DeKosky Pilot Project Summary

This project will establish a new experimental pipeline for rapid analysis of antibody immune pressure against viral pathogens, which holds the potential to accelerate the discovery of therapeutic and vaccine candidates against persistent viruses. This project will develop new research tools to investigate adaptive immune pressure against human cytomegalovirus (HCMV), which is a highly prevalent pathogen infecting the majority of individuals in the world and causes significant morbidity and mortality in immunocompromised patients and in congenital infections with prevalence of around one in 200 births. Here we will develop a new antibody isolation assay to identify and express anti-HCMV glycoprotein B (gB) antibodies that have potential HCMV neutralization capacity among human antibody repertoires. We will also transfer established HCMV neutralization assays into a new high-throughput robotic format to rapidly screen our isolated antibodies for HCMV neutralization. This work will leverage established high-throughput immune profiling techniques recently invented by the PI to interrogate anti-HCMV antibody-based immunity and will greatly extend our capabilities in high-throughput sequencing and analysis of antiviral antibody repertoires. This pilot project will establish the protocols, research environment, and expertise to attract external funding and begin clinical research studies regarding the features of effective and ineffective adaptive immune pressure against HCMV infections. In particular, this project will establish a new research environment for follow-up collaborative studies investigating effective vs. ineffective adaptive immune pressure against HCMV in a prospective cohort of matched mother and infant pairs. In the long-term, the research catalyzed by this pilot project will accelerate growth of technologies for rapid analysis of adaptive immunity against persistent viruses. These new technologies will enable discovery of potent antibodies to prevent and treat viral infections in vulnerable populations, beginning with HCMV.