One health approach to pursue the next-generation Staphylococcus aureus vaccine

• Grant number: 23/02512-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: May 01, 2025
• End date: April 30, 2030
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fernando Nogueira de Souza
• Grantee: Fernando Nogueira de Souza
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alessandro de Sá Guimaraes ; Alice Maria Melville Paiva Della Libera ; Ana Claudia Dumont Oliveira ; Audun Helge Nerland ; Bernardina Amorin Uscata ; Eduardo Milton Ramos Sanchez ; Henning Sorum ; Hiro Goto ; Jose Luis Capelo Martinez ; Luiza de Campos Reis ; Magnus Ake Gidlund ; Marcos Bryan Heinemann ; Marta Fonseca Martins ; Paulo Jorge Gonçalves de Bettencourt ; Robert Domingues ; Sarne de Vliegher ; Silvia Figueiredo Costa ; Thais Cristine dos Santos Soares

Abstract

Staphylococcus aureus threatens human and other animal health with the rising prevalence of antimicrobial-resistant strains and likewise raises economic concern and food security with S. aureus-causing bovine mastitis impacting the dairy industry, demanding a One Health approach. Staphylococcus aureus vaccination would represent a cost-effective public health intervention but has not yet been achieved. Previous vaccination efforts centered on antibody induction have so far failed, and moreover, growing evidence suggests the induction of T cell immune response essential to having a successful S. aureus vaccine. Then, it is crucial to pursue truly protective peptides to trigger the T cell response which, according to our previous findings, are poorly expressed by the bacteria but identifiable in the resistant hosts. In the present study, we will first use the powerful immunopeptidomics technology to reveal the repertoire of peptide antigens linked to the major histocompatibility complex of antigen-presenting cells presented to T cells. This search would be carried out in human and bovine hosts that are phenotypically and genotypically resistant to S. aureus. These peptides and their respective proteins will be further screened in silico to select promiscuous peptides for further synthesis to search for candidate vaccines. Furthermore, the immune response triggered by these selected peptides and proteins would be studied in-depth in humans and bovines in ex vivo studies using ELISpot, multiparameter assay, and high throughput single-cell transcriptomics. In vivo protection experiments are also planned in mouse models submitted to the S. aureus challenge. Hence, the present research proposal intends to be the basis for developing an effective next-generation S. aureus vaccine. (AU)