Biology subjects

Galvez, N. M. S.

Publications and source records attributed to Galvez, N. M. S..

3 recordsLinked to original sources

bioRxiv2025

High-Throughput Antibody Neutralization Screening in Massively Parallel Droplet Arrays

Neutralizing antibodies provide rapid immune defense against infectious diseases, but are difficult to discover at scale because neutralization assays require live reporter cells and soluble monoclonal antibodies. Here we report Droplet Reporter Cell Testing for Neutralization (DrReCT-Neutralization) to screen antibody gene libraries for their ability to neutralize viral infections. We established the necessary engineered cell lines and validated the DrReCT screening platform using synthetic oligoclonal libraries, followed by an example discovery campaign that demonstrated scalable functional antibody data collection against viral diseases.

immunology↗

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↗