A novel selection and validadtion model for vaccine candidates against Staphylococcus aureus multi drug resistant

• Grant number: 22/15111-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2023
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Thiago Rojas Converso
• Grantee: Thiago Rojas Converso
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Associated researchers: Anders P Hakansson ; Lucas Miguel de Carvalho ; Michelle Darrieux Sampaio Bertoncini
• Associated scholarship(s): 24/08191-4 - IMMUNOLOGICAL ANALYSIS OF A PROTEIN BASED VACCINE GAINST Staphylococcus aureus MULTIDRUG RESISTANT, BP.PD; 24/03222-9 - EVALUATION OF NEW VACCINE CANDIDATES EXPRESSED BY INVASIVE FORMS OF MULTIDRUG-RESISTANT Staphylococcus aureus, BP.DR

Abstract

Staphylococcus aureus is a bacterium of great interest worldwide being responsible for high levels of hospital and community acquired infections, another important factor is that it is responsible for the rapid increasing of multidrug resistant strains. The infections are initiated by the host's asymptomatic colonization, where this bacterium start to form biofilms, a complex structure composed by bacteria and extracellular matrix, from biofilms, the bacterium can spread to other tissues causing several diseases. A recent report from WHO pointed that S. aureus is one of the most important bacteria for the development of prophylactic and therapeutics strategies. Even tough, several vaccine candidates have been proposed, until now there is no vaccine approved for humans against these pathogens. The failure on the development for effective vaccines is due to the lack of animal models and correlate of protection the fit on the physiological way the natural course of infection in humans. Besides that, most of the vaccine candidates were based on antigens capable to induce opsonizing antibodies - a mechanism that alone is not able to confer a long lasting immunity against this bacterium. Last, it is a consensus that vaccines based on isolated antigens won't be able to promote the higher levels of protection needed against these pathogens. Based on these limitations, we propose the development of a new selection and validation model for vaccine candidates against Staphylococcus aureus, our model combines bioinformatic, transcriptomic and proteomic analysis of the bacteria in two stages: from colonizing biofilms and biofilm-dispersed, virulent bacteria. The combination of techniques will allow us to identify molecules involved on the transition from infective virulent form the biofilm colonizing form, these molecules will be produced and evaluated in immunization experiments looking for protection in two different challenges routes. Also, it is our intention to produce chimeric molecules, fusing two or more candidates to produce more effective vaccine formulations based on more physiological infection models, which reflect the main pathogenesis steps on the host. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GUERRA, MARIA EDUARDA SOUZA; VIEIRA, BRENDA; CALAZANS, ANA PAULA CARVALHO THIERS; DESTRO, GIULIA VICENTE; MELO, KARINA; RODRIGUES, EMILLY; WAZ, NATALHA TEDESCHI; GIRARDELLO, RAQUEL; DARRIEUX, MICHELLE; CONVERSO, THIAGO ROJAS. Recent advances in the therapeutic potential of cathelicidins. FRONTIERS IN MICROBIOLOGY, v. 15, p. 11-pg., 2024-06-26. (22/15111-1)

DESTRO, GIULIA; VIEIRA, BRENDA; SOUZA GUERRA, MARIA EDUARDA; MELO, KARINA CRUZ; DARRIEUX, MICHELLE; CONVERSO, THIAGO ROJAS. Vaccination with BrpA, Biofilm Regulator Protein A, induce antibodies that affect biofilm formation in Streptococcus mutans. European Journal of Immunology, v. 54, p. 1-pg., 2024-09-01. (19/23566-6, 22/15111-1)

VIEIRA, BRENDA; DESTRO, GIULIA; GUERRA, MARIA EDUARDA SOUZA; MELO, KARINA CRUZ; HAKANSSON, ANDERS; DARRIEUX, MICHELLE; CONYERS, THIAGO ROJAS. Development of a new selection model for selection vaccine candidates against multidrug resistant Staphylococcus aureus. European Journal of Immunology, v. 54, p. 1-pg., 2024-09-01. (22/15111-1)