# Vaccine against HCV in nonhuman primates

> **NIH NIH U19** · STANFORD UNIVERSITY · 2023 · $122,522

## Abstract

ABSTRACT – CORE B (NONHUMAN PRIMATE CORE)
After over 3 decades since the discovery of Hepatitis C virus as one cause of hepatitis and cancer in patients, a 
preventive vaccine is still not available. More alarming is the fact that precise correlates of protection remain 
elusive. While passively administered neutralizing antibodies have been able to prevent initiation of infection in 
chimpanzees, the same treatment in the context of established infection just gave rise to mutants no longer 
susceptible to neutralization by this particular Mab and without apparent decrease in replication fitness. 
Conversely, spontaneous resolution of the infection as seen in about 25% of patient appears to primarily rely on 
cell mediated immune responses such as intra-hepatic CTLs. Generating such response via immunization has 
been a steep challenge given the multiple mechanism used by the virus to evade the effector antiviral responses. 
While recent development of antiviral agents have succeeded in the elimination of the majority of treated patients, 
this cure is expensive and patients having cleared infection therapeutically generally do not develop protective 
responses to a reinfection. To make matters worse, subclinical HCV infection not only does not generate 
protective response against superinfection but appears to paralyze many cell mediated effector immune 
functions, via the recruitment of regulatory T cells in the liver. 
Thus, generating potent and lasting protective mechanisms against HCV infection will require novel approaches, 
targeting both humoral and cell mediated antiviral responses, which is the goal of this collaborative program. 
The generation of broadly neutralizing antibodies will be attempted using HCV E1/E2 wild-type and optimized 
scaffolds that will minimize the presentation of non or subtype only neutralizing epitopes while presenting 
conserved epitopes across the 7 HCV genotypes along with potent adjuvants. A second approach will use a 
combination of live attenuated viral vector presenting non structural proteins Mosaic recombinant proteins in 
efforts to generate potent CTLs to HCV. This nonhuman primate Core will allow for testing each approach 
separately and in combination in a host that closely mimic the human immune system and repertoire, allowing 
for optimization of the responses and their analyses ex vivo for efficacy. This will be accomplished in a series of 
studies using the Indian origin macaque model of immunization, which will allow for repeated sampling and 
procurement of blood and bone marrow samples as well as biopsies of draining lymph nodes and liver of the 
entire monitoring period to Projects 2 and 3.

## Key facts

- **NIH application ID:** 10797239
- **Project number:** 5U19AI159840-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Francois J Villinger
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $122,522
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797239

## Citation

> US National Institutes of Health, RePORTER application 10797239, Vaccine against HCV in nonhuman primates (5U19AI159840-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10797239. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*