P01AI158571

Design and Development of a Pan-Betacoronavirus Vaccine - Abstract

Overall, compared to SARS-CoV-1 and MERS, the current SARS-CoV-2 virus is highly transmissible and to date has caused over 85,000,000 cases worldwide with over 1,800,000 deaths. With an endemic population of multiple other strains of CoVs in bats, rodents with intermediate hosts, civets, and pangolins, and because of the ability of CoVs to recombine, it is a certainty that new CoVs with infectious potential for humans will cause future human pandemics.

To address this problem in a focused and integrated way, this P01 team of virologists, immunologists, computational biologists, structural biologists, biophysicists, evolutionary biologists, and traditional vaccinologists will develop panbetacoronavirus (PanBetacov) vaccines, including Merbecoviruses (Group 2C), which gave rise to MERS, and Sarbecoviruses (Group 2B), which gave rise to SARS-CoV-1 and SARS-CoV-2, the three most deadly betacov human outbreaks.

The significance of this grant is that it will provide for PanBetacov vaccines for future epidemics that can be immediately available at the onset of a betacov pandemic, avoiding much of the human tragedy and social disruption caused by a pandemic.

The overall specific aims of the P01 are:

Aim 1. Develop and characterize immunogenicity of PanBetacov Sarbecovirus (Group 2B) vaccine candidates.

Aim 2. Determine Group 2B vaccine candidate protection capacity against Group 2B panel of viruses.

Aim 3. Develop PanBetacovMerbecovirus (Group 2C) vaccine candidates, determine their immunogenicity, cross-reactivity with other betacovs, and protection capacity against Group 2C panel of viruses.

This program project grant includes four projects. Project 1 will design vaccines in alphavirus replicon particle (VRP) vaccine system, develop and test P01 vaccines in their unique mouse CoV challenge models. Project 2 will use structure-based molecular modeling and monomer and multimer nanoparticle spike protein designs and test in wild-type mouse models. Project 3 will both design CoV vaccines and test vaccine designs expressed as mRNAs in liquid nanoparticles (LNPs). Project 4 will computationally design B and T cell PanBetacov vaccines.

This P01 proposes three cores: an administrative core, a biocontainment and immune monitoring core, and a non-human primate core.

Work in this P01 will provide PanBetacov vaccines to protect against escape mutants of SARS-CoV-2 in the current epidemic and will be available to protect society against new betacovs that might emerge to infect humans in the future.

Duke 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]

Durham, North Carolina 27710 United States

Single Zip Code

NIAID Investigator Initiated Program Project Applications (P01 Clinical Trial Not Allowed) (PAR-20-072)

Amendment Since initial award the End Date has been extended from 08/31/24 to 08/31/25 and the total obligations have increased 60% from $17,521,953 to $27,999,998.