Biology subjects

Zhu, M.

Publications and source records attributed to Zhu, M..

At least 91 records · Page 5Linked to original sources

bioRxiv2024

Screening and assessment of functional variants by regulatory features from epigenomic data in livestock species

BackgroundUnderstanding the functional impact of genetic variants is essential for advancing animal genomics and improving livestock breeding. Variants that disrupt transcription factor (TF) motifs provide a means to assess functional potential, but the lack of TF ChIP-seq data for farm animals presents a challenge. ResultsTo address this, we curated nearly 900 epigenomic datasets from 10 farm animal species and annotated eight regulatory regions to assess how variants affect TF motifs. Over 127 million candidate functional variants were classified into five functional confidence categories across the species. Variants with high confidence were enriched in eQTLs and trait-associated SNPs, showing greater potential to affect gene expression and phenotypes. Incorporating these functional variants into genomic prediction models improved the accuracy of Estimated Breeding Values (EBVs). Active variants also revealed trait-related tissues, and single-cell RNA sequencing (scRNA-seq) identified the cell types most associated with production traits. To facilitate research, we developed the Integrated Functional Mutation (IFmut) platform, enabling users to explore variant functions easily. Our study provides a flexible platform and resource for studying genomic variation in farm animals, setting a new standard for research and breeding strategies. ConclusionThe results indicated that evaluating functional potential by annotating and categorizing variants that interfere with transcription factor motifs can help elucidate changes in gene expression and phenotype. By focusing on high-confidence variants enriched in eQTL and trait-associated SNPs, it improves the accuracy of genomic predictions in research and breeding strategies.

genomics↗

bioRxiv2024

Dispensable regulation of brain development and myelination by Serpina3n

Serine protease inhibitor clade A member 3n (Serpina3n) or its human orthologue SERPINA3 is a secretory immune-related molecule produced primarily in the liver and brain under homeostatic conditions and upregulated in response to system inflammation. Yet it remains elusive regarding its cellular identity and physiological significance in the development of the postnatal brain. Here, we reported that oligodendroglial lineage cells are the major cell population expressing Serpina3n protein in the postnatal murine CNS. Using loss-of-function genetic tools, we found that Serpina3n conditional knockout (cKO) from Olig2-expressing cells does not significantly affect cognitive and motor functions in mice. Serpina3n depletion does not appear to interfere with oligodendrocyte differentiation and developmental myelination nor affects the population of other glial cells and neurons in vivo. Together, these data suggest that the immune-related molecule Serpina3n plays a minor role, if any, in regulating neural cell development in the postnatal brain under homeostatic conditions. We found that Serpina3n is significantly upregulated in response to oxidative stress, and it potentiates oxidative injury and cell senescence of oligodendrocytes. Our data raise the interest in pursuing its functional significance in the CNS under disease/injury conditions.

neuroscience↗

bioRxiv2024

Disconnection Between Microvascular Damage and Neurodegeneration in Early Diabetic Retinopathy

AimDiabetic retinopathy (DR) is a common complication of diabetes mellitus and can result in vision loss. Early clinically diagnosed signs of DR are linked to vascular damage, impacting on the neural retina typically at later stages. However, vascular changes and potential effects on neural cells before clinical diagnosis of DR are less understood. MethodsTo learn more about the earliest stages of DR we studied postmortem retina from diabetic donors who did not have clinical DR. Histological phenotyping and quantitative analysis were carried out on retina from 14 donors (3 controls, 10 diabetics, and 1 DR case) to examine capillary loss in the deeper vascular plexus (DVP) and the superficial vascular plexus (SVP) of the retinal vasculature and to study effects on the neural retina. ResultThe advanced DR case exhibited profound vascular and neural damage as expected, whereas none of the ten randomly selected diabetic donors had any DR signs that would have been diagnosed clinically. Within that group, two showed very minor capillary dropout in the SVP, whilst in the remaining diabetic cases the SVP was indistinguishable from the controls. In contrast, over half of the diabetic retinas showed capillary dropout in the DVP and increased capillary diameter. Furthermore, a pan retinal loss of inner nuclear layer cells was observed in those diabetics with capillary dropout compared to the controls (p<0.05), but there was no local spatial correlation between neural cell loss and capillary dropout. ConclusionsOur study has established a novel histological biomarker for diabetes related tissue damage at the earliest stages of DR in human postmortem retina, which appears to be common in people with diabetes before DR can be clinically diagnosed. Furthermore, the spatial mismatch between local capillary dropout and the diffuse neural loss in the INL suggests that at this very early stage of DR, microvascular loss may not causally be directly connected to neurodegeneration and that diabetes may affect the two readouts independently. RESEARCH IN CONTEXTWhat is already known about this subject? O_LIEarly DR is currently clinically defined by visible microvascular changes. C_LIO_LITests of retinal function in people with diabetes imply neuroretinal impairments in early DR. C_LIO_LIClinical imaging in people with diabetes suggests reduced perfusion in the deep retinal vasculature plexus. C_LI What is the key question? (one bullet point only; formatted as a question) O_LIHow does retinal microvascular damage relate to neuronal damage? C_LI What are the new findings? O_LIWe have developed a sensitive histological biomarker for microvascular damage in postmortem retinal tissue. C_LIO_LIEarly vascular changes in the deeper plexus occur in diabetes even in the absence of manifest DR. C_LIO_LINeurodegenerative changes are distributed throughout the retina in diabetes and do not spatially correlate with microvascular nonperfusion. C_LI How might this impact on clinical practice in the foreseeable future? O_LIDeeper plexus perfusion can be a useful early biomarker to assess DR. C_LI

