U19AI159840

A Vaccine Design to Induce Protective B and T Cell Immunity against Hepatitis C Virus - Abstract

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 envelope 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 achieve 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 of eliciting 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.

The Leland Stanford Junior University

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Palo Alto, California 943041204 United States

Single Zip Code

Rational Design of Vaccines Against Hepatitis C Virus (U19 Clinical Trial Not Allowed) (RFA-AI-20-019)

Amendment Since initial award the total obligations have increased 400% from $2,377,023 to $11,896,603.