Biology subjects

Mishra, N.

Publications and source records attributed to Mishra, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Protective pan-betacoronavirus neutralizing antibodies by vaccination

The continued emergence of betacoronaviruses underscores the urgent need for vaccines that provide broadly protective immunity. Here, we present an epitope-focused vaccine strategy targeting the conserved S2 stem-helix region of the spike fusion machinery, a broadly neutralizing antibody-(bnAb) epitope shared across betacoronaviruses yet partially occluded on the native spike. Immunization of non-human primates with engineered S2 stem-helix nanoparticle immunogens, alone or followed by a SARS-CoV-2 BA.1 spike mRNA boost, elicited broadly cross-reactive antibody responses against sarbecoviruses, merbecoviruses, and embecoviruses and neutralized SARS-CoV-2, multiple variants, other sarbecoviruses, and MERS-CoV. Vaccine-elicited monoclonal antibodies displayed broad in-vitro neutralizing activity and protected against both SARS-CoV-2 and MERS-CoV in-vivo. Structural analyses revealed conserved features between rhesus and human stem-helix bnAbs, supporting the translational potential. Overall, our findings provide proof-of-concept that epitope-focused nanoparticle immunogens can target partially occluded, immunoquiescent bnAb epitopes, laying the groundwork for pan-betacoronavirus vaccines that provide broad protection and strengthen pandemic preparedness. ONE SENTENCE SUMMARYEpitope-focused S2 stem-helix nanoparticle immunogens elicit protective broadly neutralizing antibodies (bnAbs) against diverse betacoronaviruses in non-human primates, establishing a framework for development of pan-betacoronavirus vaccines.

immunology↗

bioRxiv2026

Early clonal dominance at priming sets the trajectory for broad HIV serum neutralization

Inducing broadly neutralizing antibodies (bnAbs) remains a central challenge in HIV vaccine development 1-3. Germline-targeting immunogens are designed to activate rare bnAb precursor B cell lineages 4-12, yet the relationships between priming efficiency, clonal dominance, and downstream serum neutralization remain poorly defined. We recently demonstrated that vaccination with an engineered V2-apex germline-targeting trimer Q23-APEX-GT2 successfully recruits and activates rare long-CDRH3 B cell precursors in outbred macaques 13. Here, we dissect the immunological mechanisms governing bnAb precursor priming and early B cell expansion and define clonal features that drive progression to serum neutralization breadth. Our antigen-specific B cell analyses showed that Q23-APEX-GT2 consistently engaged long-CDRH3 precursors, although priming efficiency varied across animals. Longitudinal deep lineage tracing across lymph node and blood compartments revealed that early recruitment of multiple diverse long-CDRH3 lineages, followed by preferential expansion and dominance of one or two clones, strongly predicted serum neutralization potency. Subsequent CAP256.SU SHIV infection efficiently recalled vaccine-seeded clones, accelerated affinity maturation, and drove broad heterologous neutralization in most animals. Notably, one macaque with diverse and expanded V2-apex lineages rapidly achieved [~]70% serum neutralization breadth. Importantly, longitudinal tracing revealed that bona fide bnAbs can emerge from vaccine-primed precursors, while also uncovering "born-wrong" bnAb-like lineages that expand yet remain non-neutralizing, despite structurally validated recognition of the V2-apex bnAb site. Together, these findings establish priming efficiency coupled with early clonal dominance as key determinants of serum bnAb induction and provide a mechanistic framework to guide rational HIV vaccine design.

immunology↗

bioRxiv2026

Heterologous betacoronavirus spike immunization in nonhuman primates elicits cross-reactive antibodies that neutralize both sarbeco- and merbecoviruses

