Biology subjects

Cao, Y.

Publications and source records attributed to Cao, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2024

A community-oriented, data-driven resource to improve protocol design for cardiac modelling from human pluripotent stem cells

Protocol design and benchmarking is central to optimising model development using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs). By applying data mining to decades of research and hundreds of peer reviewed studies, we evaluate how protocol variables associate with common properties of cardiac functional and physiological maturation. This resource is publicly accessible through CMPortal, a community-oriented website that provides data-driven tools for researchers to navigate leverage decades of knowledge for benchmarking protocol designs and outcomes for their dedicated applications in developmental biology, disease modelling, and drug screening.

developmental biology↗

bioRxiv2024

Structural and molecular basis of the epistasis effect in enhanced affinity between SARS-CoV-2 KP.3 and ACE2

The recent emergence of SARS-CoV-2 variants KP.2 and KP.3 has been marked by mutations F456L/R346T and F456L/Q493E, respectively, which significantly impact the viruss interaction with human ACE2 and its resistance to neutralizing antibodies. KP.3, featuring F456L and Q493E, exhibits a markedly enhanced ACE2 binding affinity compared to KP.2 and the JN.1 variant due to synergistic effects between these mutations. This study elucidated the structures of KP.2 and KP.3 RBD in complex with ACE2 using cryogenic electron microscopy (Cryo-EM) and decipher the structural and thermodynamic implications of these mutations on receptor binding by molecular dynamics (MD) simulations, revealing that F456L mutation facilitates a more favorable binding environment for Q493E, leading to stronger receptor interactions which consequently enhance the potential for incorporating additional evasive mutations. These results underscore the importance of understanding mutational epistatic interactions in predicting SARS-CoV-2 evolution and optimizing vaccine updates. Continued monitoring of such epistatic effects is crucial for anticipating new dominant strains and preparing appropriate public health responses.

molecular biology↗

bioRxiv2024

Cholinergic signaling differentially regulates song premotor circuits to stabilize songs in songbirds

Cholinergic modulation plays an important role in motor skill performance, including vocal control. In songbirds, song motor nucleus RA simultaneously receives inputs from song nuclei HVC and LMAN, and then its projection neurons (RAPNs) generate song motor control output. Using electrophysiological and pharmacological methods, we found that cholinergic signaling can enhance song stability by reducing HVC-RAPN excitatory synaptic transmission in adult male zebra finches, mediated by mAChRs. Although nAChRs are not effective overall, cholinergic signaling can also decrease LMAN-RAPN excitatory synaptic transmission induced by electrical stimulation via nAChRs, suggesting the potential role of cholinergic regulation in song behavior through LMAN-RA pathway. On the contrary, in adult female zebra finches, only LMAN-RAPN synaptic transmission was reduced by cholinergic signaling via mAChRs. The role of differential cholinergic regulation of song premotor circuits in songbirds singing provides insights into the neural control mechanism of motor skill performance.

neuroscience↗

bioRxiv2024

An automated microfluidic platform for toxicity testing based on Caenorhabditis elegans

Humans are frequently exposed to a multitude of chemicals daily, necessitating efficient methods for rapidly assessing toxicity and potential health risks. Microfluidics has shown promise as an intelligent tool for rapid compound testing, owing to its flexibility in integrating with automated devices. The article introduces an automated microfluidic platform, based on Caenorhabditis elegans (C. elegans), designed for chemical toxicity testing. This platform consists of three modules - worm culture, monitoring, and image analysis - which enable automated worm culturing, drug delivery, periodic monitoring, and automated phenotypic analysis. Researchers have designed a bridged microfluidic chip that permits worms to move freely during experiments and established an economical monitoring module for long-term tracking and periodic imaging. Furthermore, they have developed an automated image analysis algorithm to automatically determine worm bending frequency. The platform was subsequently utilized for long-term toxicological assessments of the organophosphate pesticide and environmental pollutants. Results indicated that the platform can effectively evaluate the general and developmental impacts of chemicals. The automated microfluidic worm analysis platform holds significant potential for applications in drug safety assessmentand drug screening research, contributing to human health and industry advancement.

