Study of bacterial components as adjuvants to protein vaccines against Streptococcus pneumoniae

• Grant number: 21/09919-3
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2022
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Maria Leonor Sarno de Oliveira
• Grantee: Maria Leonor Sarno de Oliveira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Lower respiratory tract infections are a major cause of deaths worldwide. Among the most important etiologic agents is Streptococcus pneumoniae (pneumococcus), responsible for the death of about 400,000 children under 5 years old worldwide. In addition to children, the elderly are also a risk group for pneumococcal infections. Polysaccharide vaccines are currently applied to children in several countries, including Brazil, and offer limited protection to the serotypes present in the formulations. Our research group has been studying vaccines composed of protein antigens, in particular the PspA (Pneumococcus Surface Protein A) antigen, for the development of serotype-independent immunity. In collaboration with the Pasteur Institute in Paris, we are testing a system based on the adenylate cyclase (CyaA) toxin from Bordetella pertussis for presenting PspA (CyaA-PspA) fragments to the immune system through immunization experiments in mice. The results already obtained indicated the formulations capable of promoting protection against some pneumococcus isolates. However, in order to improve the coverage of protection against different isolates, we propose in this project the study of new PspA fragments for presentation by the CyaA system. Furthermore, in order to increase the immunogenicity of CyaA-PspA proteins, we propose the evaluation of proteins containing the universal epitope PADRE (Pan DR-binding epitope) for stimulation of CD4+ T cells. Finally, in this project, we also propose the study of pneumococcal extracellular vesicles (EVs) as adjuvants for the PspA fragments. (AU)