Biology subjects

Lin, Y.

Publications and source records attributed to Lin, Y..

At least 343 records · Page 19Linked to original sources

bioRxiv2021

Quantatitive Analysis of Conserved Sites on the SARS-CoV-2 Receptor-Binding Domain to Promote Development of Universal SARS-Like Coronavirus Vaccines

Although vaccines have been successfully developed and approved against SARS-CoV-2, it is still valuable to perform studies on conserved antigenic sites for preventing possible pandemic-risk of other SARS-like coronavirus in the future and prevalent SARS-CoV-2 variants. By antibodies obtained from convalescent COVID-19 individuals, receptor binding domain (RBD) were identified as immunodominant neutralizing domain that efficiently elicits neutralizing antibody response with on-going affinity mature. Moreover, we succeeded to define a quantitative antigenic map of neutralizing sites within SARS-CoV-2 RBD, and found that sites S2, S3 and S4 (new-found site) are conserved sites and determined as subimmunodominant sites, putatively due to their less accessibility than SARS-CoV-2 unique sites. P10-6G3, P07-4D10 and P05-6H7, respectively targeting S2, S3 and S4, are relatively rare antibodies that also potently neutralizes SARS-CoV, and the last mAbs performing neutralization without blocking S protein binding to receptor. Further, we have tried to design some RBDs to improve the immunogenicity of conserved sites. Our studies, focusing on conserved antigenic sites of SARS-CoV-2 and SARS-CoV, provide insights for promoting development of universal SARS-like coronavirus vaccines therefore enhancing our pandemic preparedness.

immunology↗

bioRxiv2021

Continuous Polony Gels for Tissue Mapping with High Resolution and RNA Capture Efficiency

Current technologies for acquiring spatial transcript information from tissue sections rely on either RNA probes or spatial barcodes. The former methods require a priori knowledge for probeset formulation; the latter have yet to achieve single cell resolution and/or transcript capture efficiencies approaching dissociative, single-cell methods. Here, we describe a novel spatial transcriptome assay called polony (or DNA cluster)-indexed library-sequencing (PIXEL-seq). It improves upon other spatial barcoding methods by employing "continuous" polony oligos arrayed across a customized gel surface. In terms of assay performance, PIXEL-seq attains [≤] 1 {micro}m resolution and captures >1,000 unique molecular identifiers/10x10 {micro}m2. In other words, this global, naive platform achieves subcellular spatial transcriptome mapping while maintaining high transcript capture efficiencies.

genomics↗

bioRxiv2021

Spatiospectral brain networks reflective of improvisational experience

Musical improvisers are trained to categorize certain musical structures into functional classes, which is thought to facilitate improvisation. Using a novel auditory oddball paradigm (Goldman et al., 2020) which enables us to disassociate a deviant (i.e. musical cord inversion) from a consistent functional class, we recorded scalp EEG from a group of musicians who spanned a range of improvisational and classically trained experience. Using a spatiospectral based inter and intra network connectivity analysis, we found that improvisers showed a variety of differences in connectivity within and between large-scale cortical networks compared to classically trained musicians, as a function of deviant type. Inter-network connectivity in the alpha band, for a time window leading up to the behavioural response, was strongly linked to improvisation experience, with the default mode network acting as a hub. Spatiospectral networks post response were substantially different between improvisers and classically trained musicians, with greater inter-network connectivity (specific to the alpha and beta bands) seen in improvisers whereas those with more classical training had largely reduced inter-network activity (mostly in the gamma band). More generally, we interpret our findings in the context of network-level correlates of expectation violation as a function of subject expertise, and we discuss how these may generalize to other and more ecologically valid scenarios.

