Biology subjects

Wu, N.

Publications and source records attributed to Wu, N..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Computational studies reveal structural characterization and novel families of Puccinia striiformis f. sp. tritici effectors

Understanding the biological functions of Puccinia striiformis f. sp. tritici (Pst) effectors is fundamental for uncovering the mechanisms of pathogenicity and variability, thereby paving the way for developing durable and effective control strategies for stripe rust. However, due to the lack of an efficient genetic transformation system in Pst, progress in effector function studies has been slow. Here, we modeled the structures of 15,201 effectors from twelve Pst races or isolates, a Puccinia striiformis isolate, and one Puccinia striiformis f. sp. hordei isolate using AlphaFold2. Of these, 8,102 folds were successfully predicted, and we performed sequence- and structure-based annotations of these effectors. These effectors were classified into 410 structure clusters and 1,005 sequence clusters. Sequence lengths varied widely, with a concentration between 101-250 amino acids, and motif analysis revealed the presence of known effector motifs such as [Y/F/W]xC and RxLR. Subcellular localization predictions indicated a predominant cytoplasmic localization, with notable chloroplast and nuclear presence. Clear annotations based on sequence and structure included superoxide dismutase and trehalose-6-phosphate phosphatase. A common feature observed was the formation of similar structures from different sequences. In our study, one of the comparative structural analyses revealed a new structure family with a core structure of four helices, including Pst27791, PstGSRE4, and PstSIE1, which target key wheat immune pathway proteins, impacting the host immune function. Further comparative structural analysis showed similarities between Pst effectors and effectors from other pathogens such as AvrSr35, AvrSr50, Zt-KP4-1, and MoHrip2, highlighting convergent evolutionary strategies. This comprehensive analysis provides novel insights into Pst effectors structural and functional characterization, advancing our understanding of Pst pathogenicity and evolution. Author SummaryStripe rust, caused by the fungus Puccinia striiformis f. sp. tritici (Pst), is a major threat to wheat crops worldwide. The fungus uses special proteins, called effectors, to bypass the plants immune defenses and establish infection. To better understand how these effectors work, we used a computational tool, AlphaFold2, to predict the structures of over 15,000 Pst effector proteins. Interestingly, some of the effectors resemble proteins found in other plant pathogens, suggesting that different fungi may evolve similar ways to infect plants. Our research offers new insights into the infection strategies of Pst and could lead to new methods for protecting wheat from stripe rust.

microbiology↗

bioRxiv2024

Broken time reversal symmetry in visual motion detection

Our intuition suggests that when a movie is played in reverse, our perception of motion in the reversed movie will be perfectly inverted compared to the original. This intuition is also reflected in many classical theoretical and practical models of motion detection. However, here we demonstrate that this symmetry of motion perception upon time reversal is often broken in real visual systems. In this work, we designed a set of visual stimuli to investigate how stimulus symmetries affect time reversal symmetry breaking in the fruit fly Drosophilas well-studied optomotor rotation behavior. We discovered a suite of new stimuli with a wide variety of different properties that can lead to broken time reversal symmetries in fly behavioral responses. We then trained neural network models to predict the velocity of scenes with both natural and artificial contrast distributions. Training with naturalistic contrast distributions yielded models that break time reversal symmetry, even when the training data was time reversal symmetric. We show analytically and numerically that the breaking of time reversal symmetry in the model responses can arise from contrast asymmetry in the training data, but can also arise from other features of the contrast distribution. Furthermore, shallower neural network models can exhibit stronger symmetry breaking than deeper ones, suggesting that less flexible neural networks promote some forms of time reversal symmetry breaking. Overall, these results reveal a surprising feature of biological motion detectors and suggest that it could arise from constrained optimization in natural environments. SignificanceIn neuroscience, symmetries can tell us about the computations being performed by a circuit. In vision, for instance, one might expect that when a movie is played backward, ones motion percepts should all be reversed. Exact perceptual reversal would indicate a time reversal symmetry, but surprisingly, real visual systems break this symmetry. In this research, we designed visual stimuli to probe different symmetries in motion detection and identify features that lead to symmetry breaking in motion percepts. We discovered that symmetry breaking in motion detection depends strongly on both the detectors architecture and how it is optimized. Interestingly, we find analytically and in simulations that time reversal symmetries are broken in systems optimized to perform with natural inputs.

