follicles degrade their oocytes, turn over most granulosa cells, but retain theca cells which expand in number together with interstitial gland cells in the medulla. During puberty (5 weeks), these cells ultrastructurally resemble steroidogenic cells and highly express androgen biosynthetic genes. Unexpectedly, the FoxL2 lineage tag also marked about 400 primordial follicles, located near the medullar-cortical boundary, that become the earliest-activated wave 2 follicles. These "boundary" or "wave 1.5" follicles generate 70-100% of the earliest mature oocytes, while fewer than 26 wave 1 follicles with oocytes survive. Consistent with their largely distinct fates in steroid or oocyte production, granulosa cells of antral wave 1 and wave 2 follicles differentially express multiple genes, including Wnt4 and Igfbp5. SIGNIFICANCE STATEMENTWe studied the ovaries of juvenile mice 2-6 weeks (wk) of age using transcriptomics and cell lineage to characterize the earliest developing groups of follicles. Wave 1 follicles begin growing at birth in the ovarian medulla, but few produce mature oocytes. Instead, most undergo partial atresia and expand steroidogenic cells expressing androgenic genes at puberty. A newly identified primordial follicle subset located at the medulla-cortex boundary are the earliest to activate and grow. Their oocytes give rise to most early offspring, while no more than a few derive from surviving wave 1 follicles. Our results highlight the importance of spatially localized follicle subgroups and show that follicular waves aid reproduction in distinct ways, some of which involve substantial atresia and cellular remodeling.

developmental biology↗

bioRxiv2024

Utilizing transcriptomics and metabolomics reveal drought tolerance mechanism in Nicotiana tabacum

The development and growth of plants are significantly impacted by adverse surroundings, particularly drought conditions. The yield and quality of plants, in particular, are heavily reliant on the presence of favorable growth conditions. Here, we performed comprehensive research to investigate phenotype, physiological characteristics, transcriptomic and metabolomic changes in Nicotiana tabacum (N. tabacum) in responses to drought stress (DS). This work aimed to investigate the detailed responses of N. tabacum to DS under different drought conditions (CK, well-watered; LD, light drought; MD, moderate drought and SD, severe drought). N. tabacum grew normally under CK but was inhibited under LD, MD and SD stress; the relative water content, transpiration rate and protective enzyme activity significantly influenced under DS. In the LD/CK, MD/CK and SD/CK comparison groups, there were 7483, 15558 and 16876 differentially expressed genes (DEGs), respectively, and 410, 485 and 523 differentially accumulated metabolites (DAMs), respectively. The combined analysis of transcriptomic and metabolomic data unveiled the significant involvement of phenylpropanoid biosynthesis in the N. tabacums response to drought stress. These findings characterized the key metabolites and genes in responses to drought stress in N. tabacum, hence offering valuable insights into the underlying mechanisms driving these responses to DS and maintaining plant health under climate change.

plant biology↗

bioRxiv2024

MePHD1.2 affects the synthesis of cyanogenic glycosides by regulating the transcription of MeCYP79D2 in cassava

The high content of cyanogenic glycosides (CG) in cassava storage tubers seriously affects human food safety. CG play crucial roles in plant growth and development and can protect cassava leaves from being masticated by herbivorous predators. Nevertheless, the regulatory mechanism of CG biosynthesis, which results in a low CG content in storage tubers and high CG content in leaves, remains poorly understood. Here, yeast one-hybrid assay was performed using a mixed cDNA library of cassava storage roots and leaves as prey and the promoter of MeCYP79D2 as bait. MeCYP79D2, a cytochrome P450 protein, is the rate-limiting enzyme for CG synthesis in cassava. From this information, a candidate regulator of MeCYP79D2, that is, transcription factor MePHD1.2, was selected. MePHD1.2, which is located in the nucleus and exhibits a transcription inhibitory activity, can directly bind to PD2 segment in the promoter of MeCYP79D2, which results in its repressed expression. In cassava, the transcriptional activity of MeCYP79D2 was considerably enhanced in mephd1.2 lines, which caused an increase in the contents of linamarin and lotaustralin. Our findings unveil a novel regulatory module governing CG biosynthesis, wherein mutation of MePHD1.2 attenuates its transcription inhibition on MeCYP79D2 and boosts CGs biosynthesis in cassava.

molecular biology↗

bioRxiv2024

A single cell atlas of the mouse seminal vesicle

During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations - including large populations of macrophages, dendritic cells, T cells, and NKT cells - which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.

genomics↗

bioRxiv2023

TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1alpha axis in melanoma

TIPE (TNFAIP8) has been identified as an oncogene and participates in tumor biology. However, how its role in the metabolism of tumor cells during melanoma development remains unclear. Here, we demonstrated that TIPE promoted glycolysis by interacting with pyruvate kinase M2 (PKM2) in melanoma. We found that TIPE induced PKM2 dimerization, thereby facilitating its translocation from the cytoplasm to the nucleus. TIPE-mediated PKM2 dimerization consequently promoted HIF-1 activation and glycolysis, which contributed to melanoma progression and increased its stemness features. Notably, TIPE specifically phosphorylated PKM2 at Ser 37 in an ERK-dependent manner. Consistently, the expression of TIPE was positively correlated with the levels of PKM2 Ser37 phosphorylation and cancer stem cell markers in melanoma tissues from clinical samples and tumor bearing mice. In summary, our findings indicate that the TIPE/PKM2/HIF-1 signaling pathway plays a pivotal role in promoting cancer stem cell properties by facilitating the glycolysis, which would provide a promising therapeutic target for melanoma intervention.

