# Correlates of protective immunity to HCV and rational vaccine design: Project 3

> **NIH NIH U19** · EMORY UNIVERSITY · 2023 · $957,184

## Abstract

Hepatitis C virus (HCV) continues to infect ~71 million people worldwide with an estimated 1.5 to 2 million new
infections each year. A complete eradication of HCV infection warrants development of an effective vaccine that
can rapidly induce a durable anti-viral immunity and prevent infection. Evidence from spontaneous controllers
suggests that a broad and durable HCV-specific CD4 and CD8 T cell responses are critical for effective control
of HCV infection. In addition, a protective role for neutralizing antibody against viral glycoproteins E1&E2 has
also been implicated. Furthermore, it is critical generate anti-viral immunity in the liver (the primary site of virus
replication). Thus, the primary goal of this proposal is to develop a vaccination strategy using DNA, modified
vaccinia Ankara (MVA), and protein-based vaccines that will generate a robust and broad HCV specific T and B
cell responses in blood and liver against multiple HCV proteins. We hypothesize that induction of a strong, broad,
and persistent T cell response against HCV antigens in the blood and liver combined with induction of strong
neutralizing antibody response will provide protection against HCV infection and different combinations of
DNA/MVA/protein vaccination can be harnessed to achieve the desired protective immunity. We propose to
achieve these objectives using 3 specific aims. In Aim 1 we will construct and characterize DNA and MVA
vaccines expressing HCV core, NS3-NS5 and E1E2 proteins. In Aim 2 we will optimize the DNA/MVA vaccine
modality for inducing strong T cell and antibody responses. The optimizations will include testing the E1E2 in
two forms either presented on the virus-like particle (VLP) or secreted. In addition, we will test the influence of
CD40L adjuvant on cellular and humoral immunity. In Aim 3 we will optimize E1E2 protein boosts for DNA/MVA
vaccine for further enhancing the antibody responses. By completion of these studies we hope generate an
optimal vaccine against HCV that induces strong T cell and neutralizing antibody responses.

## Key facts

- **NIH application ID:** 10608113
- **Project number:** 5U19AI159819-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rama Rao Amara
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $957,184
- **Award type:** 5
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10608113

## Citation

> US National Institutes of Health, RePORTER application 10608113, Correlates of protective immunity to HCV and rational vaccine design: Project 3 (5U19AI159819-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10608113. Licensed CC0.

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