Immunotherapy against experimental Cryptococcosis: a vaccine strategy associated with immunostimulators that recognize carbohydrate

• Grant number: 18/19949-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2019
• End date: October 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Thiago Aparecido da Silva
• Grantee: Patrícia Kellen Martins Oliveira Brito
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Fungal infections commit millions of lives each year and the Cryptococcosis has important relevance because affects immunocomprised and immunocompetent individuals, representing one of the main causes of worldwide morbidity and mortality among HIV+ individuals. The antifungal drugs are used as clinical treatment against Cryptococcosis, however most of agent’s toxic to fungi can cause side effects in humans. Thus, big research groups have innovative approaches for treatment using adjuvants and vaccine strategies for targeting components of the fungal cell-surface and -cytosol, promoting partial protection against Cryptococcosis. Considering the importance of different approaches for vaccination against Cryptococcosis and the administration of immunostimulatory agents, the current proposal aims to induce the immune innate cells activation to improve the development of a antibody-mediated immunity. For that, we will standardize the immunization protocol by administration of TLR2/CD14 agonist, ArtinM lectin, or Dectin-1 agonist, ²-glucan peptide, to induce the cell activation of the innate immunity, and after we will perform the vaccination with attenuated C. gattii. The periods related to administration of the immunostimulatory agents and the vaccine will be defined by a specific antibody titration assay against components of the cell wall followed by specific objectives into the current proposal. To contribute in the immunization protocol described above, an immunotherapeutic strategy based in the administration of anti-GXM monoclonal antibody during the course of C. gattii infection will be applied. After the association between immunization protocol and therapy with anti-GXM antibody the progression of Cryptococcosis will be correlated to the host immune response. Our proposal is within the scientific consensus related to new vaccination approaches in association with immunostimulating agents, which focus in the development of a cellular and humoral immune response against Cryptococcosis. The description of the TLR2 and Dectin-1 agonists as an important immunostimulatory agents in the immunization protocol against Cryptococcosis, and the effect of the therapeutic administration of anti-GXM antibody on the Cryptococcosis, will open new perspectives to evaluate the association of the various immunotherapy strategy against Cryptococcosis and other invasive fungal infections. (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)

DE CAMPOS, GABRIELA YAMAZAKI; OLIVEIRA, RAQUEL AMORIM; MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. Pro-inflammatory response ensured by LPS and Pam3CSK4 in RAW 264.7 cells did not improve a fungistatic effect on Cryptococcus gattii infection. PeerJ, v. 8, NOV 25 2020. (16/17037-2, 18/21708-5, 18/18538-0, 18/19949-4)

MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; DE CAMPOS, GABRIELA YAMAZAKI; GUIMARAES, JULIA GARCIA; DA COSTA, LETICIA SERAFIM; DE MOURA, EDANIELLE SILVA; LAZO-CHICA, JAVIER EMILIO; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. Adjuvant Curdlan Contributes to Immunization against Cryptococcus gattii Infection in a Mouse Strain-Specific Manner. VACCINES, v. 10, n. 4, p. 26-pg., 2022-04-01. (19/13979-1, 19/09261-8, 18/18538-0, 19/09260-1, 18/19949-4, 16/04877-2, 18/21708-5, 19/26074-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BRITO, Patrícia Kellen Martins Oliveira. Immunomodulation via carbohydrate ligands in a vaccine strategy helps in the control of Cryptococcus gattii infection. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.