U18FD008342

Validation of ENDOPEP-MS for qualitative detection of BONT/A, /C, /CD, /D, and /DC in animal specimens and feed.

- Project summary/abstract

Botulism is a serious paralytic disease that affects both humans and animals which is caused by botulinum toxins (BONTS).

Animal botulism outbreaks in farm animals, in particular, not only affects animals but also result in financial losses for the industry and increases the risk of human exposure to BONTS through animal products such as milk.

To prepare for a response to the future outbreaks, a fast, sensitive, and reliable detection method for BONTS is needed.

The ENDOPEP-MS method is one of the most promising methods that has been used for confirmation of human botulism by the Centers for Disease Control and Prevention (CDC) for years.

However, a comprehensive validation study of the ENDOPEP-MS for animal specimens and feed is lacking, and none of the veterinary diagnostic laboratories in the US have standard procedures for performing this method.

To fill the knowledge gap, our team at the California Animal Health and Food Safety Laboratory (CAHFS), a founding member of VET-LIRN, is proposing a comprehensive validation study of the ENDOPEP-MS for qualitative detection of BONT/A, /C, /CD, /D, and /DC in animal specimens and feed.

Our study has three specific aims as follows.

Specific Aim #1: To validate the ENDOPEP-MS for qualitative detection of BONT/A, /C, /CD, /D, and /DC in animal specimens and feed.

We will validate and compare the developed method to the standard mouse bioassay (MBA) using toxin-spiked samples and archived samples collected during natural botulism cases.

The sample matrices include but are not limited to animal sera, liver, gastrointestinal contents, and feed.

Specific Aim #2: To develop monoclonal antibodies for the toxin extraction step in the ENDOPEP-MS method.

Monoclonal antibodies are key for the ENDOPEP-MS to achieve selectivity toward BONT serotypes in samples.

Since there is currently only one source of the monoclonal antibodies in the US, we will collaborate with Dr. Christina Tam at United States Department of Agriculture (USDA) and develop new monoclonal antibodies for the method.

Specific Aim #3: To assess the effectiveness of polyclonal antibodies for the toxin extraction step in the ENDOPEP-MS method.

The limited source of monoclonal antibodies can delay research development and adoption of this method, an issue we have experienced ourselves.

Alternately, polyclonal antibodies are commercially available but the ability of polyclonal antibodies for BONTS extraction has not been completely explored.

We will complete this knowledge gap by investigating the capability of polyclonal antibodies for extraction of BONT/C, /CD, /D, and /DC.

If this project is funded and achieved, the lethal and time-consuming MBA that has been performed at CAHFS for close to 30 years can be avoided.

Our laboratory, as part of the VET-LIRN, will have the ENDOPEP-MS ready to support botulism testing during outbreaks and large-scale animal feed emergency events.

Davis University Of California

TO ASSIST INSTITUTIONS AND ORGANIZATIONS, TO ESTABLISH, EXPAND, AND IMPROVE RESEARCH, DEMONSTRATION, EDUCATION AND INFORMATION DISSEMINATION ACTIVITIES, ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS), BIOLOGICS, BLOOD AND BLOOD PRODUCTS, THERAPEUTICS, VACCINES AND ALLERGENIC PROJECTS, DRUG HAZARDS, HUMAN AND VETERINARY DRUGS, CLINICAL TRIALS ON DRUGS AND DEVICES FOR ORPHAN PRODUCTS DEVELOPMENT, NUTRITION, SANITATION AND MICROBIOLOGICAL HAZARDS, MEDICAL DEVICES AND DIAGNOSTIC PRODUCTS, RADIATION EMITTING DEVICES AND MATERIALS, FOOD SAFETY AND FOOD ADDITIVES. THESE PROGRAMS ARE SUPPORTED DIRECTLY OR INDIRECTLY BY THE FOLLOWING CENTERS AND OFFICES: CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER), CENTER FOR DRUG EVALUATION AND RESEARCH (CDER), CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH), CENTER FOR VETERINARY MEDICINE (CVM), CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN), NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH (NCTR), THE OFFICE OF ORPHAN PRODUCTS DEVELOPMENT (OPD), THE CENTER FOR TOBACCO PRODUCTS (CTP), AND OFFICE OF REGULATORY AFFAIRS (ORA), AND THE OFFICE OF THE COMMISSIONER (OC). SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAMS: TO STIMULATE TECHNOLOGICAL INNOVATION, TO ENCOURAGE THE ROLE OF SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION BY MINORITY AND DISADVANTAGED PERSONS IN TECHNOLOGICAL INNOVATION. FUNDING SUPPORT FOR SCIENTIFIC CONFERENCES THAT ARE RELEVANT TO THE FDA SCIENTIFIC MISSION AND PUBLIC HEALTH ARE ALSO AVAILABLE.

93.103 - Food and Drug Administration Research

FDA Office of Acquisition and Grant Services (OAGS) [HHS - FDA]

Food and Drug Administration (FDA) [HHS]

Davis, California 95616 United States

Single Zip Code

Vet-LIRN Capacity-Building Project and Equipment Grants (U18) (PAR-23-202)

Amendment Since initial award the total obligations have increased 100% from $49,689 to $99,378.