bioengineering↗

bioRxiv2024

Inflammatory Signatures of Microglia in the Mouse Model of Corticosterone-Induced Depression

Microglia-mediated inflammation has been recognized as a key feature of major depressive disorder. Although hypercortisolemia commonly occurs in depressed patients and can be predictive of treatment response, how chronic exposure to this stress hormone influences microglia is incompletely characterized. Here, we exploited a standard mouse model of depressive-like behaviors induced by peripheral administration of corticosterone. Microglia in the prefrontal cortex of mice were profiled by bulk RNA sequencing, which exhibited the up-regulation of inflammatory markers. In addition, single-cell RNA sequencing identified distinct molecular patterns of microglial responses. Moreover, we revealed the elevation of Pu.1 and Irf8, the two central transcription factors governing microglia-mediated inflammation, in the prefrontal cortex and hippocampus of corticosterone-treated mice, which was similarly observed in the single-nucleus RNA sequencing dataset of depressed patients microglia. These results have established inflammatory signatures of microglia in the mouse model recapitulating hypercortisolemia-related depression, providing new insights into diagnostic and therapeutic strategies.

neuroscience↗

bioRxiv2024

The barley MLA13-AVRA13 heterodimer reveals principles for immunoreceptor recognition of RNase-like powdery mildew effectors

Co-evolution between cereals and pathogenic grass powdery mildew fungi is exemplified by sequence diversification of an allelic series of barley resistance genes encoding Mildew Locus A (MLA) nucleotide-binding leucine-rich repeat (NLR) immunoreceptors with a N-terminal coiled-coil domain (CNLs). Each immunoreceptor recognises a matching, strain-specific powdery mildew effector encoded by an avirulence gene (AVRa). We present here the cryo-EM structure of barley MLA13 in complex with its cognate effector AVRA13-1. The effector adopts an RNase-like fold when bound to MLA13 in planta, similar to crystal structures of other RNase-like AVRA effectors purified from E. coli. AVRA13-1 interacts via its basal loops with MLA13 C-terminal leucine rich repeats (LRRs) and the central winged helix domain (WHD). Co-expression of structure-guided MLA13 and AVRA13-1 substitution variants show that the receptor-effector interface plays an essential role in mediating immunity-associated plant cell death. Furthermore, by combining structural information from the MLA13-AVRA13-1 heterocomplex with sequence alignments of other MLA receptors, we designed a single amino acid substitution in MLA7 that enables expanded effector detection of AVRA13-1 and the virulent variant AVRA13-V2. In contrast to the pentameric conformation of previously reported effector-activated CNL resistosomes, MLA13 was purified and resolved as a stable heterodimer from an in planta expression system. Our study suggests that the MLA13-AVRA13-1 heterodimer might represent a CNL output distinct from CNL resistosomes and highlights opportunities for the development of designer gain-of-function NLRs.

plant biology↗

bioRxiv2024

HIV broadly neutralizing antibody escapability drives the therapeutic efficacy of vectored immunotherapy

Broadly neutralizing antibodies (bNAbs) have shown promise for prevention and treatment of HIV. Potency and breadth measured in vitro are often used as predictors of clinical potential; however, human studies demonstrate that clinical efficacy of bNAbs can be undermined by both pre-existing and de novo resistance. Here we find that HIV-infected humanized mice receiving bNAbs delivered via AAV as Vectored ImmunoTherapy (VIT) can be used to identify antibody escape paths, which are largely conserved for each bNAb. Path selection, and consequent therapeutic success, is driven by the fitness cost and resistance benefit of emerging mutations. Applying this framework, we independently modulated bNAb resistance or the fitness cost of escape mutants, resulting in enhanced efficacy of VIT. This escape path analysis successfully explains the therapeutic efficacy of bNAbs, and enables a tractable means of quantifying and comparing the potential for viral escape from therapeutics in vivo. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/603156v4_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@180c86borg.highwire.dtl.DTLVardef@1e6108dorg.highwire.dtl.DTLVardef@148bac7org.highwire.dtl.DTLVardef@1de93ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

QuickFit: A high-throughput RT-qPCR-based assay to quantify viral growth and fitness in vitro