pathology↗

bioRxiv2024

Using split protein reassembly strategy to optically control PLD enzymatic activity

Phospholipase D (PLD) and phosphatidic acid (PA) play a spatio-temporal role in regulating diverse cellular activities. Although current methodologies enable optical control of the subcellular localization of PLD and by which influence local PLD enzyme activity, the overexpression of PLD elevates the basal PLD enzyme activity and further leads to increased PA levels in cells. In this study, we employed a split protein reassembly strategy and optogenetic techniques to modify superPLD (developed by Jeremy Baskin group). We splited this variants into two HKD domains and fused these domains with optogenetic and chemogenetic elements and by which we achieved control of the two HKD interaction and then restored the PLD enzymatic activity.

cell biology↗

bioRxiv2024

Hexose transporters CsHT3/16 involved in post-phloem transport and affected cucumber fruit development

Hexoses are crucial for plant growth and fruit development. However, the role of hexose transporters in post-phloem sugar transport and maintenance of cellular sugar homeostasis in rapidly growing fruits, such as cucumber, is not yet fully understood. To clarify the impact of hexose transporters in cucumber fruits, we conducted systematic analyses of their tissue expression, localization, transport characteristics and physiological functions. The study revealed that CsHT3, CsHT12 and CsHT16 are the primary hexose transporter genes expressed in cucumber fruit. During the ovary and young fruit stages, CsHT3 and CsHT16 were located in the SE/CC system, but as the cucumber fruit developed and expanded, both transporters shifted to phloem parenchyma cells. The knock-out mutants of CsHT16 display shorter fruits with a larger circumference, likely due to impaired homeostasis of sugars and hormones. Simultaneously reducing the expression of CsHT3, CsHT12 and CsHT16 leads to decreased fruit size. Conversely, overexpression of CsHT3 results in increased fruit size and higher fruit sugar levels. Our data suggest that CsHT16 plays an important role in maintaining sugar homeostasis to shape the fruit, while CsHT3, CsHT12 and CsHT16 together determine the carbohydrates requirement of the enlarged cucumber fruit.

physiology↗

bioRxiv2024

Liver cancer initiation is dependent on metabolic zonation but decoupled from premalignant clonal expansion

The origin of cancer is poorly understood because cells that obtain truncal mutations are rarely fate mapped in their native environments. A defining feature of the liver is zonation, or the compartmentalization of metabolic functions in hepatocytes located in distinct regions of the lobule 1. However, it is unknown if cancers develop in some zones but not others, and if there are metabolic determinants of cancer risk that track with cellular position. To study cancer initiation, we examined the effect of activating mutations in Ctnnb1 and loss of function mutations in Arid2, two of the most commonly co-mutated genes in hepatocellular carcinoma (HCC) 2. We exploited glutamine synthetase (GS) as a faithful fate mapping marker of Ctnnb1 mutant hepatocytes. By introducing mutations in distinct zones in a mosaic fashion, we showed that position and metabolic context regulate clone expansion. Mutant clones were maintained in zone 1 but largely outcompeted in zone 3. Paradoxically, clonal maintenance was anti-correlated with cancer initiation, as zone 3 mutant livers showed increased tumorigenesis. To define mechanisms, we individually deleted eleven zone specific genes in HCC mouse models, revealing that Gstm2 and Gstm3 were required for efficient HCC initiation in zone 3. These data indicate that liver cancer initiation is dependent on zonation but independent of clonal expansion.

