U01AI182035

Development of a chimeric syphilis vaccine candidate to combat local, disseminated and congenital syphilis infection - project summary

In several high-income nations, including the United States, infectious syphilis has been resurgent for over two decades now, while syphilis is still endemic in low- and middle-income countries. Syphilis is therefore still a public global health concern, particularly because it can lead to neurological sequelae such as dementia and stroke-like syndromes, as well as cardiovascular manifestations potentially leading to death.

Furthermore, about half a million pregnancies are adversely affected by congenital transmission of the pathogen every year. The partial success of recent syphilis control campaigns promoted by the CDC and WHO clearly highlights the necessity of devising novel ways to control this serious infection. The availability of an effective syphilis vaccine could make a significant difference in the global effort to control the spread of this serious infection.

Over the last decade, our research programs have had the focus of identifying vaccine candidates among the surface-exposed antigens of the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum). These studies have led to the discovery that the T. pallidum repeat (TPR) protein family and the TP0751 vascular adhesin are critical proteins in the processes of chancre development/immune evasion and systemic dissemination, respectively.

When tested in immunization/challenge experiments in the rabbit model of syphilis, these antigens were shown to provide significant protection against infection. Furthermore, within these antigens, we have been able to pinpoint the epitopes necessary to generate a protective host response.

To reduce the complexity and production costs of our vaccine candidates, we have developed a chimeric protein platform where the non-functional loops of the TP0751 protein are exchanged with conserved epitopes from the TPR proteins. This approach provides a single construct that retains the critical TP0751 epitopes while allowing presentation of protective epitopes from other antigens in a stable and soluble scaffold.

This proposal encompasses the next phase of this research endeavor consisting of investigational new drug (IND)-enabling pre-clinical studies. To this end, we will create future generations of the chimera vaccine candidate to assess the level of induced immunoreactivity and protection, after which the vaccine delivery formulation will be optimized with the lead candidate by performing in vivo immunization/challenge experiments, toxicity and stability tests, and studies investigating compatibility with scale-up production.

Collectively these studies are anticipated to provide us with an efficacious syphilis vaccine candidate that is ready for clinical studies.

University Of Victoria

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]

Canada

Foreign

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 97% from $1,622,474 to $3,194,893.