P01AI165066

Structural Vaccinology Guided Development of a Universal CoV Vaccine Utilizing Nucleic Acid Delivered Nanoparticles - Project Summary

In December 2019, a novel coronavirus named Sudden Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emerged. SARS-CoV-2 quickly spread globally, causing a pandemic disease known as Coronavirus Disease of 2019 (COVID-19). To date, there have been over 80 million infections and nearly two million deaths from COVID-19.

SARS-CoV-2 is the third beta coronavirus of zoonotic origin to cause human epidemics. It is similar to, but distinct from, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Sudden Acute Respiratory Syndrome Virus-1 (SARS-CoV-1), both of which caused outbreaks in this century.

While several candidate vaccines for SARS-CoV-2 have recently received emergency use authorization, there are ongoing challenges in controlling SARS-CoV-2. These challenges include the longevity of vaccine-induced responses, the emergence of mutations within SARS-CoV-2 strains, and the disproportionate morbidity and mortality among elderly patient populations.

Therefore, there is a great need for vaccine modalities that can address these challenges for SARS-CoV-2 vaccines and allow for targeting of multiple potentially pandemic coronaviruses simultaneously. Developing innovative vaccines that can provide broad immunity against known and newly emergent human coronaviruses is a key goal in the field.

The effects of antigen epitope diversity, density, valency, duration of antigen availability, and adjuvant-induced cytokine environment on the potency and breadth of vaccine-induced responses remain unclear. Nanoparticle vaccine formulations offer the ability to manipulate these variables.

We have generated self-assembling synthetic DNA-launched nanoparticle vaccines (DLNPs) that displayed increased immunogenicity compared to matched synthetic DNA launched monomer vaccines or protein-in-adjuvant formulations. We determined that synthetic DNA-launched nanoparticles increased both cellular and humoral responses.

Recombinant nanoparticle vaccines are thought to mediate their increased immunogenicity by persisting in the lymph nodes for extended periods compared to protein antigens. This promotes enhanced antigen presentation by follicular dendritic cells and increases germinal center formation and humoral immunity. The mechanisms behind cell-mediated responses to nanoparticle vaccines are less well understood but similar mechanisms may be at play.

We will capitalize on the novel in vivo assembling SyndLNP platform we have created to manipulate these variables and determine their effects on acute and long-term responses to CoV antigens in young and aged models.

The Wistar Institute Of Anatomy And Biology

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]

Philadelphia, Pennsylvania 191044205 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 08/31/25 to 08/31/27 and the total obligations have increased 34% from $2,626,814 to $3,517,692.