The quantification of viral growth rates is key to understanding evolutionary dynamics and the potential for mutants to escape antiviral drugs. Defining evolutionary escape paths and their impact on viral fitness allows for the development of drugs that are resistant to escape. In the case of HIV, combination antiretroviral therapy can successfully prevent or treat infection, but it relies on strict adherence to prevent escape. Here, we present a method that enables the quantification of viral fitness termed QuickFit, which employs large numbers of parallel viral cultures to accurately measure growth rates. QuickFit consistently recapitulated HIV growth measurements obtained by traditional approaches but with significantly higher throughput and lower error. This method represents a promising tool for rapid and consistent evaluation of viral fitness.

microbiology↗

bioRxiv2024

Omicron-specific ultra-potent SARS-CoV-2 neutralizing antibodies targeting the N1/N2 loop of Spike N-terminal domain

A multitude of functional mutations continue to emerge on the N-terminal domain (NTD) of the spike protein in SARS-CoV-2 Omicron subvariants. Understanding the immunogenicity of Omicron NTD and the properties of antibodies elicited by it is crucial for comprehending the impact of NTD mutations on viral fitness and guiding vaccine design. In this study, we find that most of NTD-targeting antibodies isolated from individuals with BA.5/BF.7 breakthrough infection (BTI) are ancestral (wildtype or WT)-reactive and non-neutralizing. Surprisingly, we identified five ultra-potent neutralizing antibodies (NAbs) that can only bind to Omicron but not WT NTD. Structural analysis revealed that they bind to a unique epitope on the N1/N2 loop of NTD and interact with the receptor-binding domain (RBD) via the light chain. These Omicron-specific NAbs achieve neutralization through ACE2 competition and blockage of ACE2-mediated S1 shedding. However, BA.2.86 and BA.2.87.1, which carry insertions or deletions on the N1/N2 loop, can evade these antibodies. Together, we provided a detailed map of the NTD-targeting antibody repertoire in the post-Omicron era, demonstrating their vulnerability to NTD mutations enabled by its evolutionary flexibility, despite their potent neutralization. These results highlighted the importance of considering the immunogenicity of NTD in vaccine design. Author SummaryCOVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major global public health concern four years after its emergence. The N-terminal domain (NTD) is a critical component of the spike glycoprotein, which is pivotal for SARS-CoV-2 cellular entry and serves as a primary target for antibody therapeutics and vaccine development. Characterizing the properties of antibodies elicited by NTD of Omicron sublineages is crucial for understanding viral evolution and guiding vaccine design. Here, we show that Omicron infection after vaccination induces majorly non-neutralizing NTD antibodies. Still, we identified a class of ultra-potent neutralizing antibodies (NAbs) which specifically bind to the NTD of Omicron sublineages. These NAbs neutralize the virus by competing with ACE2 and blocking ACE2-mediated S1 shedding. Structural analyses reveal that these antibodies target a unique epitope on the N1/N2 loop of NTD, and intriguingly interact with the receptor-binding domain (RBD) of spike glycoprotein. This class of NAbs with the special binding pattern, are escaped by BA.2.86 and BA.2.87.1 sublineages, shedding light on the role of recently emerged mutations in the N1/N2 loop of NTD. Our findings provide fresh insights into the immunogenicity of Omicron NTD, highlighting its capacity for antibody evasion due to its evolutionary flexibility. This underscores the importance of carefully considering the NTD component in vaccine design.

immunology↗

bioRxiv2024

Spatial gene expression at single-cell resolution from histology using deep learning with GHIST

The increased use of spatially resolved transcriptomics provides new biological insights into disease mechanisms. However, the high cost and complexity of these methods are barriers to broad clinical adoption. Consequently, methods have been created to predict spot-based gene expression from routinely-collected histology images. Recent benchmarking showed that current methodologies have limited accuracy and spatial resolution, constraining translational capacity. Here, we introduce GHIST, a deep learning-based framework that predicts spatial gene expression at single-cell resolution by leveraging subcellular spatial transcriptomics and synergistic relationships between multiple layers of biological information. We validated GHIST using public datasets and The Cancer Genome Atlas data, demonstrating its flexibility across different spatial resolutions and superior performance. Our results underscore the utility of in silico generation of single-cell spatial gene expression measurements and the capacity to enrich existing datasets with a spatially resolved omics modality, paving the way for scalable multi-omics analysis and new biomarker discoveries.

