Performing Department
Poultry Science
Non Technical Summary
The capacity of Salmonella to successfully colonize and transmit in chickens is the most critical feature contributing to public food safety concerns due to consumption of Salmonella-contaminated chicken meat. Although a great deal of effort has been made toward understanding gut colonization by Salmonella, the mechanisms underlying horizontal transmission remain largely unknown. In this project, we will develop a novel vaccination strategy to control Salmonella in chickens based on the two key concepts recently developed by our team. In Objective 1, we will optimize and evaluate the use of DNA-based aptamer adjuvant targeting CD40 as a universal bivalent system. In Objective 2, we will use a powerful functional genomics tool, transposon sequencing, to identify genetic factors in Salmonella Typhimurium required for horizontal transmission. In Objective 3, the novel vaccination strategy developed in Objective 1 will be adopted to target the transmission factors identified in Objective 2 to reduce horizontal transmission in a chicken flock. The results of this project will provide previously unknown mechanistic insights on Salmonella horizontal transmission and a versatile and universal vaccination platform that can be used for effective control of the horizontal transmission and thus the prevalence of Salmonella in a chicken flock.
Animal Health Component
100%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Goals / Objectives
The long-term goal of this project is to reduce the prevalence of Salmonella serovars in broiler chickens at the early pre-harvest stage by developing a novel vaccination strategy that reduces horizontal transmission within a chicken flock. Salmonella continues to be a great public health concern and the consumption of chickens remains to be the major source of Salmonella infection for the human population. Despite the great efforts that have been made to reduce this burden, its overall negative impact remains unhampered and this situation demands the development of novel strategies that can cripple Salmonella colonization in chicken flocks. Our team has proved CD40 targeting is a universal strategy that can effectively enhance vaccination efficacy in chickens using agonistic CD40-specific monoclonal antibodies through experimental demonstration of its efficacy against avian influenza virus and Clostridium perfringens. More recently, our team expanded a way to apply this strategy at a commercial scale, overcoming the disadvantages associated with the use of monoclonal antibodies. In brief, we developed single-stranded DNA aptamers with specific binding affinity to the chicken CD40 extracellular domain, which were then utilized to produce rolling circle amplification (RCA) products that incorporate two of the most promising anti-CD40 aptamers (SEQ3 and SEQ4) in hundreds of copies. When this RCA product was conjugated to an antigen of interest, it significantly enhanced immune response to the antigen in broiler chickens. Most vaccines used to control Salmonella have been exclusively focused on reducing gut colonization, while horizontal transmission is another critical aspect contributing to Salmonella prevalence in final chicken meat products. This is largely due to the fact that our understanding of the horizontal transmission of Salmonella is limited, particularly in terms of the bacterial factors contributing to the process. In this project, our team will overcome this barrier by performing comprehensive screening to identify transmission factors of S. Typhimurium using a functional genomics tool, transposon sequence (Tn-seq). Once the transmission factors are identified and validated, we will develop the novel enhanced vaccination platform based on the aptamer RCA adjuvant that is designed to reduce horizontal transmission. We have the following 3 objectives to accomplish the long-term goal of this project.Objective 1. Evaluation of the universal CD40-targeting aptamer RCA adjuvant platform as a bivalent systemObjective 2. Comprehensive identification of the genetic factors in S. Typhimurium required for gut colonization and horizontal transmissionObjective 3. Vaccination targeting surface-exposed transmission factors in S. Typhimurium to reduce horizontal transmission in a chicken flockEach component/technique within this research proposal has been previously verified independently, but the union of these components to develop a more industry-functional and affordable system has yet to be accomplished. Successful completion of the proposed research will: 1) bring the universal aptamer RCA platform forward as a versatile and effective vaccination method that can be used for multiple pathogens in the poultry industry, 2) provide a safe option to vaccinate chickens against Salmonella, and 3) potentially serve as a multivalent/multi-serogroup Salmonella vaccination method, capable accommodating new outbreak strains.
Project Methods
Efficacy of an optimized DNA-based aptamer adjuvant targeting CD40 as a universal bivalent system will be investigated. Transposon sequencing will be used to identify genetic factors in Salmonella Typhimurium required for horizontal transmission. The the novel vaccination strategy developed will be adopted to target the transmission factors identified to reduce horizontal transmission in a chicken flock. This will be validated in laboratory-scale in vivo studies.