# Mechanisms of T cell control in repeated HCV infection and innate immune responses that drive them

> **NIH NIH U19** · JOHNS HOPKINS UNIVERSITY · 2020 · $140,230

## Abstract

Project Summary 
The study of immune responses to HCV has provided important insight into protective immunity, 
but more research is needed to identify clear correlates of protective immunity for vaccine 
design. The overall goal of the proposed research project is to define the innate immune and T 
cell responses that allow protective immunity against the broadest array of infecting hepatitis C 
viruses by studying people who are repeatedly exposed to and control HCV. Longitudinal 
assessment of those who are repeatedly exposed with documented re-exposure to and control 
of multiple infections may represent the best opportunity to find correlates of truly protective 
immunity to mimic in vaccine development. A number of vaccine adjuvants activate innate 
immune sensing pathways that affect vaccine responses. Thus, we plan to assess the earliest 
innate response to HCV infection to identity those that play a key role in the priming, expansion, 
and polarization of effective adaptive immune responses and improve selection of a vaccine 
adjuvant that enhances induction of protective responses. We also plan to analyze T cell 
responses to HCV infection that result in control of HCV upon repeated exposure. 
Understanding protective T cell responses will enhance creation of a vaccine that induces T 
cells capable of clearing cells infected with any virus that evades the frontline neutralizing 
antibodies. We will analyze our T cell and cytokine data from this project in the context of 
antibody responses in the same subjects (Project 1- Ray) and with evaluation of the infecting 
HCV sequence (Project 3-Shaw). Combined data from this Project with Project 1 (Ray, humoral 
response to HCV) will allow us to determine how the innate response to HCV supports the 
generation of antibodies that effectively neutralize infection. Using sequence data from Project 3 
(Shaw) in combination with data on T cell responses from this Project and neutralizing antibody 
responses in Project 1 will allow us to determine how repeated exposure to close but not 
identical viral sequence affects adaptive immune responses. An assessment of viral sequence 
homology and the effects on the downstream adaptive immune response will provide 
information relevant to several viral infections where viral sequence varies, including HCV, with 
the goal of increasing the chances that vaccination promotes adaptive immune responses that 
prevent rather than promote disease. In sum, we anticipate that the proposed research studying 
the innate and adaptive T cell immune responses of people who are repeatedly exposed but 
don't develop persistent HCV infection will define correlates of protective immunity to target in 
vaccine design.

## Key facts

- **NIH application ID:** 9900738
- **Project number:** 5U19AI088791-10
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ANDREA L COX
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $140,230
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900738

## Citation

> US National Institutes of Health, RePORTER application 9900738, Mechanisms of T cell control in repeated HCV infection and innate immune responses that drive them (5U19AI088791-10). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9900738. Licensed CC0.

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