# Mechanisms driving breadth of HCV neutralization during repeated control of acute infection in humans

> **NIH NIH U19** · JOHNS HOPKINS UNIVERSITY · 2020 · $175,232

## Abstract

Project 1: Mechanisms driving breadth of HCV neutralization during repeated control of acute infection 
in humans 
PI: Stuart C. Ray, M.D. 
The primary objective of Project 1 is to study mechanisms driving increased breadth of neutralizing antibody 
responses during repeated HCV infections that are successfully cleared. We have recently demonstrated that 
anti-HCV humoral immune responses drive the evolution of HCV proteins E1 and E2 during acute and chronic 
infection, indicating that neutralizing antibodies detected in our in vitro assays reduce viral fitness in vivo. We 
have also demonstrated that neutralizing antibodies form clusters of similar specificities by testing them 
against natural HCV variants that we have cloned in a functional library. We hypothesize that repeated 
stimulation with varying HCV envelope sequences during reinfection drives broadening of the neutralizing 
antibody response. Thus, we propose the following aims to elucidate the mechanisms driving HCV 
neutralization breadth during acute reinfection: (I) to examine dynamic changes in anti-HCV binding and 
neutralizing activity during HCV re-infection, (II) to determine the mechanistic basis for changes in neutralizing 
activity by characterizing the circulating B cell repertoire, and (III) to identify key HCV envelope sequence 
changes that drive broadening of neutralization during reinfection. We anticipate that accomplishing these 
aims in collaboration with Dr. Cox (project 2) and Dr.Shaw (Project 3) will reveal patterns of antigenic exposure 
that drive shifts in the B cell response, in a manner that will help guide vaccine design and increase 
understanding of the host-pathogen interaction.

## Key facts

- **NIH application ID:** 9900737
- **Project number:** 5U19AI088791-10
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** STUART C RAY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,232
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900737

## Citation

> US National Institutes of Health, RePORTER application 9900737, Mechanisms driving breadth of HCV neutralization during repeated control of acute infection in humans (5U19AI088791-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900737. Licensed CC0.

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