cancer biology↗

bioRxiv2023

Vaginal Lactobacillus fatty acid response mechanisms reveal a novel strategy for bacterial vaginosis treatment

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related species, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the human vaginal microbiota and sequesters OA in a derivative form that only ohyA-harboring organisms can exploit. Finally, OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro model of BV, suggesting a novel approach for treatment.

microbiology↗

bioRxiv2023

Tissue stiffness mapping by light sheet elastography

Tissue stiffness plays a crucial role in regulating morphogenesis. The ability to measure and monitor the dynamic progression of tissue stiffness is important for generating and testing mechanistic hypotheses. Methods to measure tissue properties in vivo have been emerging but present challenges with spatial and temporal resolution especially in 3D, by their reliance on highly specialised equipment, and/or due to their invasive nature. Here, introduce light sheet elastography, a noninvasive method that couples low frequency shear waves with light sheet fluorescence microscopy by adapting commercially available instruments. With this method, we achieved in toto stiffness mapping of organ-stage mouse and zebrafish embryos at cellular resolution. Versatility of the method enabled time-lapse stiffness mapping during tissue remodelling and of the beating embryonic heart. This method expands the spectrum of tools available to biologists and presents new opportunities for uncovering the mechanical basis of morphogenesis.

bioengineering↗

bioRxiv2023

Stimulus-reward contingencies drive long-lasting alterations in neocortical somatostatin inhibition during learning

Learning involves the association of discrete events in the world to infer causality, likely through a cascade of changes at input- and target-specific synapses. Transient or sustained disinhibition may initiate cortical circuit plasticity important for association learning, but the cellular networks involved have not been well-defined. Here we show that sensory association learning drives a durable, target-specific reduction in inhibition from somatostatin (SST)-expressing GABAergic neurons onto pyramidal (Pyr) neurons in superficial but not deep layers of mouse somatosensory cortex. Critically, SST-output was not altered when stimulus and rewards were unpaired, indicating that these neurons are not modified by sensory input alone. Depression of SST output onto Pyr neurons could be phenocopied by chemogenetic suppression of SST activity outside of the training context. Thus, neocortical SST neuron output is persistently modified by convergent sensory and reinforcement signals to selectively disinhibit superficial layers of sensory neocortex during learning.

neuroscience↗

bioRxiv2023

Application of slow-controlled release fertilizer coordinates the carbon flow in carbon-nitrogen metabolism to effect rice quality

Slow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm-2 and 11.0 t hm-2) and grain quality reaching the level of CK group. The sufficient nitrogen supply in both the PCU and BBF groups during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon-nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon-nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon-nitrogen metabolism to enhance rice quality.

plant biology↗

bioRxiv2023

A precise IDMS-based method for absolute quantification of phytohemagglutinin, a major antinutritional component in common bean

Phytohemagglutinin (PHA), a natural tetramer comprising PHA-E and PHA-L subunits that preferentially bind to red and white blood cells, respectively, constitutes a significant antinutritional and allergenic factor in common bean seeds. The accurate measurement of PHA content is a prerequisite for ensuring food safety inspections and facilitating genetic improvements in common bean cultivars with reduced PHA levels. Currently, mainstream methods for PHA quantification involve hemagglutination assays and immunodetection, but these methods often require fresh animal blood and lack specificity and accuracy. In this study, we present a novel LC-MS/MS-based method for PHA quantification, leveraging the advantages of isotope dilution mass spectrometry (IDMS). Two signature peptides each for PHA-E and PHA-L, along with a common signature peptide, were identified and employed for quantification, allowing differentiation between PHA-E and PHA-L subunits. The incorporation of amino acid analysis-isotope dilution mass spectrometry (AAA-IDMS) enabled precise determination of the synthetic signature peptides purity during measurement, enhancing metrological accuracy. In addition, the TCA-acetone protocol was established as the optimized method for total protein extraction from dry bean seeds. Quantitative analysis of PHA-E and PHA-L subunits in six common bean varieties using the developed method demonstrated excellent linearity (r > 0.999), sensitivity (limit of detection and quantitation as low as 2.32 ng/mg and 7.73 ng/mg, respectively), recovery (94.18-104.47%), and repeatability (relative standard deviation < 3.45%). This method has the potential to serve as a standard for measuring PHA contents in common beans and other agricultural products containing PHA.

biochemistry↗

bioRxiv2023

Lithocholic acid phenocopies rejuvenating and life-extending effects of calorie restriction

