U01AI182180

Development of a recombinant protein vaccine for Chlamydia trachomatis - there is a clear need for a vaccine to protect against Chlamydia trachomatis (CT), a sexually transmitted bacterium causing an ongoing epidemic associated with reproductive complications.

IFN-producing CD4 T cells (Th1 & Th1/17 cells) are required for protection from CT, which grows and replicates intracellularly, whereas antibodies provide complementary protection in the presence of IFN.

Our studies of Chlamydia-infected women and mice have identified Chlamydial Protease Activity Factor (CPAF) as an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, making it a strong vaccine candidate.

Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity requires potent adjuvants and mucosal vaccination to imprint FGT homing or generate resident memory T cells.

Our preliminary data indicate that intranasal immunization of female mice with CPAF conjugated to the TLR9 agonist, CPG, combined with the STING agonist, cyclic-di-AMP (CDA) in the squalene oil-in-water nanoemulsion AddaS03 (AS03), induces high levels of CPAF-specific CD4 T cells and protection from infection and pathology.

Our novel covalent CPAF-adjuvant conjugation approach enhances antigen-presenting cell activation through coincident stimulation leading to the potential for dose sparing, reduced toxicity, enhanced immunogenicity, superior efficacy, and reduced cost of goods.

This proposal incorporates a tiered approach to determine if refinements using innovative new generation TLR7/9 and STING agonists delivered via mucosal routes will enhance protection via the following specific aims: Aim 1. Complete product development activities of 2nd generation dual agonist CPAF vaccines. (I) Refine the multi-adjuvant CPAF-CPG+CDA+AS03 vaccine. (II) Covalently conjugate TLR7, -9 and STING agonists to CPAF. (III) Perform in-vivo formulation, toxicology, and preliminary immunogenicity analysis of candidate vaccines.

Aim 2. Evaluate efficacy of the 2nd generation candidates in the female murine challenge model and immunogenicity in male mice. (I) Determine most efficacious vaccine regimen (candidate and route). (II) Determine protection against female infertility and vaccine immunogenicity in males. (III) Determine duration of humoral and cell-mediated responses by top candidate, and the contribution of additional boosting.

Aim 3. Vaccine process development. (I) Optimize upstream production, downstream purification, and conjugation of CPAF. (II) Develop analytical assays and qualify as suitable for intended use. (III). Develop formulation and evaluate vaccine stability. (IV) Conduct a non-GLP toxicology assessment of the final vaccine candidate.

Accomplishing these three specific aims will result in a Chlamydia vaccine candidate ready for tech transfer to a qualified CMO, GMP production, and early-phase human clinical trials.

University Of North Carolina At Chapel Hill

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]

Chapel Hill, North Carolina 27599 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 End Date has been extended from 01/31/29 to 03/31/29 and the total obligations have increased 120% from $1,763,417 to $3,885,058.