R01AI177144

Development of MECVAX, a Cross Protective Subunit Vaccine for ETEC - Project Summary

Diarrhea is the second leading cause of death in children aged <5 years in developing countries, more than AIDS, malaria, and measles combined. Our long-term goal is to develop effective vaccines against diarrheal bacteria.

The objective of this industrial partnership project is to combine expertise and leadership from academic vaccine research and industrial vaccine development and manufacturing to accelerate the development of MECVAX, a multivalent cross-protective subunit vaccine for enterotoxigenic Escherichia coli (ETEC). ETEC bacteria are one of the top five causes of children's diarrhea and the most common cause of travelers' diarrhea. ETEC is listed as a Category B priority pathogen (NIH) and a serious threat of antibiotic resistance (CDC), and causes >220 million diarrhea clinical cases annually, resulting in stunting and poor cognitive development in diarrheal children, 1,065,000 years lost due to disability (YLD), 6,894,000 years to disability-adjusted life-years (DALY), and about 100,000 deaths (many are children <5 years). ETEC is also a primary cause of diarrhea in young animals and causes significant economic losses worldwide.

Currently, there are no licensed vaccines against ETEC diarrhea. The development of effective vaccines for ETEC is a top priority for WHO, UNICEF, and many other public health institutions.

By applying an innovative vaccinology platform, we have constructed two polyvalent proteins and developed a protein-based multivalent ETEC vaccine candidate, MECVAX. MECVAX is the only ETEC vaccine candidate that induces protective antibodies against both ETEC toxins (LT and STa) and the seven most important ETEC adhesins (CFA/I, CS1 - CS6). Since ETEC bacteria producing LT and/or STa toxin are associated with all ETEC diarrhea cases and strains expressing adhesin CFA/I or CS1 - CS6 cause >66% of ETEC clinical cases, the synergy of antitoxin and anti-adhesin immunity from MECVAX provides truly broad protection against ETEC children's diarrhea and travelers' diarrhea. MECVAX is demonstrated to broadly protect against ETEC clinical diarrhea and colonization of small intestines preclinically.

The central goal of this milestone-oriented vaccine development project is to optimize MECVAX vaccine formulation, analytical development, and production processing. The rationale is that the completion of this application will identify MECVAX optimal formulation, optimize upstream and downstream processing and analytical development, and manufacture vaccine CGMP products - essential to accelerate MECVAX development.

To achieve these goals, we will:

1) Evaluate MECVAX protection against ETEC adherence and enterotoxicity at different antigen doses, adjuvants, buffers, and shelving conditions.
2) Optimize analytical assays and upstream and downstream processing.
3) Manufacture and test MECVAX master cell banks.
4) Perform product production engineering runs and submit MECVAX pre-IND application.

The positive impact is that an effective ETEC vaccine will save nearly 100,000 lives and prevent >200 million diarrheal clinical cases each year, and reduce long-term negative nutritional and developmental impacts.

University Of Illinois

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]

Urbana, Illinois 618013620 United States

Single Zip Code

Partnerships for Development of Vaccines Against Select Enteric Pathogens (R01 Clinical Trial Not Allowed) (RFA-AI-22-037)

Amendment Since initial award the total obligations have increased 194% from $1,170,694 to $3,440,502.