neuroscience↗

bioRxiv2021

Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects

Cardiac arrhythmias are the most common cause of sudden cardiac death worldwide. Lengthening the ventricular action potential duration (APD) either congenitally or via pathologic or pharmacologic means, predisposes to a life-threatening ventricular arrhythmia, Torsade de Pointes. IKs, a slowly activating K+ current plays a role in action potential repolarization. In this study, we screened a chemical library in silico by docking compounds to the voltage sensing domain (VSD) of the IKs channel. Here we show that C28 specifically shifted IKs VSD activation in ventricle to more negative voltages and reversed drug-induced lengthening of APD. At the same dosage, C28 did not cause significant changes of the normal APD in either ventricle or atrium. This study provides evidence in support of a computational prediction of IKs VSD activation as a potential therapeutic approach for all forms of APD prolongation. This outcome could expand the therapeutic efficacy of a myriad of currently approved drugs that may trigger arrhythmias. Significance statementC28, identified by in silico screening, specifically facilitated voltage dependent activation of a cardiac potassium ion channel, IKs. C28 reversed drug-induced prolongation of action potentials, but minimally affected the normal action potential at the same dosage. This outcome supports a computational prediction of modulating IKs activation as a potential therapy for all forms of action potential prolongation, and could expand therapeutic efficacy of many currently approved drugs that may trigger arrhythmias.

biophysics↗

bioRxiv2021

Homologous and heterologous serological response to the N-terminal domain of SARS-CoV-2

The increasing numbers of infected cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious threats to public health and the global economy. Most SARS-CoV-2 neutralizing antibodies target the receptor binding domain (RBD) and some the N-terminal domain (NTD) of the spike protein, which is the major antigen of SARS-CoV-2. While the antibody response to RBD has been extensively characterized, the antigenicity and immunogenicity of the NTD protein are less well studied. Using 227 plasma samples from COVID-19 patients, we showed that SARS-CoV-2 NTD-specific antibodies could be induced during infection. As compared to the serological response to SARS-CoV-2 RBD, the SARS-CoV-2 NTD response is less cross-reactive with SARS-CoV. Furthermore, neutralizing antibodies are rarely elicited in a mice model when NTD is used as an immunogen. We subsequently demonstrate that NTD has an altered antigenicity when expressed alone. Overall, our results suggest that while NTD offers an alternative strategy for serology testing, it may not be suitable as an immunogen for vaccine development.

immunology↗

bioRxiv2021

Sexual Conflict Over Survival In Trinidadian Guppies

Differences in allele frequencies at autosomal genes between males and females in a population can result from two scenarios. Unresolved sexual conflict over survival produces allelic differentiation between the sexes. However, given the substantial mortality costs required to produce allelic differences between males and females at each generation, it remains unclear how many loci within the genome experience significant sexual conflict over survival. Alternatively, recent studies have shown that similarity between autosomal and Y sequence, arising from duplication onto the Y, can create perceived allelic differences, and this represents potentially resolved sexual conflict. However, Y duplications are most likely in species with large non-recombining regions, in part because they simply represent larger targets for duplications. We assessed the genomes of 120 wild-caught guppies, which experience extensive predation- and pathogen-induced mortality and have a relatively small ancestral Y chromosome. We identified seven autosomal genes that show allelic differences between male and female adults. Five of these genes show clear evidence of whole or partial gene duplication to the Y chromosome, suggesting that the male-specific region of the guppy Y chromosome, although relatively small, may nonetheless act as a hotspot for the resolution of sexual conflict. The remaining two genes show evidence of partial homology to the Y. Overall, our findings suggest that the guppy genome experiences a very low level of unresolved sexual conflict over survival, and instead the Y chromosome, despite its small ancestral size and recent origin, acts as a major mechanism of conflict resolution.

evolutionary biology↗

bioRxiv2021

High-throughput miRNA-sequencing of the human placenta: expression throughout gestation

