Development of a nanoparticle delivery system to the nasal mucosa for the StreptIncor vaccine against Streptococcus pyogenes

• Grant number: 24/15528-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Jorge Elias Kalil Filho
• Grantee: Jorge Elias Kalil Filho
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: CESAR MANUEL REMUZGO RUIZ ; Edecio Cunha Neto ; Keity Souza Santos ; Koiti Araki ; Luiza Guglielmi ; Marco Antonio Stephano ; Verônica Porto Carreiro de Vasconcellos Coelho ; Vivian Leite de Oliveira

Abstract

Lancefield Group A streptococci are responsible for several invasive and immune-mediated diseases, colonizing the epithelial surfaces of the respiratory tract and skin. Despite the efficacy of current antibiotic treatments, over 200 new strains have already been identified, with a high likelihood of bacterial resistance to treatment. Therefore, an effective vaccine against Streptococcus pyogenes is of utmost necessity. The StreptIncor (SI) vaccine developed by our group, administered systemically in the form of a synthetic peptide, is in the late stage of preclinical development (TRL5) and beginning of phase I clinical trials. However, given the tropism of this pathogen for mucosal epithelium, a nasal immunization strategy may result in better initiation of immune responses. This project aims to study a vaccine platform for S. pyogenes infections in the oropharynx. The first phase involves morphological, surface, and thermal analyses of innovative vaccines containing the StreptIncor delivered via nanoscale systems (NP), which have demonstrated promise in preclinical studies conducted by our team and collaborators. In the second phase, the research will focus on assessing the immunological potency of the SI+NP vaccine instilled nasally in murine models. In the final phase, we will explore the feasibility of utilizing the investigated vaccines as booster doses, evaluating specific immune responses and cellular parameters, to determine the optimal conditions for effective induction of systemic and mucosal immunity. This project presents innovative features, influencing the translation of fundamental science into clinical interventions, and paves the way for the nucleation of a new direction within the Incor-HCFMUSP research line. (AU)