neuroscience↗

bioRxiv2024

rarestR: An R package using rarefaction metrics to estimate α-diversity (species richness) and β-diversity (species shared) for incomplete samples

Species abundance data is commonly used to study biodiversity patterns. In this context, estimating - and {beta}-diversity based on incomplete samples can lead to undersampling biases. It is therefore essential to employ methods that enable accurate comparisons of - and {beta}-diversity across varying sample sizes. This involves relying on biodiversity measures that are focused on accurately estimating the total number of species within a community, as well as the total number of species shared by two communities. Rarefaction offers such a method, where -diversity is estimated for standardized sample sizes. Rarefaction methods can also be used as a basis for {beta}-diversity calculations for standardized sample sizes. In this application note, we introduce a new R package, rarestR, designed to estimate abundance-based - and {beta}-diversity measures for inconsistent samples using rarefaction metrics. Additionally, the package offers parametric extrapolations to estimate the total expected number of species within a single community and the total expected number of species shared between two communities. Furthermore, it provides visualization for the curve fitting associated with these estimators. Overall, the rarestR package is useful in estimating - and {beta}-diversity values for incomplete samples, for example in studies involving highly mobile or species-rich taxa. These species estimators offer a complementary approach to non-parametric methods, such as the Chao series of estimators.

ecology↗

bioRxiv2024

Impaired central pattern generators due to abnormal EPHA4 signaling leads to idiopathic scoliosis

Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we firstly reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate genes across several large IS cohorts encompassing Chinese, East Asian, and European populations. Consequently, we identified variants in the EPHA4 gene as compelling candidates for IS. To confirm their pathogenicity, we generated zebrafish mutants of epha4a. Remarkably, the zebrafish epha4a mutants exhibited pronounced scoliosis during later stages of development, effectively recapitulating the IS phenotype. We observed that the epha4a mutants displayed defects in left-right coordination during locomotion, which arose from disorganized neural activation in these mutants. Our subsequent experiments indicated that the disruption of the central pattern generator (CPG) network, characterized by abnormal axon guidance of spinal cord interneurons, contributed to the disorganization observed in the mutants. Moreover, when knocked down efnb3b, the ligand for Epha4a, we observed similar CPG defects and disrupted left-right locomotion. These findings strongly suggested that ephrin B3-Epha4 signaling is vital for the proper functioning of CPGs, and defects in this pathway could lead to scoliosis in zebrafish. Furthermore, we identified two cases of IS in NGEF, a downstream molecule in the EPHA4 pathway. Collectively, our data provide compelling evidence that neural patterning impairments and disruptions in CPGs may underlie the pathogenesis of IS.

genetics↗

bioRxiv2024

Differences in milk microbiota between healthy cows and cows with recurring Klebsiella mastitis

Klebsiella spp. infections continue to have a significant economic impact on the dairy industry, being an important cause of severe clinical mastitis, recurrent infections, and demonstrating poor response to antimicrobials. It is, therefore, essential to investigate the underlying causes of Klebsiella spp. infections. Here we used high-throughput DNA sequencing to characterize the milk microbiota of healthy dairy cows (HDC) and cows with history of recurrent Klebsiella mastitis (KLB). Our goal was to identify potential pathogenic genera associated with recurrent Klebsiella infections in cows. The relative abundance of Firmicutes and Faecalibacterium was greater in the KLB group than in the HDC group. In contrast, Proteobacteria and Labrenzia were less abundant than in the HDC group. Although the species distributions differed between groups, diversity and abundance of communities were comparable. Notably, genera of increased occurrence in the KLB group were mostly intestinal-associated, which suggests that cows in the KLB group resided in a contaminated environment or had increased teat-end exposure to fecal bacteria. We did not detect major differences in microbiota among quarters, and also between fore-strip milk and milk collected after fore-stripping. Conversely, milk of heifers had increased alpha diversity in comparison to milk of multiparous cows.

microbiology↗

bioRxiv2024

Metabolomics unveiled the impact of alterations in nucleotide glucose metabolism on palmitic acid-induced TLR4 activation in THP-1 macrophages

