Development and production of new pneumococcal vaccines based on recombinant proteins

• Grant number: 15/06255-6
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2015 - September 30, 2018
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Viviane Maimoni Gonçalves
• Grantee: Viviane Maimoni Gonçalves
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Eliane Namie Miyaji

Abstract

Streptococcus pneumoniae is an important human pathogen that causes diseases as pneumonia, meningitis and sepsis, which are responsible for high mortality rates worldwide. All current pneumococcal vaccines are based on capsular polysaccharides (PS), but their production cost is high and their coverage limited to the serotypes included in the formulation, which exerts a selective pressure that leads to serotype replacement in the population. Proteic vaccines have been proposed as an alternative to solve the aforementioned problems. The aim of this project is to develop, produce and evaluate a new pneumococcal vaccine of nanoparticles (NP) carrying pneumococcal recombinant proteins: pneumococcal surface protein A (PspA) and a hybrid molecule of PspA and genetically detoxified pneumolysin (PdT). High cell density cultivation of Escherichia coli and purification processes will be developed for production of high purity proteins with low endotoxin contend. The NP will be formulated as nanocomposite microparticle carriers for pulmonary delivery via dry powder inhalation. This vaccine would have the advantages of inducing serotype independent imune response and, as a dry powder, it would not need cold chain for storage and transportation. It is expected that NP would efficiently present the antigens to the pulmonary dendritic cells and protect against pneumonia. After immunization of mice, the imune response will be evaluated by the antibody titers in sera and in bronchoalveolar fluid and analysis of cytokines production in lung and spleen cells stimulated in vitro with the antigen. The efficacy of the vaccine will be evaluated by two models of intranasal challenge, one of non-invasive pneumonia and another of invasive pneumonia followed by death. (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)

RODRIGUES, TASSON C.; OLIVEIRA, MARIA LEONOR S.; SOARES-SCHANOSKI, ALESSANDRA; CHAVEZ-RICO, STEFANNI L.; FIGUEIREDO, DOUGLAS B.; GONCALVES, VIVIANE M.; FERREIRA, DANIELA M.; KUNDA, NITESH K.; SALEEM, IMRAN Y.; MIYAJI, ELIANE N.. Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection. PLoS One, v. 13, n. 1, JAN 23 2018. (15/06255-6, 14/25436-9)

KUNDA, NITESH K.; ALFAGIH, IMAN M.; MIYAJI, ELIANE N.; FIGUEIREDO, DOUGLAS B.; GONCALVES, VIVIANE M.; FERREIRA, DANIELA M.; DENNISON, SARAH R.; SOMAVARAPU, SATYANARAYANA; HUTCHEON, GILLIAN A.; SALEEM, IMRAN Y.. Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles. International Journal of Pharmaceutics, v. 495, n. 2, p. 903-912, NOV 30 2015. (15/06255-6, 12/04858-7)

FIGUEIREDO, DOUGLAS B.; CARVALHO, ENEAS; SANTOS, MAURICIO P.; KRASCHOWETZ, STEFANIE; ZANARDO, RAFAELA T.; CAMPANI, JR., GILSON; SILVA, GABRIEL G.; SARGO, CINTIA R.; HORTA, ANTONIO CARLOS L.; GIORDANO, ROBERTO DE C.; et al. Production and purification of an untagged recombinant pneumococcal surface protein A (PspA4Pro) with high-purity and low endotoxin content. Applied Microbiology and Biotechnology, v. 101, n. 6, p. 2305-2317, MAR 2017. (15/06255-6, 11/16605-3, 12/04858-7)