Biology subjects

Weglarz, M.

Publications and source records attributed to Weglarz, M..

4 recordsLinked to original sources

bioRxiv2026

A human-derived two-antibody cocktail confers prophylactic and therapeutic protection against authentic Mpox virus.

With sustained human-to-human transmission worldwide, Mpox virus remains a significant global health burden. However, there are no licensed therapeutics against Mpox, with clinical management limited to supportive care and pain management. Given the virus complex life cycles, effective treatments require the inhibition of both mature intracellular virions (MV) and extracellular virions (EV). Here, we describe the isolation of human monoclonal antibodies (mAbs) from antigen specific memory B cell using flow cytometry-based cell sorting. We also characterize the therapeutic potential of 2-mAb cocktails targeting both MV and EV using an in vitro neutralization assay and a mouse challenge model. Several developed human 2-mAb cocktails neutralized authentic Mpox in vitro. When administered 24 hours before or after Mpox challenge, the lead 2-mAb cocktail inhibited viral loads in mouse tissues, with the exception of the testes. Overall, our study identifies several human 2-mAb cocktails with therapeutic potential for controlling Mpox disease.

microbiology↗

bioRxiv2025

Antigen avidity drives the durability of the vaccine immune response.

One challenge in vaccine development is designing immunogens that elicit durable immunity. We hypothesized that antigen avidity regulates the magnitude, diversity, and durability of the vaccine immune response. We tested this in multiple preclinical HIV vaccine models using a neoteric mosaic nanoparticle platform. This allowed us to precisely modulate antigen avidity by varying multivalency and affinity independently, whilst keeping other variables constant. Antigen avidity drove seeding, interclonal competition, and immunodominance within germinal centers. High-valency immunogens promoted durable germinal center, memory B cell, serum antibody, and long-lived plasma cell responses. Restricting interclonal competition rescued B cell responses to low-valency immunogens. B cell receptor sequencing revealed that antigen valency had minimal impact on individual somatic hypermutations but promoted clonal diversity. Affinity worked in concert with valency in driving productive B cell responses, with multivalency having dominant influences. The results underscore the importance of antigen avidity in driving durable and diverse vaccine responses.

immunology↗

bioRxiv2023

A mutant fitness compendium in Bifidobacteria reveals molecular determinants of colonization and host-microbe interactions

Bifidobacteria commonly represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest as a probiotic therapy, predicting the nutritional requirements and health-promoting effects of Bifidobacteria is challenging due to major knowledge gaps. To overcome these deficiencies, we used large-scale genetics to create a compendium of mutant fitness in Bifidobacterium breve (Bb). We generated a high density, randomly barcoded transposon insertion pool in Bb, and used this pool to determine Bb fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. To enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1462 genes. We leveraged these tools to improve models of metabolic pathways, reveal unexpected host- and diet-specific requirements for colonization, and connect the production of immunomodulatory molecules to growth benefits. These resources will greatly reduce the barrier to future investigations of this important beneficial microbe.

microbiology↗

bioRxiv2021

Construction and characterization of a genome-scale ordered mutant collection of Bacteroides thetaiotaomicron

Genomic analyses have revealed how the gut microbiota impacts human health. However, knowledge about the physiology of most gut commensals is largely lacking. Here, we sorted cells from a pooled library to construct an ordered collection of transposon-insertion mutants in the model commensal Bacteroides thetaiotaomicron. We applied a pooling strategy with barcode sequencing to locate mutants and created a condensed collection with single insertions in 2,565 genes. This effort enabled the development of an accurate model for progenitor-collection assembly, which identified strain-abundance biases and multi-insertion strains as important factors that limit coverage. To demonstrate the potential for phenotypic screening, we analyzed growth dynamics and morphology of the condensed collection and identified growth defects and altered cell shape in the sphingolipid-synthesis gene BT0870 and the thiamine scavenging gene BT2397. Analyses of this collection and utilization of the platform described herein to construct future ordered libraries will increase understanding of gut commensal physiology and colonization strategies.

microbiology↗