OBJECTIVEThe association of palmitic acid with macrophage inflammation and its promotion of the expression of inflammatory factors through TLR4 have been demonstrated. It has been observed that immature TLR4 localizes to the endoplasmic reticulum and Golgi apparatus, necessitating glycosylation for migration to the cell membrane. The objective of this study was to identify potential biomarkers associated with N-glycosylation subsequent to the activation of TLR4 inflammatory signaling in human macrophages by palmitic acid. APPROACH AND RESULTSThe co-cultivation of palmitic acid with THP-1 macrophages was conducted for a duration of 24 hours, followed by the collection of cell extracts for subsequent metabolomic and lipidomic analyses using high performance liquid chromatography-tandem mass spectrometry. Multivariate and univariate statistical analyses were conducted to identify potential biomarkers, in accordance with established scientific protocols. The impact of palmitic acid on the TLR4 signaling pathway and macrophage N-glycosylation was assessed at various time points using Western blot analysis, immunofluorescence staining, Elisa assays, and chemical labeling techniques. The TLR4 inflammatory signaling pathway was examined in macrophages at different time points, revealing that PA induced the upregulation of MyD88 and TRAF6 expression as well as NF-{kappa}B phosphorylation, indicating the activation of classical NF-{kappa}B signaling. After 24 hours, TLR4 translocated from the cell membrane to the cytoplasm and initiated internalization, accompanied by significant colocalization with GalAz in the cytosol. In addition, the metabolites in the cell extract were found to be altered in both the control and model groups. Significantly alterations in two N-glycosylation related metabolites were observed in the model group, including guanosine diphosphate-L-fucose and uridine diphosphate-N-acetylglucosamine/uridine diphosphate-N-acetylgalactosamine. CONCLUSIONSTHP-1 macrophages incubated with palmitic acid exhibited a distinct metabolomic profile compared to the control group. Our findings suggest that metabolomics analysis holds promise in identifying disease-specific biomarkers for diagnosing fatty acid-induced inflammatory responses in macrophages.

immunology↗

bioRxiv2023

Gut microbiota promotes pain in fibromyalgia

Fibromyalgia is a chronic syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. Despite affecting 2-4% of the population, primarily women1, the cause and underlying mechanisms of fibromyalgia remain elusive, and effective targeted treatments are currently unavailable. The gut microbiota of women with fibromyalgia differs from healthy controls2,3. However, it is unknown whether changes in gut microbiota have a causal role in mediating pain and other symptoms of fibromyalgia. Here, we show that fecal microbiota transplantation (FMT) from individuals with fibromyalgia, but not from healthy controls, into germ-free mice induces persistent pain hypersensitivity. FMT from fibromyalgia patients led to a reduction in intraepidermal nerve fiber density and alterations in the peripheral immune profile, and induced activation of spinal microglia, which contributed to the development of pain in mice. Notably, the pain hypersensitivity in mice that were administered microbiota from fibromyalgia patients resolved after FMT from healthy controls. Consistent with these findings, an open-label pilot study showed that transplanting microbiota from healthy individuals to humans with fibromyalgia alleviated pain and reduced overall symptom severity. Thus, altered gut microbiota has a causal role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.

neuroscience↗

bioRxiv2023

ASD mutation of Katnal2 impairs ependymal ciliary motion and causes hydrocephalus

Katanin catalytic subunit A1 like 2 (KATNAL2) is a high-risk gene associated with autism spectrum disorders (ASD), however its impact on brain development and disease remains unclear. The present study revealed an unexpected role of KATNAL2 in regulating ependymal ciliary motion and cerebrospinal fluid flow during brain development, an important contributing factor for ASD. We discovered a distinct expression pattern of KATNAL2 in multiciliated ependymal cells of both human and mouse brains. Notably, an ASD-associated mutation of Katnal2 disrupted its molecular function and resulted in ASD-related behavioral deficits in mice. Additionally, this mutation affected the polarized organization and beating of ependymal cilia, leading to delayed cerebrospinal fluid flow and sustained ventricular enlargement from the early postnatal stage. Conditional ablation of Katnal2 specifically in the ependymal cells of neonatal mice is sufficient to cause ventricular dilation, whereas no such effect was observed in adult mice. Our findings highlight the importance of ependymal motile cilia and hydrocephalus in ASD, offering insights into its pathogenesis and potential intervention.

