Development of vaccines against Streptococcus pneumoniae using bacterial components as adjuvants for the PspA antigen

• Grant number: 21/05671-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: October 01, 2021
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Maria Leonor Sarno de Oliveira
• Grantee: Giovanna de Brito Carneiro
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• Associated scholarship(s): 22/06501-0 - Expression of PspA fragments in the CyaA vector for the development of a broad-coverage vaccine against Streptococcus pneumoniae, BE.EP.DD

Abstract

Lower respiratory tract infections are a major cause of death worldwide. Streptococcus pneumoniae (pneumococcus) is among the most important etiologic agents, being responsible for the annual death of about 400,000 children under 5 years old worldwide. The elderly are also a high risk group for pneumococcal infections. Polysaccharide vaccines are currently applied to children in several countries, including Brazil, but their protection are limited to the serotypes included in the formulations. Aiming at the development of formulations that provide serotype-independent protection, our research group has been testing protein antigens, such as the Pneumococcal Surface Protein A (PspA). In collaboration with the Pasteur Institute of Paris, an antigen presenting system based on adenylate cyclase (CyaA) toxin from Bordetella pertussis was constructed for presentation of PspA fragments (CyaA-PspA) to the immune system. The results obtained so far have shown the most effective constructions and formulations capable of providing broad protection for different isolates. However, in order to improve cross-protection against different isolates, we propose in this project the study of new fragments for cloning in 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 CD4+ T cells stimulation. Lastly, in this project, we also propose the study of pneumococcal extracellular vesicles (EVs) as adjuvants for the PspA antigen. (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)

CARNEIRO, GIOVANNA BRITO; CASTRO, JULIA TAVARES; DAVI, MARILYNE; MIYAJI, ELIANE NAMIE; LADANT, DANIEL; OLIVEIRA, MARIA LEONOR SARNO. Immune responses and protection against Streptococcus pneumoniae elicited by recombinant Bordetella pertussis adenylate cyclase (CyaA) carrying fragments of pneumococcal surface protein A, PspA. Vaccine, v. 41, n. 28, p. 13-pg., 2023-06-17. (19/25853-2, 16/13134-3, 21/05671-7, 16/50296-1, 16/17258-9, 17/01701-3)

CARNEIRO, GIOVANNA B.; YERNENI, SAIGOPALAKRISHNA S.; CHINAIA, KATHARYNE; ARAUJO, ADRIANO P.; SMITH, BAILEY E.; EUTSEY, RORY; CAMPHIRE, SHAW; WERNER, SARAH; CAMPBELL, PHIL; MIYAJI, ELIANE N.; et al. Protection induced by Streptococcus pneumoniae extracellular vesicles against nasal colonization and invasive infection in mice and the role of PspA. Vaccine, v. 44, p. 13-pg., 2024-12-16. (19/25853-2, 21/05671-7, 21/09919-3)