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Nanoparticle pulmonary vaccine formulation based on lipossomes containing protein antigens from Streptococcus pneumoniae

Grant number: 17/26090-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2018
Effective date (End): October 25, 2021
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Eliane Namie Miyaji
Grantee:Tasson da Costa Rodrigues
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated scholarship(s):19/10497-6 - Production and characterization of liposomal nanoparticles containing pneumococcal protein antigens for pulmonary immunization against pneumococcal pneumonia., BE.EP.DR

Abstract

Streptococcus pneumoniae, or pneumococcus, is a component of the human microbiota, but in some cases it can cause diseases such as Sinusitis, Otitis Media, Pneumonia, Sepsis and Meningitis. Vaccination is the most effective strategy to control pneumococcal infections. The first generation pneumococcal vaccines are composed by free capsular polysaccharides (PS), inducing temporary protection. The second generation vaccines have increased effectiveness and are composed by PS conjugated to carrier proteins (PCVs). A decrease in the cases of invasive pneumococcal diseases (IPD) has been observed in the post-PCV era, including an effect in non-immunized individuals by herd immunity. On the other hand, an increase in the number of cases of IPD caused by serotypes not included in the PCVs has been reported. Besides that, PCV effectiveness against non-invasive disease, including Non-Bacteremic Pneumonia, is reported to be lower. A new generation of serotype-independent vaccines could improve protection against pneumococcal infections. Pneumococcal surface protein A (PspA) is an important candidate for vaccine development, since parenteral immunization with this protein was shown to be protective in different challenge models in mice. We now propose to test this antigen in a pulmonary immunization model to induce protection against Pneumococcal Pneumonia. The pulmonary administration is a promising model because the lungs have an extensive vascularization and a large population of antigen presenting cells (APCs) that can facilitate immunization. PspA shows some diversity and is classified in family 1 (clades 1 and 2), family 2 (clades 3, 4 and 5) and family 3 (clade 6). Since the majority of strains express PspA from families 1 and 2, a broad coverage vaccine should include proteins from both families. In fact, our group has recently tested a formulation with polymeric particles adsorbed with PspA from clade 4 (PspA4Pro) and protection was restricted to the same family. Our aim now is to produce and purify PspA from clade 1 (PspA1) and PspA4Pro for inclusion in liposome nanoparticles (LNP), formulated as nanocomposite microparticle carriers (LNP/NCMP PspA1+PspA4Pro) to evaluate immunogenicity and efficacy in vivo, using a murine model of pulmonary immunization. The induction of immune response will be assessed by measurement of antibodies in sera and brochoalveolar lavage fluid (BALF), analysis of cytokines in BALF, and analysis of the induction of T CD4+ resident memory cells in the lungs. The production of cytokines from spleen cells recovered from immunized animals and stimulated in vitro with PspA will also evaluated. The effectiveness of the immunization against Pneumonia will be assessed using an intranasal challenge model against 3 different pneumococcal strains. Bacterial load, cytokine release profile and cellular infiltrate in the lungs will be evaluated between 12 and 24 hours after challenge. (AU)