In anticipation of future coronavirus (CoV) pandemics, developing vaccines that elicit broadly neutralizing antibodies (bnAbs) against diverse CoVs is critical. Here, we vaccinated rhesus macaques with SARS-CoV-2 spike (S)-protein, then boosted with heterologous {beta}-CoV S-proteins to focus responses to common conserved S2 bnAb epitopes. Initial SARS-CoV-2 priming elicited receptor-binding domain (RBD)-focused responses, while MERS-CoV boosting redirected responses toward the S2 region, including the stem-helix bnAb site. Although S2-directed serum cross-neutralization was undetectable and most isolated cross-reactive monoclonal antibodies (mAbs) targeted non-neutralizing epitopes, two S2 stem-helix mAbs were identified from memory B cells. These bnAbs neutralized diverse sarbeco- and merbecoviruses, including MERS-CoV, and conferred robust in vivo protection against SARS-CoV-2 challenge. Structural studies revealed that these macaque bnAbs closely mimic human S2-stem bnAbs induced by infection. These findings provide proof-of-principle for vaccination strategies that elicit broadly protective {beta}-coronavirus responses and highlight non-human primates as a translational model for evaluating S2-targeted immunogens.

immunology↗

bioRxiv2025

Structure-guided design of native-like HIV Env Single Chain Trimers for enhanced stability, immunogenicity, and versatile vaccine delivery

Stabilizing the HIV envelope (Env) trimer in its native prefusion conformation is key to eliciting broadly neutralizing antibodies (bnAbs). We present a generalizable single-chain trimer-(SCT) design platform that enables the production of stable, native-like Env trimers across diverse HIV strains. Using a structure-guided approach, we developed CAP256.SU-SCT9, based on a CAP256.SU Env shown to induce V2-apex bnAbs in humans and rhesus macaques. CAP256.SU-SCT9 trimer exhibited native-like structure, bnAb-specific antigenicity, authentic glycosylation, and compatibility with nucleic acid and nanoparticle delivery. We extended this design strategy to a panel of HIV Envs representing global diversity, and immunogens known to initiate bnAb responses in humans. Structural analyses confirmed that SCTs consistently maintained prefusion-closed conformations, favorable glycan profiles, strong binding to trimer-specific bnAbs, and low reactivity with non-neutralizing antibodies. These findings establish SCT as a versatile platform for HIV trimer immunogen design, with potential to support next-generation vaccines aimed at eliciting protective bnAb responses.

immunology↗

bioRxiv2025

Germline-targeting HIV immunogen induces cross-neutralizing antibodies in outbred macaques

Germline-targeting-(GT) is a promising strategy to activate rare broadly neutralizing antibody (bnAb)-producing B cells against HIV, but induction of such responses in outbred animals has not been achieved. Using antibody-guided structure-based design, we engineered a germline-targeting trimer immunogen Q23-APEX-GT2 that primes diverse V2-apex bnAb precursors. Q23-APEX-GT2 efficiently activated V2-apex-specific B cells in humanized knock-in mice and consistently elicited immunofocused antibody responses in rhesus macaques, priming multiple long CDRH3-loop bnAb-B cell lineages. Monoclonal antibodies from immunized macaques exhibited broad heterologous HIV trimer binding and cross-neutralization. Atomic-level structural studies confirmed precise epitope targeting and revealed CDRH3-paratope configurations that mirrored those of human V2-apex bnAbs. This study provides proof-of-principle for successful priming and maturation of authentic V2-apex bnAb precursors in outbred macaques, underscoring the potential of V2-apex-targeted vaccines. HIGHLIGHTSO_LIEngineered Q23-APEX-GT2 trimer to stimulate diverse V2-apex bnAb B cell precursors C_LIO_LIQ23-APEX-GT2 primed rare V2-apex bnAb B cells in mice and outbred rhesus macaques C_LIO_LIQ23-APEX-GT2 elicited immunofocused antibody responses and diverse V2-apex B cell lineages with desirable long-CDRH3 paratope properties C_LIO_LIQ23-APEX-GT2 alone induced V2-apex antibodies with broad HIV trimer binding and modest neutralization breadth C_LIO_LIStructural analysis confirmed bnAb site targeting, mirroring human and rhesus V2-apex bnAbs C_LI

immunology↗

bioRxiv2025

Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition

Protein-energy malnutrition (PEM) is a global health burden with lasting effects that extend well beyond the initial nutrient deficiency. To systematically investigate the long-term effects of a single episode of PEM on the structure and function of the intestinal epithelium and its associated microbiota, we employed a comprehensive multi-omics approach, including (spatial) transcriptomics, DNA methylation analysis, fecal metagenomics, and metabolomics. Our findings show that PEM persistently alters the intestinal epithelium by depleting Paneth cells and suppressing antimicrobial gene expression - changes linked to DNA methylation that persist despite dietary recovery. In germ-free mice, the sustained epithelial phenotype after was absent. We identified the microbial lipid metabolite 9-HODE and epigenetically deregulated PPAR-driven GDF15 expression as key molecular drivers of the persistent PEM-induced Paneth cell dysfunction. Targeting microbial lipid production and its link to the host GDF15 pathway could offer novel therapeutic strategies for long-term consequences of malnutrition and other Paneth cell-associated diseases.