bioinformatics↗

bioRxiv2024

A Mechanistic Understanding of the Activity-Stability Trade-off in PETase

Enzymatic degradation of poly(ethylene terephthalate) (PET) has garnered considerable interest in plastic recycling efforts. Despite numerous descriptions of both natural and engineered enzymes, the fundamental mechanism underlying PETase-catalyzed PET depolymerization at the solid-liquid interface remains elusive. This lack of understanding hampers the rational design of highly efficient depolymerases. Here, we employ multiscale simulations and experiments to elucidate the complete catalytic pathway of IsPETase, from enzyme adsorption at the interface to PET fragment capture, conformational refinement, and ester bond cleavage. Both endo- and exo-cleavage modes of the enzyme are identified, indicating its capacity for endo- and exo-lytic activities. We discover that the trade-off between the activity and stability of IsPETases PET-capturing pliers brings compromises to its PET depolymerization performance. Reshaping the loop dynamics of the enzyme can break this trade-off and enhance its stability and activity simultaneously, as demonstrated by the evolved variant HotPETase. Overall, our study offers comprehensive details into how PETase functions at the interface and provides valuable insights for engineering efficient plastic-degrading enzymes.

biochemistry↗

bioRxiv2024

Multi-task benchmarking of spatially resolved gene expression simulation models

Computational methods for spatially resolved transcriptomics (SRT) are frequently developed and assessed through data simulation. The effectiveness of these evaluations relies on the simulation methods ability to accurately reflect experimental data. However, a systematic evaluation framework for spatial simulators is lacking. Here, we present SpatialSimBench, a comprehensive evaluation framework that assesses 13 simulation methods using 10 distinct STR datasets. We introduce simAdaptor, a tool that extends single-cell simulators to incorporate spatial variables, thus enabling them to simulate spatial data. SimAdaptor enables SpatialSimBench to be "back-wards" compatible. That is, it facilitates direct comparison between spatially aware simulators and existing non-spatial single-cell simulators through the adaption. Through SpatialSimBench, we demonstrate the feasibility of leveraging existing single-cell simulators for SRT data and highlight performance differences among methods. Additionally, we evaluate the simulation methods based on a total of 35 metrics across data property estimation, various downstream analysis and scalability. In total, we generated 4550 results from 13 simulation methods, 10 spatial datasets and 35 metrics. Our findings reveal that model estimation can be impacted by distribution assumptions and dataset characteristics. In summary, our evaluation and the evaluation framework will provide guidelines for selecting appropriate methods for specific scenarios and informing future method development.

bioinformatics↗

bioRxiv2024

Optimal CXCR5 Expression during Tfh Maturation Involves the Bhlhe40-Pou2af1 Axis

The pair of transcription factors Bcl6-Blimp1 is well-known for follicular T helper (Tfh) cell fate determination, however, the mechanism(s) for Bcl6-independent regulation of CXCR5 during Tfh migration into germinal center (GC) is still unclear. In this study, we uncovered another pair of transcription factors, Bhlhe40-Pou2af1, that regulates CXCR5 expression. Pou2af1 was specifically expressed in Tfh cells whereas Bhlhe40 expression was found high in non-Tfh cells. Pou2af1 promoted Tfh formation and migration into GC by upregulating CXCR5 but not Bcl6, while Bhlhe40 repressed this process by inhibiting Pou2af1 expression. RNA-Seq analysis of antigen-specific Tfh cells generated in vivo confirmed the role of Bhlhe40-Pou2af1 axis in regulating optimal CXCR5 expression. Thus, the regulation of CXCR5 expression and migration of Tfh cells into GC involves a transcriptional regulatory circuit consisting of Bhlhe40 and Pou2af1, which operates independent of the Bcl6-Blimp1 circuit that determines the Tfh cell fate.

immunology↗

bioRxiv2024

Omicron-specific naive B cell maturation alleviates immune imprinting induced by SARS-CoV-2 inactivated vaccine

