Biology subjects

Jiang, L.

Publications and source records attributed to Jiang, L..

At least 199 records · Page 11Linked to original sources

bioRxiv2022

Metagenomics revealing molecular profiling of microbial community structure and metabolic capacity in Bamucuo, Tibet

We performed a survey of the microorganisms in Bamucuo, Tibet, resulting in 160,212 (soil) and 135,994 (water) contigs by shotgun metagenomic methods. We discovered 74 new bacterial species and reconstructed their draft genomes, which were obtained from the 75 reconstructed almost complete metagenomic assembly genomes (MAG) in the soil and water samples. Proteobacteria and Actinobacteria were found to be the most dominant bacterial phyla, while Euryarchaeota was the most dominant archaeal phylum. To our surprise, Pandoravirus salinus was found in the soil microbial community. We concluded that the microorganisms in Bamucuo fix carbon mainly through the 3-hydroxypropionic bi-cycle pathway. IMPORTANCEThe Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and the microorganisms there play vital ecological roles in the global biogeochemical cycle; however, detailed information on the microbial communities in QTP is still lacking, especially in high altitude areas above 4500 meters. This study, for the first time, characterized the microbial community composition and metabolic capacity in QTP high-altitude areas (with an altitude of 4,555 meters), confirmed that QTP is a huge and valuable resource bank in which more new non-resistant antibiotics and many other bioactive substances could be developed. In addition, the discovery of Pandoravirus salinus in the soil provides important information for further exploring this unique microorganism, and many draft genomes and the genome annotation information obtained in this study have laid the foundation for further in-depth study of the microbial ecology in Qinghai-Tibet Plateau.

microbiology↗

bioRxiv2021

Assessment of chimeric antigen receptor T (CAR-T) cytotoxicity by droplet microfluidics in vitro

Chimeric antigen receptor T (CAR-T) cells are cytotoxic T cells engineered to specifically kill cancer cells expressing specific target receptor(s). Prior CAR-T efficacy tests include CAR expression analysis by qPCR or ELISA, in vitro measurement of interferon-{gamma} (IFN{gamma}) or interleukin-2 (IL-2), and xenograft models. However, the in vitro measurements did not reflect CAR-T cytotoxicity, whereas xenograft models are low throughput and costly. Here we presented a robust in vitro droplet microfluidic assay for CAR-T cytotoxicity assessment. This method not only enabled assessment of CAR-T cytotoxic activity under different fluid viscosity conditions, but also facilitated measurement of CAR-T expansion and dissection of mechanism of action via phenotype analysis in vitro. Furthermore, our data suggested that label-free cytotoxicity analysis is feasible by acquiring data before and after treatment. Hence, this study presented a novel in vitro method for assessment of cellular cytotoxicity that could potentially be applied to any cell-kill-cell experiment with varying solvent composition.

cancer biology↗

bioRxiv2021

LKB1 Is Physiologically Required for Sleep from Drosophila to the Mouse

LKB1 is known as a master kinase for 14 kinases related to the adenosine monophosphate (AMP)-activated protein kinase (AMPK). Two of them (SIK3 and AMPK) have previously been implicated in sleep regulation. We generated loss-of-function (LOF) mutants for Lkb1 in both Drosophila and mice. Sleep was reduced in Lkb1-mutant flies and in flies with neuronal deletion of Lkb1. Sleep was reduced in mice after virally mediated reduction of Lkb1 in the brain. Electroencephalography (EEG) analysis showed that non-rapid eye movement (NREM) sleep and sleep need were both reduced in Lkb1-mutant mice. These results indicate that LKB1 plays a physiological role in sleep regulation conserved from flies to mice.

neuroscience↗

bioRxiv2021

Screening and selection of 21 novel microhaplotype markers for ancestry inference in ten Chinese Subpopulations

