Harnessing eATP-induced purinergic signaling to improve immunization strategies against viral infections

• Grant number: 24/13933-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 13, 2025
• End date: April 18, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Maria Regina D'Império Lima
• Grantee: Marcos Vinícios Pinheiro Cione
• Supervisor: Henrique Borges da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Mayo Clinic In Arizona, United States
• Associated to the scholarship: 23/15373-9 - Study of T cell-mediated immunity in experimental COVID-19: involvement of purinergic signaling, BP.DD

Abstract

Vaccination is essential in preventing viral infections and enhancing public health by reducing disease incidence and complications. However, vaccine efficacy varies due to factors such as the pathogen's nature, vaccine type, and individual immune response. Intranasal immunizations can improve the immune response by stimulating tissue-resident memory T cells (TRMs), promoting early virus elimination in secondary infections. While traditional vaccines generate a systemic response, strategies mimicking natural infection can foster more effective immunity. Understanding and manipulating immunological mechanisms that enhance vaccine responses is crucial. Purinergic signaling, involving ATP and the P2RX7 receptor, plays a key role in optimizing immune responses. Our hypothesis is that purinergic signaling through eATP sensing is vital in improving the immune response to immunization. To test this, we will conduct in vivo experiments immunizing mice intranasally with COVID-19 and influenza mRNA vaccines, using eATP as an adjuvant in some groups. We will track antigen-specific T cells and evaluate the eATP-P2RX7 axis using T-cell specific P2RX7-KO mice. Two-photon live imaging and the GRABATP sensor will identify cells responding to free eATP in lung tissue and examine P2RX7 activation and Ca2+ influx. The best immunization strategy will be validated with protection experiments using influenza and SARS-CoV-2 viruses. These models are available in the laboratory, aiming to advance understanding of purinergic signaling in immunization and develop new vaccine and therapeutic strategies for global public health.