Biology subjects

Kassab, M.

Publications and source records attributed to Kassab, M..

4 recordsLinked to original sources

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

A hyperparameter benchmark of VAE-based methods for scRNA-seq batch integration

We present the first systematic benchmark of model-architecture hyperparameters for variational autoencoder (VAE) methods for single-cell RNA-seq batch integration within scvi-tools, comparing scVI, MrVI, and LDVAE across four heterogeneous datasets under two feature regimes (all genes vs highly variable genes (HVGs)). We investigated 960 trainings (120 configurations) varying latent size and network depth/width, and evaluated with a standardized scIB metric suite covering batch removal and biological conservation (Batch ASW, PCR-batch, iLISI, graph connectivity, NMI, ARI, label ASW, isolated-label F1/ASW, cLISI, trajectory conservation), plus qualitative UMAP/t-SNE and PCA, random projection, and unintegrated baselines. Results show dataset-dependent trade-offs: scVI performs best overall via stronger batch correction; LDVAE can better preserve biological structure in some datasets; MrVI is stable and excels at batch correction in multi-protocol settings but is more resource-intensive. HVG-only training generally outperforms full-gene training for all models. Hyperparameter analysis suggests moderate-to-high latent dimensionality (>30) often gives the best balance; sensitivity to latent size tracks dataset heterogeneity (tissues, labs, chemistries, gene coverage), with larger latents improving batch mixing but sometimes reducing biological conservation. We provide model- and dataset-specific guidelines for practical defaults and tuning of VAE-based integration in single-cell studies. Reproducibility code is available on GitHub at: https://github.com/Kassab11/A-hyperparameter-benchmark-of-VAE-based-methods-for-scRNA-seq-batch-integration

bioinformatics↗

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↗

bioRxiv2019

Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats

In the present study we developed an excitotoxic spinal cord injury (SCI) model using kainic acid (KA) to evaluate of the therapeutic potential of human olfactory bulb neural stem cells (h-OBNSCs) for spinal cord injury (SCI). In a previous study, we assessed the therapeutic potential of these cells for SCI; all transplanted animals showed successful engraftment. These cells differentiated predominantly as astrocytes, not motor neurons, so no improvement in motor functions was detected. In the current study we used estrogen as neuroprotective therapy before transplantation of OBNSCs to preserve some of endogenous neurons and enhance the differentiation of these cells towards neurons. The present work demonstrated that the h-GFP-OBNSCs were able to survive for more than eight weeks after sub-acute transplantation into injured spinal cord. Stereological quantification of OBNSCs showed approximately a 2.38-fold increase in the initial cell population transplanted. 40.91% of OBNSCs showed differentiation along the neuronal lineages, which was the predominant fate of these cells. 36.36% of the cells differentiated into mature astrocytes; meanwhile 22.73% of the cells differentiated into oligodendrocytes. Improvement in motor functions was also detected after cell transplantation.

neuroscience↗