Development of next-generation vaccine against Staphylococcus aureus infections

• Grant number: 25/01617-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Preventive Veterinary Medicine
• Principal Investigator: Marcos Bryan Heinemann
• Grantee: Marcos Bryan Heinemann
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Claudia Dumont Oliveira ; Eduardo Milton Ramos Sanchez ; Fernando Nogueira de Souza ; Hiro Goto ; Luiza de Campos Reis ; Paulo Jorge Gonçalves de Bettencourt ; Sarne de Vliegher

Abstract

Staphylococcus aureus remains a significant challenge for the dairy industry worldwide due to its pathogenicity, contagiousness, persistence of infection, and the low cure rates associated with current therapies. Innovative approaches are urgently needed, especially considering S. aureus' role as a potential reservoir for epidemic human clones and its impact on food safety through the production of enterotoxins. In response to this challenge, this research proposal proposes the development of an innovative vaccine against intramammary infections caused by S. aureus, employing cutting-edge technologies in mRNA vaccines and multi-epitope vaccines based on reverse vaccinology. Building on previous findings from a serum immunoproteomics study, we have identified three conserved S. aureus proteins uniquely recognized by mastitis-resistant cows, indicating their potential as universal vaccine candidates. These proteins have demonstrated the ability to elicit robust immune responses in prior studies and will now be incorporated into mRNA vaccines and multi-epitope vaccines designed to stimulate TH1 and TH3 responses. The use of artificial intelligence will enable the prediction and incorporation of specific epitopes to enhance vaccine efficacy. Furthermore, this research proposal includes evaluating the impact of pre-contact with S. aureus on vaccine efficacy, a critical variable in immune response adaptation, as well as addressing the in vivo intramammary challenge. This research project is pioneering in its application of mRNA and multi-epitope vaccines based on reverse vaccinology for bovine mastitis, representing a significant advancement in developing an effective vaccine against intramammary infections by S. aureus in ruminants. (AU)