Genetic findings suggested that ethnolinguistically diverse populations in China harbor differentiated genetic structure and complex evolutionary admixture history, which provide the genetic basis and theoretical foundation for forensic biogeographical ancestry inference (BGAI). Forensic assays for BGAI among intracontinental eastern Eurasians were previously conducted mainly based on the SNPs or InDels. Microhaplotypes, as a set of closely linked SNPs within 200 base pairs, possess the advantages of both STR and SNP and have great potential in forensic ancestry inference. However, the developed forensic assay based on the ancestry informative microhaplotypes in the BGAI remained to be comprehensively explored, especially in China with enriching genetic diversity. Here, we described a new BGAI panel based on 21 novel identified ancestry informative microhaplotypes that focused on dissected finer-scale ancestry composition of Chinese populations. We initially screened all possible microhaplotypes with high Fst values among five East Asian populations and finally employed 21 candidate microhaplotypes in two multiplex SNaPshot assays. Forensic amplification efficiency and statistically/physically phased haplotypes of the 21 microhaplotypes were validated using both SNaPshot and massively parallel sequencing (MPS) platforms. Followingly, we validated the efficiency of these microhaplotypes for BGAI in 764 individuals from ten Chinese populations. Fine-scale ancestry source and ancestry proportion estimated by the principal component analysis (PCA), multidimensional scaling (MDS), phylogenetic tree and model-based STRUCTURE among worldwide populations and East Asians showed that our customized panel could provide a higher discrimination resolution in both continental population stratification and East Asian regional substructure. East Asian populations could be further classified into linguistically/geographically different intracontinental subpopulations (Tibeto-Burman, Tai-Kadai and others). Finally, we obtained a higher estimated accuracy using training and tested datasets in the microhaplotype-based panel than traditional SNP-based panels. Generally, the above results demonstrated that this microhaplotype panel was robust and suitable for forensic BGAI in Chinese populations, which not only provided a high discriminatory power for continental populations but also discriminated East Asians into linguistically restricted subpopulations.

genetics↗

bioRxiv2021

Dynamics of peripheral blood flow across sleep stages

Study ObjectivesPulse rate variability (PRV) derived from peripheral blood flow has been reported as a surrogate parameter for heart rate variability (HRV). However, there are currently no studies reporting systematic comparisons of PRV with HRV in a normal sleep state. Whether PRV can provide similar information regarding sleep stages remains unclear. Peripheral blood flow may also be modulated differently across sleep stages. Thus, we aimed to investigate blood flow dynamics and compare PRV with HRV across sleep stages to see if blood flow can provide further information about sleep stages. MethodsWe performed electrocardiography and simultaneously measured blood flow from the right index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 {+/-} 3.4 years) during one night of sleep. Time-domain, frequency-domain, and non-linear indices of PRV/HRV, and time- and frequencydomain blood flow parameters were calculated. ResultsFinger-PRV results showed similar patterns to HRV results for most parameters. Finger-blood flow parameters in the time and frequency domains also showed information about the different sleep stages. Further, both finger- and ear-blood flow results showed 0.2-0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation (of respiration) within this frequency band. ConclusionsThese results suggest that PRV can provide as much information as HRV for different sleep stages. Furthermore, the results show that blood flow + PRV could be more advantageous than HRV alone in the assessment of the sleep state and related autonomic nervous activity. Statement of SignificanceThe research provides comprehensive information on peripheral blood flow (BF) activity across sleep stages for the first time, as the major novelty of our work. The second contribution is a systematic study comparing BF-derived pulse rate variability (PRV) with heart rate variability across sleep stages in a normal sleep state. We believe that our work makes a significant contribution to the literature because it provides comprehensive information on the potential of BF+PRV as a new biomarker for assessing the sleep state. Further, this study contributes to developing a more convenient method of assessing the sleep state in the clinical and home/work setting.

physiology↗

bioRxiv2021

Comprehensive identification of fetal cis-regulatory elements in the human genome by single-cell multi-omics analysis

The regulatory programs driving early organogenesis in human is complex and still poorly understood. We performed parallel profiling of gene expression and chromatin accessibility to 28 human fetal tissue samples representing 14 organs in the first trimester. Collectively, we have generated 415,793 single-cell profiles. By integration analysis of transcriptome and chromatin accessibility, we detected 225 distinct cell types and 848,475 candidate accessible cis-regulatory elements (aCREs). By linking regulatory elements to their putative target genes, we identified not only 108,699 enhancers, but also 23,392 silencers elements. We uncovered thousands of genes regulated by both enhancers and silencers in an organ or cell-type-specific manner. Furthermore, our unique approach revealed a substantial proportion of distal DNA elements are transcribed CREs (tCREs), which show both open chromatin signal and transcription initiation activity of non-coding transcript. The landscape of fetal cis-regulatory elements facilitates the interpretation of the genetic variant of complex disease and infer the cell type of origin for cancer. Overall, our data provide a comprehensive map of the fetal cis-regulatory elements at single-cell resolution and a valuable resource for future study of human development and disease.