neuroscience↗

bioRxiv2023

Individualized network analysis reveals a link between the gut microbiome, diet intervention and Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM), a serious complication during pregnancy which is defined by abnormal glucose regulation, is commonly treated by diabetic diet and lifestyle changes. While recent findings place the microbiome as a natural mediator between diet interventions and diverse disease states, its role in GDM is still unknown. Here, based on observation data from healthy pregnant control group and GDM patients, we developed a new network approach using patterns of co-abundance of microorganism to construct microbial networks that represent human-specific information about gut microbiota in different groups. By calculating network similarity in different groups, we analyze the gut microbiome from 27 GDM subjects collected before and after two weeks of diet therapy compared with 30 control subjects to identify the health condition of microbial community balance in GDM subjects. Although the microbial communities remain similar after the diet phase, we find that the structure of their inter-species co-abundance network is significantly altered, which is reflected in that the ecological balance of GDM patients was not "healthier" after the diet intervention. In addition, we devised a method for individualized network analysis of the microbiome, thereby a pattern is found that individuals with large deviations in microbial networks are usually accompanied by their abnormal glucose regulation. This approach may help the development of individualized diagnosis strategies and microbiome-based therapies in the future. Author SummaryIn this study, we aimed to investigate the role of the gut microbiome in gestational diabetes mellitus (GDM), a condition that affects pregnant women and is characterized by abnormal glucose regulation. Specifically, we asked whether and how the gut microbiome is affected by diabetic diet which is commonly used to treat GDM patients. We developed a new network approach to analyze patterns of co-abundance of microorganisms in the gut microbiota of GDM patients and healthy pregnant women. Our findings show that although the microbial communities remained similar after the diet phase, the structure of their inter-species co-abundance network was significantly altered, indicating that the ecological balance of GDM patients was not "healthier" after the diet intervention. Furthermore, we suggest that abnormal glucose regulation is associated with large network deviations, which could lead to the development of individualized microbiome-based therapies in the future. Our work highlights the importance of studying the microbiome from a network perspective to better understand the dynamic interactions among microorganisms in the community balance of the microbiome.

systems biology↗

bioRxiv2023

Collagen co-localised with macrovesicular steatosis for fibrosis progression in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a commonly occurring liver disease; however, its exact pathogenesis is not fully understood. The purpose of this study was to quantitatively evaluate the progression of steatosis and fibrosis by examining their distribution, morphology, and co-localisation in NAFLD animal models. qSteatosis showed a good correlation with steatosis grade (R: 0.823-0.953, P<0.05) and demonstrated high performance (area under the curve [AUC]: 0.617-1) in all six mouse models. Based on their high correlation with histological scoring, qFibrosis containing four shared parameters were selected to create a linear model that could accurately identify differences among fibrosis stages (AUC: 0.725-1). qFibrosis co-localised with macrosteatosis generally correlated better with histological scoring and had a higher AUC in all six animal models (AUC: 0.846-1). Quantitative assessment using second-harmonic generation/two-photon excitation fluorescence imaging technology can be used to monitor different types of steatoses and fibrosis progression in NAFLD models. The collagen co-localised with macrosteatosis could better differentiate fibrosis progression and might aid in developing a more reliable and translatable fibrosis evaluation tool for animal models of NAFLD.

pathology↗

bioRxiv2022

Single-cell Transcriptomic Analysis of Systemic Autoinflammatory Diseases with Anti-TNFα Therapy

Systemic autoinflammatory diseases (SAIDs) are a group of rare diseases characterized by recurrent or continuous inflammation, typically accompanied by genetic variants. Good responses to anti-TNF therapy were observed in SAIDs patients. However, the mechanisms underlying the disease flare and the response to TNF blocking therapy have not been fully elucidated. Here, we use single-cell RNA sequencing technology to describe the transcriptomic profile of PBMCs and PMNs in SAIDs patients both before and after anti-TNF treatment. We found that interferon responses are involved in the active phase of the disease. After anti-TNF therapy, we observed remission from clinical symptoms while unexpected elevation of TNF and IL-1, indicating that these inflammatory cytokines are not positively correlated with disease activity. Trajectory analysis showed that inhibition of macrophage differentiation, rather than reduction of the inflammatory cytokines, as the potential mechanism of anti-TNF treatment response in SAIDs.

