rBCG expressing PspA-PotD as a neonatal pneumococcal vaccine candidate: evaluation of the immune response and protection against Streptococcus pneumoniae

• Grant number: 18/10097-5
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): September 01, 2018
• Effective date (End): October 24, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Luciana Cezar de Cerqueira Leite
• Grantee: José Lourenço dos Santos Cunha e Silva
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Pneumonia remains as the leading infectious cause of death in children under 5 years old in the world, especially in developing countries. Despite the availability of pneumococcal conjugate vaccines, these are highly costly, progressively lose their efficiency in the evolutionary phenomenon of serotype substitution, and are not intended to immunize neonates: the most vulnerable infant group to pneumococcal infections. Thus, the project described here aims to create a protein-based neonatal pneumococcal vaccine by strategically using recombinant BCG as a live vector able to express a pneumococcal hybrid antigen (PspA-PotD). C57BL/6 adult mice will be immunized with the newly constructed rBCG-PspA-PotD lineage using the prime-boost strategy with booster dose of rPspA-PotD. This project will also establish, for the first time, a murine model of neonatal immunization to evaluate the efficacy of rBCG-based protein pneumococcal vaccines. Induced IgG antibodies will be quantified by ELISA using serum recovered from the animals, and their functional activity will be evaluated in vitro by opsonophagocytic assays. The cytokines produced and the cellular response profile will be evaluated by using stimulated culture of splenocytes from the immunized animals. The protection conferred by immunizations, both in the adult and neonatal models, will be assessed by the lethal Pneumonia challenge and the pneumococcal colonization of nasopharynx assays. The constructed rBCG-PspA-PotD is expected to maintain the adjuvant and immunogenic/protective properties of BCG and the parental antigens against S. Pneumoniae, respectively. We expect that the new neonatal model may indicate the potential of the new vaccine to extend protection to newborn infants. (AU)