BackgroundAltered placenta miRNA abundance may impact the maternal-fetal interface and pregnancy outcomes. Understanding miRNA changes across gestation is essential before miRNAs can be used as biomarkers or prognostic indicators during pregnancy. Materials & MethodsUsing next-generation sequencing, we characterize the normative human placenta miRNA transcriptome in first (N=113) and third trimester (N=47). ResultsThere are 801 miRNAs expressed in both first and third trimester, including 182 with similar expression across gestation (P[≥]0.05) and 182 significantly different (FDR<0.05). Of placenta-specific miRNA clusters, C14MC is more upregulated in first trimester and C19MC is more highly expressed overall. ConclusionThis work provides a rich atlas of healthy pregnancies to direct functional studies investigating the epigenetic differences in first and third trimester placentae. Lay AbstractThe human body produces microRNAs which affect the expression of genes and proteins. This study uses next generation sequencing to identify the microRNA profile of first and third trimester human placentae using a large cohort (N=113 first, N=47 third trimester). All pregnancies resulted in healthy babies. We identify microRNAs with significantly different expression between first and third trimester, as well as stably expressed microRNAs. This work provides a baseline for future studies which may use microRNAs to monitor maternal-fetal health throughout pregnancy.

developmental biology↗

bioRxiv2021

Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells.

Metastases are initiated by disseminated tumor cells (DTCs) that depart from the primary tumor and colonize target organs. Growing evidence suggests that the microenvironment of the primary tumor lesion primes DTCs to display dormant or proliferative fates in target organs. However, the manner in which events taking place in the primary tumor influence DTC fate, sometimes long after dissemination, remains poorly understood. With the advent of a novel intravital imaging technique called the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we have, for the first time, been able to study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find, across several models, a high rate of success for tumor cells to complete the initial steps of the metastatic cascade in the secondary site, including retention of DTCs in the lung vasculature, speed of extravasation, and survival after extravasation. Importantly, initiation of metastatic growth was controlled primarily by a rate-limiting step that occurred post-extravasation and at the stage of the conversion of single DTCs from a dormant to a proliferative state. Detailed analysis of these events revealed that, even before dissemination, a subset of macrophages within the primary tumor induces, in tumor cells that are about to disseminate, the expression of proteins that regulate a pro- dissemination (MenaINV) and pro-dormancy (NR2F1) phenotype. Surprisingly, if cancer cells are intravenously injected, the rate limiting stages of MenaINV-associated extravasation, dormancy, and other parameters, are lost or altered in a way that impacts how DTCs progress through the metastatic cascade. Our work provides novel insight into how specific primary tumor microenvironments prime a subpopulation of cells for dissemination and dormancy. We also propose that dissecting mechanisms of metastasis, or testing anti-metastatic therapies, may yield results of limited application if derived from models that do not follow spontaneous dissemination. SIGNIFICANCEThis study provides important insight into the contribution of primary tumor microenvironmental niches to cancer metastasis by identifying the manner in which these niches spawn subpopulations of DTCs that are primed for dissemination and dormancy in the secondary site. This study may provide novel targets that could be inhibited to prevent successful colonization of the secondary site and, hence, metastasis.

cancer biology↗

bioRxiv2021

Lipid fingerprints are similar between SLC6 transporters in the neuronal membrane

We use molecular dynamics simulations to characterise the local lipid annulus, or "fingerprint", of three SLC6 transporters (dDAT, hSERT, and GlyT2) embedded into a complex neuronal membrane. New membrane analysis tools were created to improve leaflet detection and leaflet-dependent properties. Overall, lipid fingerprints are comprised of similar lipids when grouped by headgroup or tail saturation. The enrichment and depletion of specific lipids, including sites of cholesterol contacts, varies between transporters. The subtle differences in lipid fingerprints results in varying membrane biophysical properties near the transporter. Through comparisons to previous literature, we highlight that the lipid-fingerprint in complex membranes is highly dependent on membrane composition. Furthermore, through embedding these transporters in a simplified model membrane, we show that the simplified membrane is not able to capture the biophysical properties of the complex membrane. Our results further characterise how the presence and identity of membrane proteins affects the complex interplay of lipid-protein interactions, including the local lipid environment and membrane biophysical properties. HIGHLIGHTSO_LILipid fingerprints are comprised of similar lipid classes C_LIO_LISites of specific lipid contacts, including CHOL, varies between transporters C_LIO_LIChanges in lipid annulus result in variable local membrane biophysical properties C_LIO_LIMembrane composition, including that of complex membranes, affects lipid annulus C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/427530v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@ae6ee9org.highwire.dtl.DTLVardef@1f39af0org.highwire.dtl.DTLVardef@412256org.highwire.dtl.DTLVardef@355f1c_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2021

