Study of apoferritin-chitosan delivery system containing the EGFRvIII peptide as a proposed peptide vaccine: Obtainment, characterization and in vitro evaluation of the release and immune response profile

• Grant number: 25/04693-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: April 30, 2027
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Fabiana Testa Moura de Carvalho Vicentini
• Grantee: Maya Borges Scrideli
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The subunit vaccines, such as peptide vaccines, have been increasingly studied for prophylactic use or for the treatment of infectious diseases, autoimmune diseases, tumors, among others. The major challenge involving the use of vaccines, as a therapeutic strategy for tumors, is related to the tumor microenvironment, which allows cancer to escape from immune surveillance. In this way, the peptide vaccine would act to stimulate the adaptive immune system to recognize and kill tumor cells, promoting recognition of the peptide by antigen-presenting cells. The use of peptides as antigens, although presenting important advantages, faces the challenge of low immunogenicity when used alone, requiring an adjuvant that contributes to the process of activating the immune system. There are several platforms within nanotechnology that have the potential to carry peptide antigens and also act as adjuvant systems, such as synthetic nanoparticles such as liposomes, exosomes, VLPs (virus-like particles), endogenous proteins, among others. Ferritin, a constitutive protein involved in the iron storage and transport, has natural properties such as being a biological nanoparticle that support the proposal for its use as a platform for antigen delivery. Chitosan nanoparticles, in turn, are also capable of increasing the immunological activity in relation to the antigen, favoring the targeting of antigen-presenting cells and causing the secretion of inflammatory factors by macrophages, thus regulating the immune response. In view of this, the present project aims to develop a delivery system based on apoferritin-chitosan to carry the EGFRvIII antigen as a proposed peptide vaccine that presents characteristics that justify its future investigation in a melanoma model. The EGFRvIII antigen was chosen considering that abnormal activation of the gene that synthesizes EGFR is associated with tumor progression and reduced survival in several types of cancer, making it an important target. Furthermore, EGFRvIII is a mutation of EGFR responsible for the formation of PEPvIII, a specific epitope of tumor cells with a high incidence in melanomas. (AU)