SARS-CoV-2 ancestral strain-induced immune imprinting poses great challenges to vaccine updates. Studies showed that repeated Omicron exposures could override immune imprinting induced by inactivated vaccines but not mRNA vaccines, a disparity yet to be understood. Here, we analyzed the underlying mechanism of immune imprinting alleviation in inactivated vaccine (CoronaVac) cohorts. We observed in CoronaVac-vaccinated individuals who experienced BA.5/BF.7 breakthrough infection (BTI), the proportion of Omicron-specific memory B cells (MBCs) substantially increased after an extended period post-Omicron BTI, with their antibodies displaying enhanced somatic hypermutation and neutralizing potency. Consequently, the neutralizing antibody epitope distribution encoded by MBCs post-BA.5/BF.7 BTI after prolonged maturation closely mirrors that in BA.5/BF.7-infected unvaccinated individuals. Together, these results indicate the activation and expansion of Omicron-specific naive B cells generated by first-time Omicron exposure helped to alleviate CoronaVac-induced immune imprinting, and the absence of this process should have caused the persistent immune imprinting seen in mRNA vaccine recipients. HighlightsO_LILongitudinal MBC profiling of CoronaVac-vaccinated individuals following BA.5 BTI C_LIO_LIOmicron-specific MBC proportion rises greatly after extended period post-BA.5 BTI C_LIO_LIOmicron-specific naive B cell maturation reduces ancestral strain immune imprinting C_LI

immunology↗

bioRxiv2024

Coxsackievirus group B3 regulates ASS1-mediated metabolic reprogramming and promotes macrophage inflammatory polarization in viral myocarditis

Coxsackievirus group B3 (CVB3) belongs to the genus Enteroviruses of the family Picornaviridae and is the main pathogen underlying viral myocarditis (VMC). No specific therapeutic is available for this condition. Argininosuccinate synthase 1 (ASS1) is a key enzyme in the urea cycle that converts citrulline and aspartic acid to argininosuccinate. Here, we found that CVB3 and its capsid protein VP2 inhibit the autophagic degradation of ASS1 and that CVB3 consumes citrulline to upregulate ASS1, triggers urea cycle metabolic reprogramming, then activates macrophages to develop pro-inflammatory polarization, thereby promoting the occurrence and development of VMC. Conversely, citrulline supplementation to prevent depletion can downregulate ASS1, rescue macrophage polarization, and alleviate the pathogenicity of VMC. These findings provide a new perspective on the occurrence and development of VMC, revealing ASS1 as a potential new target for the treatment of this disease. IMPORTANCEViral myocarditis (VMC) is a common and potentially life-threatening myocardial inflammatory disease, most commonly caused by CVB3 infection. So far, the pathogenesis of VMC caused by CVB3 is mainly focused on two aspects: one is the direct myocardial injury caused by a large number of viral replication in the early stage of infection, and the other is the local immune cell infiltration and inflammatory damage of the myocardium in the adaptive immune response stage. There are few studies on the early innate immunity of CVB3 infection in myocardial tissue, but the appearance of macrophages in the early stage of CVB3 infection suggests that they can play a regulatory role as early innate immune response cells in myocardial tissue. Here, we discovered a possible new mechanism of VMC caused by CVB3, revealed new drug targets for anti-CVB3 and discovered the therapeutic potential of citrulline for VMC.

microbiology↗

bioRxiv2024

Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection

Clostridioides difficile infection (CDI) is one of the leading causes of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, its exact mechanisms of action and long-term safety are not fully understood. Defined consortia of clonal bacterial isolates, known as live biotherapeutic products (LBPs), have been proposed as an alternative therapeutic option. However, the rational design of LBPs remains challenging. Here, we employ a computational pipeline and three independent metagenomic datasets to systematically identify microbial strains that have the potential to inhibit CDI. We first constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) at the strain level. We then identified multiple potential protective nrMAGs that can be candidates for the design of microbial consortia targeting CDI, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these potential protective nrMAGs were found to play an important role in the success of FMT, and the majority of the top protective nrMAGs can be validated by various previously reported findings. Our results demonstrate a computational framework for the rational selection of microbial strains targeting CDI, paving the way for the computational design of microbial consortia against other enteric infections.

