A vaccine design to induce protective B and T cell immunity against hepatitis C virus

Ended Cooperative Agreement Awarded Last action

Award ID
U19AI159840
Recipient
Awarding agency
Obligated
$36,130,494

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date
Originally
Funding
  • $31,255,003.00 Federal
  • $4,875,491.00 Non-federal
Place of performance
Palo Alto, CA 94304, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Overall component the overall goal of this U19 project is the development of an HCV vaccine to prevent disease progression after virus exposure in a vaccinated host. Our overall approach is based on a growing body of data from studies in patients undergoing primary HCV infections indicating that a subset of these individuals generates immune responses that result in viral clearance and conferring immunity against reinfection. This naturally occurring protective immunity appears to include early and robust humoral and cellular responses during the acute phase of infection. Consequently, the early kinetics, strength, and quality (i.e., cross-protective capacity of both humoral and cellular responses against the diversity of the evolving HCV quasispecies) are critical for efficient clearance of repeated exposures to diverse HCV isolates/infections in at-risk individuals. Thus, a successful vaccine will need to induce robust and durable adaptive B and T cell immune responses in the vaccinated host. This program is designed to achieve this goal by four complementary projects and a scientific core. Project 1 focuses on a structure-guided approach to develop an immunogen that enhances the induction of broadly neutralizing antibodies (BNABS) including those when combined lead to synergistic virus neutralization. This project will interact extensively with project 4 on structural analysis of HCV envelop glycoproteins and on structural aspects of BNABS and receptor binding to HCV particles. Project 2 will design HCV NS mosaic antigens for T cell recognition of HCV genotypes and subtypes that cause most infections globally. Mosaic antigens are designed computationally by recombination of viral genomic sequences retrieved from databases. Project 3 takes a systems approach to evaluate short- and long-term B and T cell responses and innate responses to vaccination with vaccines that are formulated in projects 1 and 3, and in combination with powerful adjuvants. These studies will be undertaken in non-human primates that will be executed in a scientific core. The administrative core will provide the operational support necessary to successfully achieved the goals we have laid out for each project and program as a whole. Taken together, the work proposed in these projects and scientific core are highly interdependent that will lead to a vaccine design capable to elicit protective B and T cell immunity against HCV. We expect that at the end of this program project, we will have a candidate vaccine to begin pre-clinical studies that will progress to phase I/II clinical trial.

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Subawards

Subrecipient Amount Awarded
Research Institute At Nationwide Children's Hospital The overall objective of the Project 2 workscope is to deliver a tetravalent T cell vaccine component that provides broad coverage of major global HCV genotypes… $68,864
University Of Louisiana At Lafayette Dr. Francois Villinger, Director of the University of Louisiana at Lafayette New Iberia Research Center, will be leading the nonhuman primate Core for the… $281,977
University Of Louisiana At Lafayette $173,562
The Governors Of The University Of Alberta The Houghton lab will express, purify and analyse various mtE1E2s in CHO cells and compare their properties with their current wtE1E2. The mtE1E2 designs will… $178,188
University Of Louisiana At Lafayette Dr. Francois Villinger, Director of the University of Louisiana at Lafayette New Iberia Research Center, will be leading the nonhuman primate Core for the… $36,706
Emory University The objective of the stated work is to conduct sequencing and bioinformatics analyses on B cells samples from NHP provided from Stanford to Emory. The data… $100,000
Purdue University "Dr. Kuhn will carry out structural studies of hepatitis C virus (HCV) glycoproteins E1E2 and the virus particle. In addition, the binding of neutralizing… $292,488
Research Institute At Nationwide Children's Hospital The overall objective of the Project 2 workscope is to deliver a tetravalent T cell vaccine component that provides broad coverage of major global HCV genotypes… $183,703
Fred Hutchinson Cancer Center Project 2 will provide a vaccine component that elicits T cell-mediated immunity against the most dominant global HCV genotypes. This T cell component will be… $32,328
Research Institute At Nationwide Children's Hospital The overall objective of the Project 2 workscope is to deliver a tetravalent T cell vaccine component that provides broad coverage of major global HCV genotypes… $248,142
Memorial University Of Newfoundland "John Law, PhD, a molecular virologist has guided the biochemical/physical interrogations of mutant E1E2s as purified proteins, the intracellular expressions of… $50,000
The Governors Of The University Of Alberta The Houghton lab will express, purify and analyse various mtE1E2s in CHO cells and compare their properties with their current wtE1E2. The mtE1E2 designs will… $117,831
Purdue University "Dr. Kuhn will carry out structural studies of hepatitis C virus (HCV) glycoproteins E1E2 and the virus particle. In addition, the binding of neutralizing… $302,360
Emory University "Background. This is a consortium proposal by Drs. S. Foung, B. Pulendran, and C. Walker for the Rational Design of Vaccines Against Hepatitis C Virus U19… $100,000
University Of Louisiana At Lafayette Dr. Francois Villinger, Director of the University of Louisiana at Lafayette New Iberia Research Center, will be leading the nonhuman primate Core for the… $297,147
Research Institute At Nationwide Children's Hospital The overall objective of the Project 2 workscope is to deliver a tetravalent T cell vaccine component that provides broad coverage of major global HCV genotypes… $40,000
Fred Hutchinson Cancer Center Project 2 will provide a vaccine component that elicits T cell-mediated immunity against the most dominant global HCV genotypes. This T cell component will be… $64,350
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Quick answers

Who received award U19AI159840?

U19AI159840 was awarded to The Leland Stanford Junior University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 1, 2021.

How much is award U19AI159840 worth?

$36,130,494 has been obligated on U19AI159840: $31,255,003 in federal funding and $4,875,491 in non-federal funding.

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