immunology↗

bioRxiv2025

GhostFold: Accurate protein structure prediction using structure-constrained synthetic coevolutionary signals

The accuracy of protein structure prediction models such as AlphaFold2 is tightly coupled to the depth and quality of multiple sequence alignments (MSAs), posing a persistent challenge for proteins with few or no identifiable homologs. We present GhostFold, a method for conjuring structure-constrained synthetic MSAs from a single amino acid sequence, bypassing the need for traditional homology searches. Leveraging the ProstT5 protein language model and the 3Di structural alphabet, GhostFold projects a query sequence into a tokenized structural representation and iteratively back-translates to generate an ensemble of diverse, fold-consistent sequences. These synthetic alignments (pseudoMSAs) encode emergent coevolutionary constraints that are sufficient for high-accuracy structure prediction of difficult targets such as orphan proteins and hypervariable antibody loops. GhostFold consistently matches or exceeds the performance of MSA-based and language model-based structure predictors while being computationally lightweight and independent of large sequence databases. Notably, we observe a decoupling of confidence metrics (e.g., pLDDT) from prediction accuracy when using pseudoMSAs, suggesting that AlphaFold2s internal confidence calibration is strongly influenced by the statistical properties of natural sequence alignments. These results establish that structure-guided synthetic MSAs can functionally substitute for evolutionary data, offering a scalable and generalizable solution to one of the central limitations in computational structural biology. GhostFold represents a shift from passive data mining to intelligent sequence synthesis, redefining how structural priors are encoded in deep learning-based protein folding.

bioinformatics↗

bioRxiv2025

Urinary Exosomal miRNA Profiling Reveals Sensitive Non-Invasive Diagnosis of Bladder Cancer

UnstructuredmiRNAs represent a transformative advancement in both research and clinical management of urinary bladder cancer (UBC), emerging as clinically significant molecular targets with the potential to revolutionize existing diagnostic standards. This study exploited the robust stability of miRNAs and profiled urinary miRNAs in UBC patients and controls through miRNA sequencing, revealing an expanded and altered miRNA repertoire in cancer samples. Validation in an independent cohort revealed fold changes for miR-6724-5p, miR-1273h-5p, miR-7704, miR-200-5p, and miR-10400-5p ranged from [~]46 to [~]2,777 (p < 0.01). Stage-specific analyses highlighted dynamic miRNA expression linked to tumor progression. Diagnostic evaluation identified an optimal three-miRNA panel comprising miR-6724-5p, miR-10400-5p, and miR-7704, achieving diagnostic accuracies (AUC > 70%) and high sensitivity (>90%). These data demonstrate the potential of urinary mature miRNAs as robust biomarkers for non-invasive detection and monitoring of UBC in early stages, supporting their translation into clinical diagnostic assays pending larger prospective studies. StructuredO_ST_ABSBackgroundC_ST_ABSUrinary microRNAs (miRNAs) are promising candidates due to their molecular stability and disease-specific expression. miRNAs represent a transformative advancement in both research and clinical management of urinary bladder cancer (UBC), emerging as actionable molecular targets with the potential to revolutionize existing diagnostic standards. MethodsSmall RNA sequencing was performed on urine samples from UBC patients and healthy controls to profile miRNA expression. Mature miRNAs were prioritized by exclusion of precursor forms using computational filtering. Validation by quantitative RT-PCR was conducted on an independent, age-matched cohort (n = 45). Diagnostic potential of candidate miRNAs was assessed by receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses. ResultsSequencing identified 865 known and 11 novel miRNAs, with UBC samples showing greater miRNA diversity (708 known miRNAs) compared to controls (540). Ten miRNAs were significantly dysregulated in UBC (p < 0.05). Validation revealed fold changes for miR-6724-5p, miR-1273h-5p, miR-7704, miR-200-5p, and miR-10400-5p ranged from [~]46 to [~]2,777 (p < 0.01). Stage-specific analyses highlighted dynamic miRNA expression linked to tumor progression. A three-miRNA panel (miR-6724-5p, miR-10400-5p, miR-7704) demonstrated superior diagnostic performance (AUC > 70%, sensitivity > 90%). ConclusionMature urinary miRNAs exhibit reproducible, stage-specific dysregulation in UBC and a combinatorial panel offers sensitive, specific non-invasive detection. These findings warrant further multicenter validation for clinical application.