Calorie restriction (CR) is a dietary intervention to promote health and longevity. CR causes various metabolic changes in both the production and circulation of metabolites; however, it remains unclear which of the changed metabolite(s) can account for the physiological benefits of CR. Through metabolomic analysis of metabolites undergoing abundance changes during CR and subsequent functional validation, we found that lithocholic acid (LCA) is the only metabolite that alone can recapitulate the effects of CR, including activation of AMPK and the rejuvenating effects of muscle regeneration, grip strength and running capacity in mice. Interestingly, LCA also activates AMPK and exerts life- and health-extending effects in Caenorhabditis elegans and Drosophila melanogaster, indicating that these animal models are able to transmit the signalling of LCA once administered. Knockout of AMPK abrogates LCA-induced phenotypes, in nematodes and flies, as well as in mice. Together, we have identified that administration of the CR-upregulated metabolite LCA alone can confer anti-ageing benefits to metazoans, in an AMPK-dependent manner.

physiology↗

bioRxiv2023

Tradeoff Between Speed and Robustness in Primordium Initiation Mediated by Auxin-CUC1 Interaction

Robustness is the reproducible development of a phenotype despite stochastic noise. It often involves tradeoffs with other performance metrics, but the mechanisms underlying such tradeoffs were largely unknown. An Arabidopsis flower robustly develops four sepals from four precisely positioned auxin maxima. The development related myb-like 1 (drmy1) mutant generates noise in auxin signaling that disrupts robustness in sepal initiation. Here, we found that increased expression of CUP-SHAPED COTYLEDON1 (CUC1), a boundary specification transcription factor, in drmy1 underlies this loss of robustness. CUC1 surrounds and amplifies stochastic auxin noise in drmy1 to form variably positioned auxin maxima and sepal primordia. Removing CUC1 from drmy1 provides time for noisy auxin signaling to resolve into four precisely positioned auxin maxima, restoring robust sepal initiation. However, removing CUC1 decreases auxin maxima intensity and slows down sepal initiation. Thus, CUC1 increases morphogenesis speed but impairs robustness against auxin noise. Further, using a computational model, we found that the observed phenotype can be explained by the effect of CUC1 in repolarizing PIN FORMED1 (PIN1), a polar auxin transporter. Lastly, our model predicts that reducing global growth rate improves developmental robustness, which we validated experimentally. Thus, our study illustrates a tradeoff between speed and robustness during development.

developmental biology↗

bioRxiv2023

Bacillus velezensis HBXN2020 alleviates Salmonella Typhimurium-induced colitis by improving intestinal barrier integrity and reducing inflammation

Bacillus velezensis is a species of Bacillus that has been widely investigated because of its broad-spectrum antimicrobial activity. However, most studies on Bacillus velezensis have focused on the biocontrol of plant diseases, with few reports on antagonizing Salmonella Typhimurium infections. In this investigation, it was discovered that Bacillus velezensis HBXN2020, which was isolated from healthy black pigs, possessed strong anti-stress and broad-spectrum antibacterial activity. Importantly, Bacillus velezensis HBXN2020 did not cause any adverse side effects in mice when administered at various doses (1 x 107, 1 x 108, and 1 x 109 CFU) for 14 d. Supplementing Bacillus velezensis HBXN2020 spores, either as a curative or preventive measure, dramatically reduced the levels of Salmonella Typhimurium ATCC14028 in the mices feces, ileum, cecum, and colon, as well as the disease activity index (DAI), in a model of infection caused by this pathogen in mice. Additionally, supplementing Bacillus velezensis HBXN2020 spores significantly regulated cytokine levels (TNF-, IL-1{beta}, IL-6, and IL-10) and maintained the expression of tight junction proteins and mucin protein. Most importantly, adding Bacillus velezensis HBXN2020 spores to the colonic microbiota improved its stability and increased the amount of beneficial bacteria (Lactobacillus and Akkermansia). All together, Bacillus velezensis HBXN2020 can improve intestinal microbiota stability and barrier integrity and reduce inflammation to help treat infection by Salmonella Typhimurium.

microbiology↗

bioRxiv2023

An NMR-guided approach for identifying co-factors in boosting the Pfu DNA polymerase