Cepo uncovers cell identity through differential stability

We present Cepo, a method to generate cell-type-specific gene statistics of differentially stable genes from single-cell RNA-sequencing (scRNA-seq) data to define cell identity. Cepo outperforms current methods in assigning cell identity and enhances several cell identification applications such as cell-type characterisation, spatial mapping of single cells, and lineage inference of single cells.

systems biology↗

bioRxiv2021

Decoding the single-cell landscape and intercellular crosstalk in the transplanted liver: a 4-dimension mouse model

Graft remodeling after transplantation maintains graft functionality and determines graft survival. However, a comprehensive understanding of cellular diversity and interplay during graft remodeling remains to be fully characterized. In this study, we established a well tolerant C57BL/6 to C57BL/6 orthotopic liver transplantation (LT) mice model and observed two stages of graft recovery including an acute phase and a steady phase. We next performed single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) and recorded the cellular hierarchy in the transplanted liver during the two stages. Besides the dynamic change of cell proportion, it was notable that recipient-derived cells took over the transplanted liver in most cell types (e.g., B cells, T cells, dendritic cells, granulocytes and monocytes) except CD206+ MerTK+ macrophages and CD161+ CD49a+ CD49b-natural killer cells. We then focused on macrophages and captured 5 distinct transcriptional signatures to define novel subclusters. Using a ligand-receptor interaction strategy, we identified specific macrophage-hepatocyte interactions during the acute and stable phases, causing metabolic remodeling in the transplanted liver. Our results delineated a 4-dimension cell atlas (type-proportion-source-time) of the transplanted liver, which sheds light on the physiological process of liver graft maintenance and graft-recipient crosstalk.

immunology↗

bioRxiv2021

Chromosome-scale assembly of the Sparassis latifolia genome obtained using long-read and Hi-C sequencing

Sparassis latifolia is a valuable edible mushroom cultivated in China. In 2018, our research group reported an incomplete and low quality genome of S. latifolia was obtained by Illumina HiSeq 2500 sequencing. These limitations in the available genome have constrained genetic and genomic studies in this mushroom resource. Herein, an updated draft genome sequence of S. latifolia was generated by Oxford Nanopore sequencing and the Hi-C technique. A total of 8.24 Gb of Oxford Nanopore long reads representing ~198.08X coverage of the S. latifolia genome were generated. Subsequently, a high-quality genome of 41.41 Mb, with scaffold and contig N50 sizes of 3.31 Mb and 1.51 Mb, respectively, was assembled. Hi-C scaffolding of the genome resulted in 12 pseudochromosomes containing 93.56% of the bases in the assembled genome. Genome annotation further revealed that 17.47% of the genome was composed of repetitive sequences. In addition, 13,103 protein-coding genes were predicted, among which 98.72% were functionally annotated. BUSCO assay results further revealed that there were 92.07% complete BUSCOs. The improved chromosome-scale assembly and genome features described here will aid further molecular elucidation of various traits, breeding of S. latifolia, and evolutionary studies with related taxa. ImportanceSparassis latifolia Y.C. Dai et Z. Wang (Sparassidaceae, Polyporales, Agaricomycetes), collections from Asian Sparassis (Dai et al., 2006) exhibits diverse biological and pharmacologic activities. To date, total fresh fruit production in Chinese factories is over 20 tons/d. Despite the significant economic and medical value of S. latifolia, the assembly level of genome was under chromosome-scale. This study assembles a high-quality chromosome-scale reference genome of S. latifolia using Oxford Nanopore sequencing combined with Hi-C (High-through chromosome conformation capture) scaffolding. The improved reference genome will facilitate molecular breeding of S. latifolia and advance our understanding of its genetics and evolution.

genomics↗

bioRxiv2021

scJoint: transfer learning for data integration of single-cell RNA-seq and ATAC-seq