cancer biology↗

bioRxiv2025

Consistent Induction of Broadly Neutralizing HIV Antibodies by a Novel Two-Step Mechanism Informs Immunogen Design

A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a novel two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.

immunology↗

bioRxiv2025

Rapid acquisition of HIV-1 neutralization breadth in a rhesus V2 apex germline antibody mouse model after a single bolus immunization

Current vaccine strategies to elicit broadly neutralizing antibodies (bnAbs) against HIV-1 generally propose complex, multi-boost immunization regimens. In rhesus macaques, SHIV infection has been observed to rapidly drive the development of some classes of bnAbs that share structural similarities with those in humans. Here, we generated a knockin mouse model with B cells bearing the unmutated common ancestor (UCA) of the V2 apex-targeted bnAb lineage, V033-a. A single immunization of mice with a germline-targeting native-like trimer was sufficient to recapitulate the ontogeny of the mature rhesus bnAb in knockin mice--including rare, disfavored somatic mutations--leading to the induction of antibodies that exhibited potent neutralization against both autologous and heterologous tier 2 viruses. A boost with Env escape mutant trimers further improved breadth and potency, and cryo-EM structure revealed the structural basis for heterologous neutralization breadth. Non-human primate and mouse models can thus combine with structure to serve as a platform for identifying and confirming immunogens that streamline HIV-vaccination regimens.

immunology↗

bioRxiv2025

Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo

Early embryo geometry is one of the most invariant species-specific traits, yet its role in ensuring developmental reproducibility and robustness remains underexplored. Here, we show that in zebrafish, the geometry of the fertilized egg - specifically its curvature and volume - serves as a critical initial condition triggering a cascade of events that exert a lasting influence on development. Specifically, it guides asymmetric cell divisions in the blastoderm, generating radial gradients of cell volume and nucleocytoplasmic ratio. These gradients generate mitotic phase waves, with individual cell cycle periods determined largely cell-autonomously by the nucleocytoplasmic ratio. Modeling and perturbation experiments demonstrate that reducing cell autonomy reshapes these waves, emphasizing the instructive role of geometry-derived volume patterns in setting the intrinsic period of the cell cycle oscillator. Remarkably, in addition to organizing cell cycles, early embryo geometry also spatially patterns zygotic genome activation (ZGA) at the midblastula transition, a key step in establishing embryonic autonomy. Disrupting geometry alters the ZGA pattern and causes ectopic germ layer specification, underscoring its developmental significance. Together, our findings reveal a novel symmetry-breaking function of early embryo geometry in coordinating cell cycle and transcriptional patterning, establishing a blueprint for robust embryogenesis.

developmental biology↗

bioRxiv2024

Bovine Formative Embryonic Stem Cell Plasticity in Embryonic and Extraembryonic Differentiation

Bovine embryonic stem cells (bESCs) can greatly enhance understanding of bovine embryonic development and applications for disease-resistance, biomedical and zoonotic pre-clinical models. However, formative bESCs with distinct morphology and complete differentiation capacity are still unreported. We document here the generation of bESCs which are pluripotent both in vitro and in vivo, and efficiently converted into neural progenitor cells (NPCs) and primordial germ cell-like cells (PGCLCs) by direct differentiation. These cells exhibited distinct metabolic features from human and mouse ESCs and early embryos. Formative bESCs contributed to a wide range of cell types within embryonic and extraembryonic tissues after aggregating with mouse and bovine embryos. The establishment of bovine formative ESCs with dual developmental plasticity represents a milestone for agricultural biotechnology and decoding the underlying mechanism of bona fide bovine pluripotency. Summary statementGenerating bovine ESCs would greatly enhance understanding of bovine embryonic development and bioengineering of cattle for disease-resistance, biomedical and zoonotic pre-clinical models.

