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Caracterization of immune response to vaccines against Streptococcus pneumoniae in mice selected for high and low acute inflammatory responses

Grant number: 19/15961-2
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): November 01, 2019
Effective date (End): March 31, 2022
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal researcher:Maria Leonor Sarno de Oliveira
Grantee:Giuliana Stephani de Oliveira
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Streptococcus pneumoniae (pneumococcus) is responsible for diseases such as Pneumonia, Septicemia and Meningitis, which cause the deaths of about 350,000 children under 5 every year, worldwide. Colonization precedes invasive diseases, which usually occur in situations of low immunity or previous inflammation, such as viral infections. Our group evaluated the effects of inflammation on respiratory pneumococcal infection in AIRmax and AIRmin mice, genetically selected for acute and exacerbated acute inflammatory response, respectively. The AIRmin mice presented increased susceptibility to pneumococcus in relation to the AIRmax mice, both in the models of invasive respiratory infection and in the model of restricted pulmonary infection. Among the characteristics analyzed, the AIRmin mice presented reduced secretion of CXCL5 chemokine and matrix metalloproteinases, as well as lower influx of neutrophils to the infection site, in response to the pneumococcal challenge. The present work started as a master project for the evaluation of the adaptive immune response to different vaccines against pneumococcus in the AIRmin mice. It was possible to observe that AIRmin mice are able to respond to protein vaccines, composed of the PspA antigen, with induction of functional antibodies, able to bind to the bacterial surface in vitro. Despite these results, the AIRmin mice were not protected against invasive pneumococcal challenge. These results were surprising, since anti-PspA antibodies are highly protective against pneumococcal infection in mice. Indeed, in passive immunization experiments, sera from vaccinated AIRmin mice were able to protect naive BALB/c mice, indicating that other factors such as phagocytosis and bacterial killing ability are deficient in AIRmin mice. For the continuity of the work, we propose the passage to the direct doctorate, aiming the analysis of the cellular populations infiltrated in the respiratory tract of vaccinated AIRmin mice, in comparison to the AIRmax and BALB/c mice; the establishment of pneumococcal phagocytosis assays in vitro from cells isolated from the three mouse lines and comparative analysis; the evaluation of the immunogenicity and protective capacity of commercial polysaccharide vaccines against pneumococcus in AIRmin mice. It is expected that the results obtained will contribute to the knowledge of mechanisms associated with high susceptibility to pneumococcus, which may result in a decrease in vaccine efficacy, and in the development of more adequate proposals for groups at risk. (AU)

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