P01AI172525

Multidimensional Development of High-Affinity Anti-Glycan Antibodies to Fight Deadly Bacterial Infections - Abstract

The development of immunotherapies focused on the surface glycans of bacteria is hypothesized to be a potential paradigm shift in the fight against life-threatening and antibiotic-resistant bacteria, an emerging and increasing health concern for which therapeutic options are limited.

Our PO1 team will use chemistry to deconstruct and display bacterial glycan structures on an artificial platform to make them immunogenic and recognized by the immune system. Immune responses will be analyzed and dissected by bacteriologists, cellular and structural immunologists to determine the characteristics of what makes a vaccine or an antibody against glycans effective as an antibiotic and deployable in pre-clinical studies.

This program, which assembles some of the world experts in their respective fields, is ambitious and intends to pioneer the effort of placing immunotherapy next to chemotherapy for the treatment of bacterial infections. Our unique combination of chemistry-immunology-bacteriology-structural biology will provide the necessary mechanistic understanding of what qualifies a vaccine or an antibody to be effective in immunotherapy.

The team is already productive and has published the proofs of principle of the approach on which the science of this application is based: very high affinity antibodies can be produced against bacterial glycans exposed at the surface of antibiotic-resistant bacteria and are effective at combating infectious challenges.

We will expand our strategy to the surface glycans of three bacterial pathogens listed by WHO as "critical" or "high" priority: Staphylococcus aureus, Klebsiella pneumoniae, and Neisseria gonorrhoea.

The fundamental knowledge that we will gain from our studies should establish a very detailed blueprint of the immune recognition of glycans and glycopeptides by the immune system. The integration of the chemistry, immunology, and structural biology facets of the project directly into the bacteriology and in vivo models will identify glycan targets and strategies to initiate pre-clinical studies.

Scripps Research Institute

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]

La Jolla, California 920371000 United States

Single Zip Code

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

Amendment Since initial award the total obligations have increased 193% from $2,024,997 to $5,930,384.