developmental biology↗

bioRxiv2021

Lin28a rejuvenates muscle stem cells via mitochondrial optimization

The well-conserved correlation between juvenility and tissue regeneration was first discussed by Charles Darwin. Ectopic Lin28 is known to play an important role in somatic reprogramming and tissue regeneration, but endogenous Lin28s role in tissue homeostasis and juvenility had remained unclear. Through lineage tracing, we found that a rare subset of muscle stem cells (MuSCs) expressing Lin28a can respond to acute injury by proliferating as Pax3+ or Pax7+ MuSCs, and contribute to all types of myofibers during muscle regeneration. Compared with conventional Pax7+ MuSCs, Lin28a+ MuSCs express more Pax3 and show enhanced myogenicity in vitro. In terms of the epigenetic clock, adult Lin28a+ MuSCs lie between adult Pax7+ MuSCs and embryonic Pax7+ myoblasts according to their DNA methylation profiles. We found that Lin28a+ MuSCs upregulate several embryonic limb bud mesoderm transcription factors and could maintain a juvenile state with enhanced stem cell self-renewal and stress-responsiveness in vitro and in vivo. When combined with telomerase and TP53 inhibition to biomimic mouse Lin28a+ MuSCs, we found that Lin28a can rejuvenate and dedifferentiate aged human primary myoblasts into engraftable, self-renewing MuSCs. Mechanistic studies revealed that Lin28a activated the HIF1A pathway by optimizing mitochondrial ROS (mtROS), thereby rejuvenating MuSC self-renewal and muscle regeneration. Our findings connect the stem cell factor Lin28, mtROS metabolism and stress response pathways to the process of stem cell rejuvenation and tissue regeneration.

cell biology↗

bioRxiv2021

Extracellular Fluid Flow Induces Shallow Quiescence through Physical and Biochemical Cues

The balance between cell quiescence and proliferation is fundamental to tissue physiology and homeostasis. Recent studies have shown that quiescence is not a passive and homogeneous state but actively maintained and heterogeneous. These cellular characteristics associated with quiescence were observed primarily in cultured cells under a static medium. However, cells in vivo face different microenvironmental conditions, particularly, under interstitial fluid flows distributed through extracellular matrices. Interstitial fluid flow exerts shear stress on cells and matrix strain, and results in continuous replacement of extracellular factors. In this study, by analyzing individual cells under varying fluid flow rates in microfluidic devices, we found that extracellular fluid flow alters cellular quiescence depth through flow-induced physical and biochemical cues. Specifically, increasing the flow rate drives cells to shallower quiescence and become more likely to reenter the cell cycle upon growth stimulation. Furthermore, we found that increasing shear stress or extracellular factor replacement individually, without altering other parameters, also results in shallow quiescence. We integrated the experimental results into a mathematical model to gain insight and predict the effects of varying extracellular fluid flow conditions on cellular quiescence depth. Our findings uncover a previously unappreciated mechanism that likely underlies the heterogeneous responses of quiescent cells for tissue repair and regeneration in physiological tissue microenvironments.

cell biology↗

bioRxiv2021

Germline Missense Variants in CDC20 Result in Aberrant Mitotic Progression and Familial Cancer

CDC20 is a co-activator of the anaphase promoting complex/cyclosome (APC/C) and is essential for mitotic progression. APC/CCDC20 is inhibited by the spindle assembly checkpoint (SAC), which prevents premature separation of sister chromatids and aneuploidy in daughter cells. Although overexpression of CDC20 is common in many cancers, oncogenic mutations have never been identified in humans. Using whole exome sequencing, we identified heterozygous missense CDC20 variants (L151R and N331K) that segregate with cancer in two families. Characterization of these mutants showed they retain APC/C activation activity but show reduced binding to BUBR1, a component of the SAC. Expression of L151R and N331K promoted mitotic slippage in HeLa cells and primary skin fibroblasts derived from carriers. CRISPR/Cas9 was used to generate mice carrying N331K. Homozygous mice carrying N331K were non-viable, however, heterozygotes displayed accelerated oncogenicity in Myc-driven cancers. These findings highlight an unappreciated role for CDC20 variants as tumor promoting genes in humans.

cancer biology↗

bioRxiv2021

DNA replication stress stratifies prognosis and enables exploitable therapeutic vulnerabilities of HBV-associated hepatocellular carcinoma: an in silico strategy towards precision oncology