developmental biology↗

bioRxiv2024

Conformational ensemble-based framework enables rapid development of Lassa virus vaccine candidates

Lassa virus (LASV), an arenavirus endemic to West Africa, poses a significant public health threat due to its high pathogenicity and expanding geographic risk zone. LASV glycoprotein complex (GPC) is the only known target of neutralizing antibodies, but its inherent metastability and conformational flexibility have hindered the development of GPC-based vaccines. We employed a variant of AlphaFold2 (AF2), called subsampled AF2, to generate diverse structures of LASV GPC that capture an array of potential conformational states using MSA subsampling and dropout layers. Conformational ensembles identified several metamorphic domains--areas of significant conformational flexibility--that could be targeted to stabilize the GPC in its immunogenic prefusion state. ProteinMPNN was then used to redesign GPC sequences to minimize the mobility of metamorphic domains. These redesigned sequences were further filtered using subsampled AF2, leading to the identification of promising GPC variants for further testing. A small library of redesigned GPC sequences was experimentally validated and showed significantly increased protein yields compared to controls. Antigenic profiles indicated these variants preserved essential epitopes for effective immune response, suggesting their potential for broad protective efficacy. Our results demonstrate that AI-driven approaches can predict the conformational landscape of complex pathogens. This knowledge can be used to stabilize viral proteins, such as LASV GPC, in their prefusion conformation, optimizing them for stability and expression, and offering a streamlined framework for vaccine design. Our deep learning / machine learning enabled framework contributes to global efforts to combat LASV and has broader implications for vaccine design and pandemic preparedness.

immunology↗

bioRxiv2024

Decoding protein dynamicity in DNA ligase activity through deep learning-based structural ensembles

Numerous proteins perform their functions by transitioning between various structures. Understanding the conformational ensembles associated with these states is essential for uncovering crucial mechanistic aspects that regulate protein function. In this study, we utilized AlphaFold3 (AF3) to investigate the structural dynamics and mechanisms of enzymes involved in DNA homeostasis, using NAD-dependent Taq ligases and human DNA Ligase 1 as a case example. Modifying the input parameters for AF3 yielded detailed conformational states of a DNA-binding enzyme, thereby offering enhanced mechanistic insights. We applied AF3 to model the various stages of thermophilic Taq DNA ligase activity, from its ground state to substrate-bound complexes, revealing significant mobility in the N-terminal adenylation and C-terminal BRCT domains. These detailed structural ensembles provided novel insights into the enzymes behavior during DNA repair, underscoring the potential of AF3 in elucidating mechanistic details critical for therapeutic and biotechnological targeting. Extending this approach to human LIG1, we examined its end-joining activity on double-strand breaks (DSBs) with short 3 and 5 overhangs. In alignment with published experimental data, AF3 conformational ensembles indicated LIG1 has lower catalytic efficiency for 5 overhangs due to suboptimal DNA positioning within the catalytic site, demonstrating AF3s capability to capture subtle yet functionally significant conformational differences by generating conformational ensembles capturing greater structural variance.

molecular biology↗

bioRxiv2024

FUS controls muscle differentiation and structure through LLPS mediated recruitment of MEF2 and ETV5

FUS is an RNA binding protein mutated in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive muscle weakness. We show that ALS-associated FUS mutations lead to ultrastructural defects in muscle of FUS-ALS patients, with disruption of sarcomeres and mitochondria. Studies in mouse and Drosophila models demonstrate an evolutionary-conserved cell autonomous function of FUS in muscle development. Mechanistically, FUS is required for transcription of MEF2 dependent genes, binds to the promoter of genes bound by ETS transcription factors in particular ETV5 and co-activates transcription of MEF2 dependent genes with ETV5. FUS phase separates with ETV5 and MEF2A, and MEF2A binding to FUS is potentiated by ETV5. Last, Etv5 haploinsufficiency exacerbates muscle weakness in a mouse model of FUS-ALS. These findings establish FUS as an essential protein for skeletal muscle structure through its phase separation-dependent recruitment of ETV5 and MEF2, defining a novel pathway compromised in FUS-ALS.