immunology↗

bioRxiv2022

Mode of inhibition of RNase P by gambogic acid and juglone

The first step in transfer RNA (tRNA) maturation is the cleavage of the 5 end of precursor transfer RNA (pre-tRNA) catalyzed by ribonuclease P (RNase P). RNase P is either a ribonucleoprotein (RNP) complex with a catalytic RNA subunit or a protein-only RNase P (PRORP). In most land plants, algae, and Euglenozoa, PRORP is a single-subunit enzyme. There are currently no inhibitors of protein-only RNase P that can be used as tools for studying the biological function of this enzyme. Therefore, we screened for compounds that inhibit the activity of a model PRORP from A. thaliana organelles (PRORP1) using a high throughput fluorescence polarization (FP) cleavage assay. Two compounds, gambogic acid and juglone (5-hydroxy-1,4-naphthalenedione) that inhibit PRORP1 in the 1 M range were identified and analyzed. These compounds similarly inhibit human mtRNase P, a multi-subunit protein enzyme, and are 50-fold less potent against bacterial RNA-dependent RNase P. Biochemical measurements indicate that gambogic acid is a rapid-binding, uncompetitive inhibitor that targets the PRORP1-substrate complex while juglone acts as time-dependent inhibitor of PRORP1. X-ray crystal structures of PRORP1 in complex with juglone demonstrate the formation of a covalent complex with cysteine side chains on the surface of the protein. A model consistent with the kinetic data is that juglone binds to PRORP1 rapidly to form an inactive enzyme-inhibitor (EI) complex, and then undergoes a slow step to form an inactive covalent adduct with PRORP1. These inhibitors have the potential to be developed into tools to probe PRORP structure and function relationships.

biochemistry↗

bioRxiv2022

Biophysical analysis of Gaussia Luciferase bioluminescence mechanisms using a non-oxidizable coelenterazine.

Gaussia luciferase (GLuc 18.2kDa; 168 residues) is a marine copepod luciferase that emits a bright blue light when oxidizing coelenterazine (CTZ). It is a helical protein where two homologous sequential repeats form two anti-parallel bundles, each made of four helices. We previously identified a hydrophobic cavity as a prime candidate for the catalytic site, but Glucs fast bioluminescence reaction hampered a detailed analysis. Here, we used azacoelenterazine, a non-oxidizable coelenterazine analog, as a probe to investigate its binding mode to GLuc. Interestingly, the biochemical studies of GLuc inhibition by azacoelenterazine also led us to find that salt, and monovalent anions, are required for GLucs bioluminescence, which seems reasonable for a sea-dwelling creature. The NMR-based investigation, using chemical shift perturbations monitored by 15NH-HSQC, suggested that CTZ binds to residue in or near the hydrophobic cavity. Of note is that these NMR data are in line with a recent structural prediction of GLuc, hypothesizing that large structural changes occur in regions remote from the hydrophobic cavity upon the addition of CTZ. Interestingly, these results point toward a unique mode of catalysis to achieve CTZ oxidative decarboxylation.

biophysics↗

bioRxiv2022

The highly conserved RNA-binding specificity of nucleocapsid protein facilitates the identification of drugs with broad anti-coronavirus activity

The binding of SARS-CoV-2 nucleocapsid (N) protein to both the 5'- and 3'-ends of genomic RNA has different implications arising from its binding to the central region during virion assembly. However, the mechanism underlying selective binding remains unknown. Herein, we performed the high-throughput RNA-SELEX (HTR-SELEX) to determine the RNA-binding specificity of the N proteins of various SARS-CoV-2 variants as well as other {beta}-coronaviruses and showed that N proteins could bind two unrelated sequences, both of which were highly conserved across all variants and species. Interestingly, both these sequence motifs are virtually absent from the human transcriptome; however, they exhibit a highly enriched, mutually complementary distribution in the coronavirus genome, highlighting their varied functions in genome packaging. Our results provide mechanistic insights into viral genome packaging, thereby increasing the feasibility of developing drugs with broad-spectrum anti-coronavirus activity by targeting RNA binding by N proteins.

molecular biology↗

bioRxiv2022

Human iPSC-derived neuron of 16p11.2 deletion reveals haplotype-specific expression of MAPK3 and its contribution to variable NDD phenotypes