BackgroundHepatitis B virus (HBV), the main risk factor for hepatocellular carcinoma (HCC) development, integrates into the host genome, causing genetic instability, which may trigger malignancies to exhibit chronic DNA replication stress, providing exploitable therapeutic vulnerabilities. Therefore, customizing prognostication approach and expanding therapeutic options are of great clinical significance to HBV-associated HCCs. MethodsA robust machine-learning framework was designed to develop a DNA replication stress-related prognostic index (PIRS) based on 606 retrospectively collected HBV-associated HCC cases. Molecular profiles and drug response of HCC cell lines were leveraged to predict therapeutic targets and agents for patients with high mortality risk. ResultsCompared with established population-based predictors, PIRS manifested superior performance for prognostic prediction in HBV-associated HCCs. Lower PIRS tightly associated with higher expression of HBV oncoproteins, activated immune/metabolism pathways and higher likelihood of responding to immunotherapy; while higher PIRS showed co-occurrence manner with elevated Ki-67 progression marker and cancer stemness, and significantly enriched in DNA replication stress, cell cycle pathways, chromatin remodeling regulons, and presented an immune-cold phenotype with unfavorable clinical outcome. Through large-scale in silico drug screening, four potential therapeutic targets (TOP2A, PRMT1, CSNK1D, and PPIH) and five agents including three topoisomerase inhibitors (teniposide, doxorubicin, and epirubicin) and two CDK inhibitors (JNJ-7706621 and PHA-793887) were identified for patients with high PIRS. ConclusionsOverall, PIRS holds potential to improve the population-based therapeutic strategies in HCC and sheds new insight to the clinical management for those HBV carriers; current analytic framework provides a roadmap for the rational clinical development of personalized treatment.

bioinformatics↗

bioRxiv2021

Comprehensive Analysis of Co-Mutations Identifies Cooperating Mechanisms of Tumorigenesis

Somatic mutations are one of the most important factors in tumorigenesis and are the focus of most cancer sequencing efforts. The co-occurrence of multiple mutations in one tumor has gained increasing attention as a means of identifying cooperating mutations or pathways that contribute to cancer.Using multi-omics, phenotypical, and clinical data from 29,559 cancer subjects and 1,747 cancer cell lines covering 78 distinct cancer types, we show that co-mutations are associated with prognosis, drug sensitivity, and disparities in sex, age, and race. Some co-mutation combinations displayed stronger effects than their corresponding single mutations. For example, co-mutation TP53:KRAS in pancreatic adenocarcinoma is significantly associated with disease specific survival (hazard ratio = 2.87, adjusted p-value = 0.0003) and its prognostic predictive power is greater than either TP53 or KRAS as individually mutated genes. Functional analyses revealed that co-mutations with higher prognostic values have higher potential impact and cause greater dysregulation of gene expression. Furthermore, many of the prognostically significant co-mutations caused gains or losses of binding sequences of RNA binding proteins or micro RNAs with known cancer associations. Thus, detailed analyses of co-mutations can identify mechanisms that cooperate in tumorigenesis.

cancer biology↗

bioRxiv2021

SUMO E2/E3 Enzyme Co-Recognize Substrates and Confers High Substrates Specificity

Although various technologies can determine protein-protein interaction affinity, Kd, current approaches require at least one interacting protein to be purified. Here, we present a development of high-throughput approach to determine protein interaction affinity for un-purified interacting proteins using quantitative FRET assay. We developed this approach first using SUMO E2 conjugating enzyme, Ubc9, and SUMO substrate, RanGap1c. The interaction affinities from two purified proteins and two unpurified proteins in the presence of BSA, bacterial extracts or two mixtures are all in excellent agreement with that obtained from the SPR measurement. We then applied this approach to determine the interaction affinities of SUMO E3 PIAS1 and Ubc9 with a SUMO substrate, influenza virus protein, NS1, and, for the first time, the SUMO E3 ligase-substrate interaction affinity is determined, which enables us to provide a kinetics explanation for the two-enzyme substrate recognition mode. In general, our studies allow high-throughput determination of protein interacting affinity without any purification, and both the approach and scientific discoveries can be applied to proteins that are difficult to be expressed in general. O_LIProtein interaction dissociation constant, Kd, determination without any protein purification; C_LIO_LICo-recognition of substrates by two enzymes in one reaction; C_LIO_LIPotential affinity improvement mechanism of substrate recognition revealed with kinetics parameters in vivo. C_LI

biochemistry↗

bioRxiv2021

Gene regulatory networks controlling temporal patterning, neurogenesis and cell fate specification in the mammalian retina.

Gene regulatory networks (GRNs), consisting of transcription factors and their target cis- regulatory sequences, control neurogenesis and cell fate specification in the developing central nervous system, but their organization is poorly characterized. In this study, we performed integrated single-cell RNA- and scATAC-seq analysis in both mouse and human retina to profile dynamic changes in gene expression, chromatin accessibility and transcription factor footprinting during retinal neurogenesis. We identified multiple interconnected, evolutionarily-conserved GRNs consisting of cell type-specific transcription factors that both activate expression of genes within their own network and often inhibit expression of genes in other networks. These GRNs control state transitions within primary retinal progenitors that underlie temporal patterning, regulate the transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirmed the prediction of this analysis that the NFI transcription factors Nfia, Nfib, and Nfix selectively activate expression of genes that promote late-stage temporal identity in primary retinal progenitors. We also used GRNs to identify additional transcription factors that promote (Insm1/2) and inhibit (Tbx3, Tcf7l1/2) rod photoreceptor specification in postnatal retina. This study provides an inventory of cis- and trans-acting factors that control retinal development, identifies transcription factors that control the temporal identity of retinal progenitors and cell fate specification, and will potentially guide cell-based therapies aimed at replacing retinal neurons lost due to disease.

