Research and development of oral administration vaccine viation for control of streptococosis in tilapies

• Grant number: 19/27857-5
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: February 01, 2021
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Matheus Martinez Faccioli
• Grantee: Matheus Martinez Faccioli
• Company: Farmacore Biotecnologia Ltda (FARMACORE)
• CNAE: Fabricação de medicamentos para uso veterinário ; Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: São Paulo
• Pesquisadores principais: Celio Lopes Silva ; Isabela Maria de Mello
• Associated researchers: Giovani Sampaio Gonçalves ; Mayara de Moura Pereira
• Associated research grant: 18/08591-1 - Research and development of vaccine for oral administration via feed for control of streptococose in tilapia, AP.PIPE
• Associated scholarship(s): 21/04543-5 - RESEARCH AND DEVELOPMENT OF VACCINE FOR ORAL ADMINISTRATION THROUGH RATION FOR THE CONTROL OF STREPTOCOCOSIS IN TILAPIA, BP.TT

Abstract

Fish farming is pointed as the segment responsible for the significant increase in the world supply of proteins of animal origin. Due to its water potential, Brazil has a large capacity, not only for production, but also for domestic consumption and fish exports. The growth of Brazilian tilapia production is quite significant, from 273,268 tons in 2005 to 640,500 tons in 2016. However, deficiencies in water and fish management and frequent water contamination compromise fish immunity and health. Controlling outbreaks of infections, especially those caused by Streptococcus agalactiae, is laborious, difficult, and expensive. This pathogen is responsible for high fish mortality and for over 30% of the sector's economic losses. The use of antimicrobials in water, while effective, burdens production and has disadvantages such as water contamination, the emergence of antibiotic-resistant bacterial strains, as well as serious consumer risks and serious regulatory impediments to export. Some types of vaccines are already commercialized, being those produced from attenuated bacteria the most used. These vaccines are administered by injection or by immersion baths. Despite having good immunogenicity, in both cases there are serious disadvantages of use, mainly related to the cost, amount used for immunization, and the difficulty in handling the animals. A good alternative is the development of a new vaccine for the sector. In the PIPE Phase 1 project (Process 2018 / 08591-1) Farmacore developed a microencapsulated vaccine formulation containing inactivated bacteria (S. Agalactiae) and a potent adjuvant to be administered orally along with feed. The concepts, assumptions, and technical-scientific challenges for establishing oral vaccine formulation for microparticle-coated or pelleted feed and stimulating intestinal mucosal immunity have been successfully overcome. The microparticles carrying the antigens are stable at acidic pH (do not break in the stomach of the animals) and are broken down at alkaline pH to release antigens in the fish intestine and to stimulate immunity of humoral and cellular mucosa specific to vaccine antigens. The main objective of this project is to continue the development and optimization of vaccine formulation in what has already been carried out in phase 1, and to demonstrate that formulation composed of feed-borne microparticles provides protective efficacy when fish are vaccinated and challenged with virulent S. Agalactiae strain (serotype 1b). As a plan of goals and methodologies, the project contemplates: bacteria production in 20L bioreactor scale; optimization and consolidation of conditions for microencapsulated vaccine formulation and feed coating or pelleting; establish appropriate immunization conditions and regimens to stimulate the innate and adaptive immune system; perform vaccine efficacy tests (vaccination followed by challenge with virulent bacterial strain). Farmacore participated in the 12th. Fapesp's PIPE High Tech Entrepreneurship Training (2019) on this oral fish vaccine project and the result was very important for the company and the project as it allowed for a direct and real interactive process with the Fapesp Program organizers and with potential customers and competitors. In this training it was possible evaluate the main components of the market; the business model; the learning with customers, partners and competitors; and learn to deal with the uncertainties of marketing innovation and creating entrepreneurship. The study also showed that the development of this vaccine will positively impact the national science and technology scenario, as well as bring significant benefits to the company, the market, society and the environment. (AU)