microbiology↗

bioRxiv2024

Rhizobial effector NopM ubiquitinates Nod factor receptor NFR5 and promotes rhizobial infection in Lotus japonicus

Bacterial pathogens and nitrogen-fixing rhizobia employ type III protein secretion system (T3SS) effectors as potent tools to manipulate plant signaling pathways, thereby facilitating infection and host colonization. However, the molecular mechanisms by which rhizobial effectors affect legume infection remain largely elusive. In this study, we investigated the symbiotic role of T3SS effectors in the interaction between Sinorhizobium fredii NGR234 and Lotus japonicus. Mutants deficient in the T3SS genes Tts1 or NopA showed enhanced rhizobial infection of L. japonicus roots. Further mutant analysis showed that the NopT effector negatively affects infection, while the NopM effector in the absence of NopT promotes infection. Notably, NopM interacts with the Nod factor receptors LjNFR1 and LjNFR5. NopM ubiquitinates LjNFR5 on ten lysine residues as identified using mass spectrometry. Expression of NopM in L. japonicus resulted in an approximately twofold increase in LjNFR5 protein levels and enhanced rhizobial infection. Our findings indicate that NopM directly interferes with the symbiotic signaling pathway through interaction and ubiquitination of Nod factor receptors, which likely benefits rhizobial infection of L. japonicus. Our research contributes to the intricate interplay between the Nod factor signaling pathway and rhizobial T3SS effectors delivered into host cells. Significance StatementThis study unravels intricate mechanisms underlying the symbiotic interaction between Sinorhizobium fredii NGR234 and Lotus japonicus. By focusing on the role of the rhizobial effector NopM, this research sheds light on how bacteria manipulate host symbiotic signaling to promote infection and colonization. NopM interacts with NFRs and ubiquitinates LjNFR5, suggesting a novel strategy employed by rhizobia to enhance symbiotic signaling.

microbiology↗

bioRxiv2024

Humoral immunogenicity comparison of XBB and JN.1 in human infections

The continuous evolution of SARS-CoV-2, particularly the emergence of the BA.2.86/JN.1 lineage replacing XBB lineages, necessitates re-evaluation of current vaccine compositions. Here, we provide a comprehensive analysis of the humoral immune response to XBB and JN.1 human exposures, emphasizing the need for JN.1-lineage-based boosters. We demonstrate the antigenic distinctiveness of XBB and JN.1 lineages in SARS-CoV-2-naive individuals but not in those with prior vaccinations or infections, and JN.1 infection elicits superior plasma neutralization titers against its subvariants. We highlight the strong immune evasion and receptor binding capability of KP.3, supporting its foreseeable prevalence. Extensive analysis of the BCR repertoire, isolating [~]2000 RBD-specific monoclonal antibodies (mAbs) with their targeting epitopes characterized by deep mutational scanning (DMS), underscores the systematic superiority of JN.1-elicited memory B cells (MBCs). Notably, Class 1 IGHV3-53/3-66-derived neutralizing antibodies (NAbs) contribute majorly within wildtype (WT)-reactive NAbs against JN.1. However, KP.2 and KP.3 evade a substantial subset of them, even those induced by JN.1, advocating for booster updates to KP.3 for optimized enrichment. JN.1-induced Omicron-specific antibodies also demonstrate high potency across all Omicron lineages. Escape hotspots of these NAbs have mainly been mutated in Omicron RBD, resulting in higher immune barrier to escape, considering the probable recovery of previously escaped NAbs. Additionally, the prevalence of broadly reactive IGHV3-53/3-66- encoding antibodies and MBCs, and their capability of competing with all Omicron-specific NAbs suggests their inhibitory role on the de novo activation of Omicron-specific naive B cells, potentially explaining the heavy immune imprinting in mRNA-vaccinated individuals. These findings delineate the evolving antibody response to Omicron antigenic shift from XBB to JN.1, and highlight the importance of developing JN.1 lineage, especially KP.3-based vaccine boosters, to enhance humoral immunity against current and future SARS-CoV-2 variants.

immunology↗