neuroscience↗

bioRxiv2021

Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina

Extracellular vesicles (EVs) have great potential as novel drug carriers for the treatment of various diseases. These lipid bilayer vesicles are naturally abundant in mammalian tissues and circulation, can be loaded with therapeutic small molecule drugs, (si)RNA, proteins and CRISPR/Cas9, and may be engineered for retention by specific tissues. However, many questions remain on the optimal dosing, administration route, and pharmacokinetics of EVs. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available from larger animals. Here, we investigated the pharmacokinetics and biodistribution of Expi293F-derived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a non-human primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125-fold dose range. We report that EVs administered IV had markedly longer circulation times in plasma than previously reported in mice, and were detectable in cerebrospinal fluid (CSF) after 30-60 minutes. Already after one minute following IV administration, we observed EV uptake by PBMCs, most notably B-cells. EVs were detected in liver and spleen within one hour of IV administration. None of the IN doses resulted in readily detectable EV levels in plasma, CSF, or organs, suggesting that IN delivery of EVs in large animals including humans may require reconsideration or pretreatment approaches. Furthermore, EV circulation times strongly decreased after repeated IV administration, possibly due to immune responses and with clear implications for xenogeneic EV-based therapeutics. We hope that our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs.

pharmacology and toxicology↗

bioRxiv2021

Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis

Small cell lung cancer (SCLC) is a recalcitrant cancer featured with high metastasis. However, the exact cell type contributing to metastasis remains elusive. Using Rb1L/L/Trp53L/L mouse model, we identify the NCAMhiCD44lo/- subpopulation as SCLC metastasizing cell (SMC), which is progressively transitioned from non-metastasizing NCAMloCD44hi cell (Non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal an important role of SWI/SNF complex, and knockout of its central component, Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-Non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as key molecular switch in orchestrating SCLC phenotypic transition and metastasis.

cancer biology↗

bioRxiv2021

Dynamics of synthetic yeast chromosome evolution shaped by hierarchical chromatin organization

Synthetic genome evolution provides a dynamic approach to systematically and straightforwardly explore evolutionary processes. SCRaMbLE is an evolutionary system intrinsic to the synthetic yeast genome that can rapidly drive structural variations. Here, we detect over 260,000 rearrangement events after SCRaMbLEing of a novel yeast strain harboring 6 synthetic yeast chromosomes. Remarkably, we find that the rearrangement events exhibit a specific landscape of rearrangement frequency. We further reveal that the landscape is shaped by combinatorial effects of chromatin accessibility and spatial contact probability. The rearrangements tend to occur in 3D spatially proximal and chromatin-accessible regions. Enormous numbers of rearrangements by SCRaMbLE provide a driving force to potentiate directed genome evolution, and investigation of the rearrangement landscape offers mechanistic insights into the dynamics of genome evolution.

synthetic biology↗

bioRxiv2021

The molecular mechanism of cytoadherence to placenta or tumor cells through VAR2CSA from Plasmodium falciparum

Pregnancy Associated Malaria (PAM) threatens more than one million pregnant women and their infants in endemic regions due to poor outcomes. VAR2CSA plays a vital role in the cytoadherence of infected erythrocytes (IEs) to placenta against immuno-clearance via binding to Chondroitin sulfate A (CSA), which is displayed mostly on the surface of placental or tumor cells. In this study, we determined the cryo-EM structures of VAR2CSA ectodomain and its complex with CSA at a resolution of 3.6 [A] and 3.4 [A], respectively and revealed that CSA binding induces significant conformational change for ligand accommodation. Beyond structural studies, we generated VAR2CSA fragments and mutation and evaluated their binding activity to either isolated CSA or placental and tumor cell line using multi-disciplinary techniques. The results showed that 9-site mutation in DBL2X abolished the CSA binding activity and also disrupted its binding to both placental and tumor cells. Overall, our work clearly elucidated the molecular mechanism of cytoadherence to placental or tumor cells through VAR2CSA. Which may facilitate new PAM vaccine development and improve the drug delivery systems targeting both placenta and tumors.

biophysics↗

bioRxiv2021

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titers of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titers in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

immunology↗