Recurrent proximal 16p11.2 deletion (16p11.2del) is risk factor of diverse neurodevelopmental disorders (NDDs) with variable penetrance. Although previous human induced pluripotent stem cell (hiPSC) models of 16p11.2del confirmed disrupted neuron development, it is not known which gene(s) at this interval are mainly responsible for the abnormal cellular phenotypes and how the NDD penetrance is regulated. After haplotype phasing of 16p11.2 region, we generated hiPSCs for two 16p11.2del families with distinct residual haplotypes and variable NDD phenotypes. We also differentiated the hiPSCs to cortical neural cells and demonstrated MAPK3 as a driver signal of 16p11.2 region contributing to the dysfunctions in multiple pathways related to neuron development, which leads to altered morphological or electrophysiological properties in neuron cells. Furthermore, residual haplotype-specific MAPK3 expression was identified in 16p11.2del neuron cells, associating MAPK3 down-expression with the minor allele of the residual haplotype. Ten SNPs of the residual haplotype are mapped as enhancer SNPs (enSNPs) of MAPK3, eight enSNPs were functionally validated by luciferase assays, implying enSNPs contribute to residual haplotype-specific MAPK3 expression via cis-regulation. Finally, the analyses of three different patient cohorts showed that the residual haplotype of 16p11.2del is associated with variable NDD phenotypes.

genetics↗

bioRxiv2022

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant

Among the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, molecular evidences for the detailed mechanism of S-mediated membrane fusion are missing. Here we reported the in situ structure and distribution of S on the authentic Delta variant, and discovered invagination in the distinctive Delta architecture. We also captured fusion snapshots from the virus-virus fusion events, provided structural evidences for Deltas attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant. In BriefCryo-ET of intact SARS-CoV-2 Delta variant revealed its distinctive architecture and captured snapshots of its membrane fusion in action.

biophysics↗

bioRxiv2022

SER: an R package to compute environmental regime over a certain time period

O_LIEnvironmental regime (or environmental legacy or historical legacy) is the environmental dynamic characteristics over a given (either long or short) time period, such as frequency of mean or extreme events and rate of change, which might be masked by using only contemporary variables. C_LIO_LIWe present SER, an R package for estimating environmental regimes for different environmental variables. Using the data included in the package, several examples are shown. C_LIO_LISER is suitable for any types of environmental variables e.g., nutrient concentration, light, dissolved oxygen. In addition, by changing the argument "days_bf", it is possible to compute environmental regimes in any interested time period, such as days, months or years. C_LIO_LIOur case study showed that inclusion of environmental regimes dramatically increased the explained variation of temporal {beta}-diversity and its components. Environmental regimes, particularly in a given time period, are expected to advance the "environment - community" relationships in ecological studies. In addition, they can be implemented in other subjects, e.g., social science, socioeconomics, epidemiology, with important applied implications. C_LI

ecology↗

bioRxiv2022

Omicron-specific mRNA vaccine elicits potent immune responses in mice, hamsters, and nonhuman primates

SARS-CoV-2 has infected more than 400 million people around the globe and caused millions of deaths. Since its identification in November 2021, Omicron, a highly transmissible variant, has become the dominant variant in most countries. Omicrons highly mutated spike protein, the main target of vaccine development, significantly compromises the immune protection from current vaccination. We develop an mRNA vaccine (SOmicron-6P) based on an Omicron-specific sequence. In mice, SOmicron-6P shows superior neutralizing antibodies inducing abilities to a clinically approved inactivated virus vaccine, a clinically approved protein subunit vaccine, and an mRNA vaccine (SWT-2P) with the same sequence of BNT162b2 RNA. Significantly, SOmicron-6P induces a 14.4[~]27.7-fold and a 28.3[~]50.3-fold increase of neutralizing activity against the pseudovirus of Omicron and authentic Omicron compared to SWT-2P, respectively. In addition, two doses SOmicron-6P significantly protects Syrian hamsters against challenge with SARS-CoV-2 Omicron variant and elicits high titers of nAbs in a dose-dependent manner in macaques. Our results suggest that SOmicron-6P offers advantages over current vaccines, and it will be helpful for those with weak immunity.

microbiology↗