U01AI182179

A global syphilis vaccine targeting outer membrane proteins of Treponema pallidum - project abstract - A global syphilis vaccine targeting outer membrane proteins of Treponema pallidum. The scientific premise of this CRC proposal rests upon our three decades of work defining the molecular architecture of the outer membrane (OM) of Treponema pallidum subsp. pallidum (TPA), coupled with our successes combining bioinformatics, biophysical techniques, and localization methods with live TPA to topologically characterize TPA outer membrane proteins (OMPs) and define the syphilis spirochete’s ‘OMPeome’--its repertoire of OMPs.

The central hypothesis is that the principal targets for a syphilis vaccine reside within TPA’s repertoire of rare OMPs. The current application builds upon the work of the current CRC U19 grant awarded to the two MPIs of this proposal (Moody and Radolf). This proposal brings together the expertise in spirochetology (Univ. of Connecticut) and vaccine development (Duke Human Vaccine Institute) to develop vaccines targeting TPA OMPs.

The overarching hypothesis is that vaccines targeting TPA OMPs will elicit antibodies that can recognize intact treponemes, provide protection in animal models, and be producible using Good Manufacturing Practices (GMP) at the scale needed to perform a Phase 1 clinical trial. This CRC proposal will focus on two main aims: Aim 1) Selection of an ECL vaccinogen panel and production of ECL mAbs with functional activity, with subaim 1.1 of finalizing the ECL vaccinogen panel through robust preclinical animal studies (Univ. of Connecticut) and subaim 1.2 of producing ECL mAbs with functional activity (Duke Human Vaccine Institute), and Aim 2) Selection and optimization of an ECL vaccine platform, with subaim 2.1 of generating functional ECL-specific Abs using mRNA-LNP immunogens (Univ. of Pennsylvania), and subaim 2.2 of generating functional ECL-specific Abs using SPYVLPs (Univ. of Connecticut), to be compared in animal protection studies in subaim2.3.

Successful completion of the aims of this CRC U01 proposal will provide the preclinical data needed for an IND submission to the FDA, complete the process development for GMP production, and will result in the full design of a GMP campaign strategy and a plan for toxicology testing.

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 277132838 United States

Single Zip Code

Sexually Transmitted Infections (STI) Cooperative Research Centers (CRC): Vaccine Development (U01 Clinical Trial Not Allowed) (RFA-AI-23-008)

Amendment Since initial award the total obligations have increased 95% from $2,387,026 to $4,663,782.