cancer biology↗

bioRxiv2023

Systems genetics identifies the association between Enc1 and cognitive function in the hippocampus

Ectodermal-Neural Cortex 1 (ENC1) is expressed in multiple regions of the brain, including the hippocampus. However, knowledge about its function has been well explored only in the context of peroxidative stress and cancer. In this study, we investigated the association of hippocampal Enc1 with cognitive function in BXD mice. We performed Pearson correlation, phenotype-wide association analysis (PheWAS), expression-Based PheWAS, pathway enrichment, and protein interaction networks on Enc1 and BXD phenotypes/transcriptome of the hippocampus, and the results indicated that Enc1 is inextricably linked to cognitive performance. In addition, we found that most of the Enc1 co-expressed genes were highly expressed in GABAergic neuronal cells. Expression quantitative trait loci analysis indicated that Enc1 was cis-regulated in the hippocampus of mice as well as human. Genome-wide association analysis revealed ENC1 to be significantly associated with cognitive-related traits, including age-related cognitive changes etc. In conclusion, our findings demonstrated that Enc1 is involved in cognitive functions mainly in hippocampal GABAergic neuronal cells through neurogenesis, synaptic signaling, and CGMP-PKG signaling pathways, and interacts with the neurological function-related genes.

genetics↗

bioRxiv2023

Crystal structures reveal nucleotide-induced conformational changes in G motifs and distal regions in guanylate-binding protein 2

Guanylate-binding proteins (GBPs) are interferon-inducible GTPases that confer protective immunity against a variety of intracellular pathogens including bacteria, viruses, and protozoan parasites. GBP2 is one of the two highly inducible GBPs, yet the precise mechanisms underlying the activation and regulation of GBP2, in particular the nucleotide-induced conformational changes in GBP2, remain poorly understood. In this study, we elucidate the structural dynamics of GBP2 upon nucleotide binding through crystallographic analysis. GBP2 dimerizes upon GTP hydrolysis and returns to monomer state once GTP is hydrolyzed to GDP. By determining the crystal structures of GBP2 G domain (GBP2GD) in complex with GDP and nucleotide-free full-length GBP2, we unveil distinct conformational states adopted by the nucleotide-binding pocket and distal regions of the protein. Our findings demonstrate that the binding of GDP induces a distinct closed conformation both in the G motifs and the distal regions in the G domain. The conformational changes in the G domain are further transmitted to the C-terminal helical domain, leading to large-scale conformational rearrangements. Through comparative analysis, we identify subtle but critical differences in the nucleotide-bound states of GBP2, providing insights into the molecular basis of its dimer-monomer transition and enzymatic activity. Overall, our study expands the understanding of the nucleotide-induced conformational changes in GBP2, shedding light on the structural dynamics governing its functional versatility. These findings pave the way for future investigations aimed at elucidating the precise molecular mechanisms underlying GBP2s role in the immune response and may facilitate the development of targeted therapeutic strategies against intracellular pathogens.

biochemistry↗

bioRxiv2023

A Quadrivalent mRNA immunization elicits potent immune responses against vaccinia and monkeypox viral antigens - a step closer to a broad orthopoxvirus vaccine

The global outbreak of the 2022 monkeypox virus infection of human raised the public health concerns of the threat of human-to-human transmission of zoonotic diseases. Given the evidence that other orthopoxviruses including cowpox and camelpox were also reported infectious to human, and that the reemerging risk of smallpox as a bioterrorist or accidental laboratory escape exists, there is an urgent need to develop a poxvirus vaccine with a broad protection of orthopoxviruses to stockpile for future emergency. Extensive studies of vaccinia virus (VACV) suggested that multiple VACV antigens, such as A27, L1, A33 and B5, showed high level similarity in terms of immunogenicity to their respective homologous antigens of other orthopoxviruses. These findings paved the ground for VACV antigens to be used as potential vaccine targets for development of a universal poxvirus vaccine. In this study, we construct a novel poxvirus vaccine candidate, mRNA-ALAB-LNP, encoding four vaccinia viral antigens A27, L1, A33 and B5. Strong anti-L1-specific antibody and moderate anti-A33-, anti-A27- and anti-B5-specific antibody responses were induced in mice after a single immunization. The antibody responses to all four antigens were significantly boosted after the second shot with all IgG titers >5 logs and highest being anti-A33 IgG. The high level of binding antibodies showed potent neutralizing capability against vaccinia virus. Specific IFN-{gamma} responses were detected to all four antigens with the highest cellular response being that induced by the same antigen, A33. When evaluating the cross reactivity, equivalent or better serum IgG responses were seen in responses to corresponding monkeypox antigens A35, M1, A29 and B6, in comparison to vaccinia antigens. Apparently, the mRNA vaccine encoding four vaccinia antigens induced immunity not only to vaccinia virus but also to monkeypox, suggesting that the mRNA-ALAB may be a candidate for potential vaccine development against infection of monkeypox, smallpox and possibly other orthopoxviruses.

immunology↗

bioRxiv2023

Engineered Immunogens to Expose Conserved Epitopes Targeted by Broad Coronavirus Antibodies

Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employed computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant RBD. These engineered proteins bound with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interacted with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicited sera with broad betacoronavirus reactivity and protected as "boosts" against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.

immunology↗