Single-cell multi-omics data continues to grow at an unprecedented pace, and effectively integrating different modalities holds the promise for better characterization of cell identities. Although a number of methods have demonstrated promising results in integrating multiple modalities from the same tissue, the complexity and scale of data compositions typically present in cell atlases still pose a significant challenge for existing methods. Here we present scJoint, a transfer learning method to integrate atlas-scale, heterogeneous collections of scRNA-seq and scATAC-seq data. scJoint leverages information from annotated scRNA-seq data in a semi-supervised framework and uses a neural network to simultaneously train labeled and unlabeled data, enabling label transfer and joint visualization in an integrative framework. Using multiple atlas data and a biologically varying multi-modal data, we demonstrate scJoint is computationally efficient and consistently achieves significantly higher cell type label accuracy than existing methods while providing meaningful joint visualizations. This suggests scJoint is effective in overcoming the heterogeneity in different modalities towards a more comprehensive understanding of cellular phenotypes.

bioinformatics↗

bioRxiv2021

Single-cell and single-variant resolution analysis of clonal evolution in human liver cancer

Genetic heterogeneity of tumor is closely related to clonal evolution, phenotypic diversity and treatment resistance. Such heterogeneity has been characterized in liver cancer at single-cell sub-chromosomal scale, and a more precise single-variant resolution analysis is lacking. Here we employed a strategy to analyze both the single-cell genomic mutations and transcriptomic changes in 5 patients with liver cancer. Target sequencing was done for a total of 480 single cells in a patient-specific manner. DNA copy number status of point mutations was obtained from single-cell mutational profiling. The clonal structures of liver cancers were then uncovered at single-variant resolution, and mutation combinations in single cells enabled reconstruction of their evolutionary history. A common origin but independent evolutionary fate was revealed for primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. The mutational signature suggested early evolutionary process may be related to specific etiology like aristolochic acids. By parallel single-cell RNA-Seq, the transcriptomic phenotype was found to be related with genetic heterogeneity in liver cancer. We reconstructed the single-cell and single-variant resolution clonal evolutionary history of liver cancer, and dissection of both genetic and phenotypic heterogeneity provides knowledge for mechanistic understanding of liver cancer initiation and progression.

genomics↗

bioRxiv2020

Characterization of cell-cell communication in COVID-19 patients

COVID-19 patients display a wide range of disease severity, ranging from asymptomatic to critical symptoms with high mortality risk. Our ability to understand the interaction of SARS-CoV-2 infected cells within the lung, and of protective or dysfunctional immune responses to the virus, is critical to effectively treat these patients. Currently, our understanding of cell-cell interactions across different disease states, and how such interactions may drive pathogenic outcomes, is incomplete. Here, we developed a generalizable workflow for identifying cells that are differentially interacting across COVID-19 patients with distinct disease outcomes and use it to examine five public single-cell RNA-seq datasets with a total of 85 individual samples. By characterizing the cell-cell interaction patterns across epithelial and immune cells in lung tissues for patients with varying disease severity, we illustrate diverse communication patterns across individuals, and discover heterogeneous communication patterns among moderate and severe patients. We further illustrate patterns derived from cell-cell interactions are potential signatures for discriminating between moderate and severe patients.

systems biology↗

bioRxiv2020

A general approach to explore prokaryotic protein glycosylation reveals the unique surface layer modulation of an anammox bacterium.

The enormous chemical diversity and strain variability of prokaryotic protein glycosylation makes a large-scale exploration exceptionally challenging. Therefore, despite the universal relevance of protein glycosylation across all domains of life, the understanding of their biological significance and the evolutionary forces shaping oligosaccharide structures remains highly limited. Here, we report on a newly established mass binning glycoproteomics approach that establishes the chemical identity of the carbohydrate components and performs untargeted exploration of prokaryotic oligosaccharides from large-scale proteomics data directly. We demonstrate our approach by exploring an enrichment culture of the globally relevant anaerobic ammonium-oxidizing bacterium Ca. Kuenenia stuttgartiensis. By doing so we resolved a remarkable array of oligosaccharides, produced by two entirely unrelated glycosylation machineries targeting the same surface-layer protein (SLP) simultaneously. More intriguingly, the investigated strain also accomplished modulation of highly specialized sugars, supposedly in response to its energy metabolism--the anaerobic oxidation of ammonium --which depends on the acquisition of substrates of opposite charge. Ultimately, we provide a systematic approach for the compositional exploration of prokaryotic protein glycosylation, and reveal for the first time a remarkable balance between maximising cellular protection through a complex array of oligosaccharides and adhering to the requirements of the metabolic lifestyle.