With rapid developments of emerging technologies like synthetic biology, the demand for DNA polymerases with superior activities including higher thermostability and processivity has increased significantly. Thus, rational optimization of the performance of DNA polymerase is of great interest. Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique used for studying protein structure and dynamics. It provides the atomic resolution information of enzymes under its functional solution environment to reveal the active sites (hot spots) of the enzyme, which could be further used for optimizing the performance of enzymes. In our previous work, we identified hot spot residues of Pfu DNA polymerase (Pfu pol). We aim to employ these binding hot spots to screen for co-factors of Pfu pol, particularly targeting those molecules exhibiting weak intermolecular interactions. To validate this concept, we first demonstrated the feasibility of utilizing hot spot residues as screening probes for auxiliary factors by employing the well-characterized Tween-20 as a model system. Employing these hot spots as probes, two new co-factors, the heat shock protein TkHSP20 from Thermococcus Kodakaraensis and the chemical chaperone L-arginine, are identified to interact with Pfu pol to boost its performance in amplifying long DNA fragments by enhancing the thermal stability and the processivity of the Pfu pol. This NMR-based approach requires no prior assignment information of target enzymes, guiding the rational exploration of novel co-factors for Pfu pol. Moreover, our approach is not dependent on structural data or bioinformatics. Therefore, it has significant potential for application in various enzymes to expedite the progress in enzyme engineering.

molecular biology↗

bioRxiv2023

Untangling the Role of Pathobionts from Bacteroides Species in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) arise from a convergence of underlying genetic susceptibility, environmental factors, and shifts in gut microbiota function and membership. Although the latter may trigger and contribute to IBD, there is little consensus on a specific causative pathogen. In this study, we demonstrate that commensal Bacteroides fragilis strains from ulcerative colitis (UC) patients before and during the development of ileal pouchitis engraft and promote colitis in specific pathogen free (SPF) IL-10 deficient (IL-10-/-) mice, but not in wild type SPF mice or when mono-associated in germ free mice. The colitis in IL-10-/- mice was also associated with significant alterations in commensal microbiota potentially important for maintaining intestinal and immune homeostasis. UC pouchitis B. fragilis also engrafts in DSS-induced colitis in WT SPF mice, indicating a fitness advantage under conditions of mucosal inflammation over other commensals in the gut microbiota. These findings show that gut inflammation promotes the expansion and fitness of UC-derived Bacteroides species that is associated with changes in the SPF gut microbiota and may be promote colitis in genetically susceptible hosts. ImportanceThis study supports the notion that human inflammatory bowel diseases arise from the emergence of indigenous pathobionts in genetically-prone subjects. Colitis-promoting pathobionts are well-suited to establish themselves in the host inflammatory environment and outcompete endogenous microbiota. Once engrafted, the pathobiont can further aggravate inflammation in a genetically-susceptible host. Such complex interplay among several factors creates a vicious pro-inflammatory cycle and promotes disease development. These findings are consistent with our previous clinical observation that B. fragilis, an otherwise low-abundance commensal species, expands prior to the development of UC pouchitis. We believe these findings are relevant to the pathogenesis of UC pouchitis and possibly human inflammatory bowel diseases in general, underscoring the role of commensal to pathobiont transitions, rather than classical pathogens, in promoting and exacerbating the onset of human IBD.

microbiology↗

bioRxiv2023

Architecture and activation of human muscle phosphorylase kinase

The study of phosphorylase kinase (PhK)-regulated glycogen metabolism has contributed to the fundamental understanding of protein phosphorylation. Here we present the high-resolution cryo-electron microscopy structures of human muscle PhK. The 1.3-megadalton PhK 4{beta}4{gamma}4{delta}4 hexadecamer consists of a tetramer of tetramer, wherein four {beta}{gamma}{delta} modules are connected by the central {beta}4 scaffold. The - and {beta}-subunits possess glucoamylase-like domains, but exhibit no detectable enzyme activities. The -subunit serves as a bridge between the {beta}-subunit and the {gamma}{delta} subcomplex, and facilitates the {gamma}-subunit to adopt an autoinhibited state. Ca2+-free calmodulin ({delta}-subunit) binds to the {gamma}-subunit in a compact conformation. Upon binding of Ca2+, a conformational change occurs, allowing for the de-inhibition of the {gamma}-subunit through a spring-loaded mechanism. We also reveal an ADP-binding pocket in the {beta}-subunit, which plays a role in allosterically enhancing PhK activity. These results provide unprecedented molecular insights of this important kinase complex.

biochemistry↗

bioRxiv2023

XBB.1.5 Spike Protein COVID-19 Vaccine Induces Broadly Neutralizing and Cellular Immune Responses Against EG.5.1 and Emerging XBB Variants

Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces cross-neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4+ T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023-2024 COVID-19 vaccination campaign.

immunology↗