Adjuvant activity of the filamentous hemagglutinin from Bordetella pertussis in fusion with the PspA antigen from Streptococcus pneumoniae

• Grant number: 17/01992-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2017
• End date: May 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Maria Leonor Sarno de Oliveira
• Grantee: Melissa Akemi Nishigasako
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil

Abstract

Streptococcus pneumoniae (pneumococcus) is one of the leading causes of pneumonia, meningitis and widespread infections in children worldwide. Recent estimates indicate that approximately 400,000 children under the age of five die annually from infections caused by S. pneumoniae around the world. Pneumococcal Surface Protein A (PspA) is a well-characterized antigen, conferring protection in animal models, representing a good alternative for current conjugate vaccines. Induction of protective immune response directed to PspA in animal models has already been described, but few low cost adjuvants for the composition of a subunit vaccine have been proposed to date. In previous studies, our group tested the use of the whole cell pertussis vaccine (wP) produced at the Butantan Institute, as adjuvant, in combination with PspA. The wP vaccine is one of the components of the DTwP (diphtheria, tetanus, cell pertussis) triple vaccine given to Brazilian children by the Ministry of Health at 2, 4 and 6 months of age, with a booster at 18 months and 5 years. Nasal immunization of BALB/c mice with a combination of PspA and wP induced high levels of anti-PspA antibodies and conferred protection against pneumococcal lethal infection as well as nasal colonization. Among the components involved in adjuvant activity are pertussis toxin (PT) and filamentous haemagglutinin (FHA), a protein abundant on the surface of B. pertussis. This project aims to evaluate the adjuvant capacity of the FHA (FHA44) N-ternimal region in fusion with PspA. For this purpose, expression and purification of the recombinant FHA44: PspA4 protein in E. coli system will be performed. FHA44: PspA4 antigen will be tested as a vaccine candidate against S. pneumoniae infection in mice.

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)

CASTRO, JULIA T.; OLIVEIRA, GIULIANA S.; NISHIGASAKO, MELISSA A.; DEBRIE, ANNE-SOPHIE; MIYAJI, ELIANE N.; SOARES-SCHANOSKI, ALESSANDRA; AKAMATSU, MILENA A.; LOCHT, CAMILLE; HO, PAULO L.; MIELCAREK, NATHALIE; et al. Evaluation of inactivated Bordetella pertussis as a delivery system for the immunization of mice with Pneumococcal Surface Antigen A. PLoS One, v. 15, n. 1, JAN 16 2020. (16/17258-9, 17/01992-8, 16/13134-3)