systems biology↗

bioRxiv2020

Adaptation of Bacillus thuringiensis to plant colonisation affects differentiation and toxicity

Bacillus cereus group (Bacillus cereus sensu lato) has a diverse ecology, including various species that are vertebrate or invertebrate pathogens. Few isolates from the B. cereus group have however been demonstrated to benefit plant growth. Therefore, it is crucial to explore how bacterial development and toxicity evolves during plant colonization. Herein, we investigated Bacillus thuringiensis (Cry-) adaptation to the colonization of Arabidopsis thaliana roots, and monitored changes in cellular differentiation in experimentally evolved isolates. Isolates from two populations displayed improved iterative ecesis on roots and increased toxicity against insect larvae. Molecular dissection and recreation of a causative mutation revealed the importance of a non-sense mutation in the rho transcription terminator gene. Transcriptome analysis revealed how Rho impacts various B. thuringiensis genes involved in carbohydrate metabolism and virulence. Our work suggests that evolved multicellular aggregates have a fitness advantage over single cells when colonizing plants, creating a trade-off between swimming and multicellularity in evolved lineages, in addition to unrelated alterations in pathogenicity. ImportanceBiologicals-based plant protection relies on the use of safe microbial strains. During application of biologicals to the rhizosphere, microbes adapt to the niche, including genetic mutations shaping the physiology of the cells. Here, the experimental evolution of Bacillus thuringiensis lacking the insecticide crystal toxins was examined on the plant root to reveal how adaptation shapes the differentiation of this bacterium. Interestingly, evolution of certain linages led to increased emetic toxin production, hemolysis and insect larvae pathogenesis in B. thuringiensis driven by transcriptional rewiring. Further, our detailed study reveals how inactivation of the transcription termination protein Rho promotes aggregation on the plant root in addition to altered differentiation and pathogenesis in B. thuringiensis.

microbiology↗

bioRxiv2020

A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model

A novel multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and disease is described in this report. The initial development and characterization experiments are presented along with proof-of-concept studies for the vaccine candidate UB-612. UB-612 consists of eight components rationally designed for induction of potently neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist at low concentration as an excipient, and aluminum phosphate adjuvant. Through immunogenicity studies in Guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provides excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses. In challenge studies, UB- 612 vaccination reduced viral load and prevented development of disease in mouse and non-human primate challenge models. With a Phase 1 trial completed, a Phase 2 trial ongoing in Taiwan, and additional trials planned to support global authorizations, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 infection and COVID-19 disease. Author SummarySARS-CoV-2 virus, the causative agent of Coronavirus Disease 2019 (COVID-19), has spread globally since its origin in 2019, causing an unprecedented public health crisis that has resulted in greater than 4.7 million deaths worldwide. Many vaccines are under development to limit disease spread and reduce the number of cases, but additional candidates that promote a robust immune response are needed. Here, we describe a multitope protein-peptide vaccine platform that is unique among COVID-19 vaccines. The advantages of our approach are induction of both high levels of neutralizing antibodies as well as a Th/CTL response in the vaccinated host, which mimics the immune response that occurs after natural infection with SARS-CoV-2. We demonstrate that our vaccine is immunogenic and effective in preventing disease in several animal models, including AAV- hACE-2 transduced mice, and both rhesus and cynomolgus macaques. Importantly, no immunopathology was observed in the lungs of immunized animals, therefore showing that antibody-dependent enhancement (ADE) does not occur. Our study provides an additional, novel vaccine candidate for advancement in clinical trials to treat and prevent SARS-CoV-2 infection and COVID-19 disease.

immunology↗