neuroscience↗

bioRxiv2024

Non-random segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in daughter cells

The non-random segregation of organelles has been proposed to be an intrinsic mechanism that contributes to cell fate divergence during asymmetric cell division; however, in vivo evidence is sparse. Using super-resolution microscopy, we analysed the segregation of organelles during the division of the neuroblast QL.p in C. elegans larvae. QL.p divides to generate a daughter that survives, QL.pa, and a daughter that dies, QL.pp. We found that mitochondria segregate unequally by density and morphology and that this is dependent on mitochondrial fission and fusion. Furthermore, we found that mitochondrial density in QL.pp correlates with the time it takes QL.pp to die. We propose that low mitochondrial density in QL.pp promotes the cell death fate and ensures that QL.pp dies in a highly reproducible and timely manner. Our results provide the first in vivo evidence that the non-random segregation of mitochondria can contribute to cell fate divergence during asymmetric cell division.

developmental biology↗

bioRxiv2024

Computation-aided Design of Rod-Shaped Janus Base Nanopieces for Improved Tissue Penetration and Therapeutics Delivery

Despite the development of various drug delivery technologies, there remains a significant need for vehicles that can improve targeting and biodistribution in "hard-to-penetrate" tissues. Some solid tumors, for example, are particularly challenging to penetrate due to their dense extracellular matrix (ECM). In this study, we have formulated a new family of rod-shaped delivery vehicles named Janus base nanopieces (Rod JBNps), which are more slender than conventional spherical nanoparticles, such as lipid nanoparticles (LNPs). These JBNp nanorods are formed by bundles of DNA-inspired Janus base nanotubes (JBNts) with intercalated delivery cargoes. To develop this novel family of delivery vehicles, we employed a computation-aided design (CAD) methodology that includes molecular dynamics and response surface methodology. This approach precisely and efficiently guides experimental designs. Using an ovarian cancer model, we demonstrated that JBNps markedly improve penetration into the dense ECM of solid tumors, leading to better treatment outcomes compared to FDA-approved spherical LNP delivery. This study not only successfully developed a rod-shaped delivery vehicle for improved tissue penetration but also established a CAD methodology to effectively guide material design.

bioengineering↗

bioRxiv2023

Germline-targeting chimpanzee SIV Envelopes induce V2-apex broadly neutralizing-like B cell precursors in a rhesus macaque infection model

Eliciting broadly neutralizing antibodies-(bnAbs) remains a major goal of HIV-1 vaccine research. Previously, we showed that a soluble chimpanzee SIV Envelope-(Env) trimer, MT145K, bound several human V2-apex bnAb-precursors and stimulated an appropriate response in V2-apex bnAb precursor-expressing knock-in mice. Here, we tested the immunogenicity of three MT145 variants (MT145, MT145K, MT145K.dV5) expressed as chimeric simian-chimpanzee-immunodeficiency-viruses-(SCIVs) in rhesus macaques-(RMs). All three viruses established productive infections with high setpoint vRNA titers. RMs infected with the germline-targeting SCIV_MT145K and SCIV_MT145K.dV5 exhibited larger and more clonally expanded B cell lineages featuring long anionic heavy chain complementary-determining-regions-(HCDR3s) compared with wildtype SCIV_MT145. Moreover, antigen-specific B cell analysis revealed enrichment for long-CDHR3-bearing antibodies in SCIV_MT145K.dV5 infected animals with paratope features resembling prototypic V2-apex bnAbs and their precursors. Although none of the animals developed bnAbs, these results show that germline-targeting SCIVs can activate and preferentially expand B cells expressing V2-apex bnAb-like precursors, the first step in bnAb elicitation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC="FIGDIR/small/558743v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@17673c8org.highwire.dtl.DTLVardef@1ab61a8org.highwire.dtl.DTLVardef@98781forg.highwire.dtl.DTLVardef@1f63e9b_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