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 Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2019
• End date: September 07, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Maria Leonor Sarno de Oliveira
• Grantee: Giuliana Stephani de Oliveira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 22/05581-0 - Characterization of the activity of polyclonal anti-PCV13 antisera produced in mice with different susceptibility to infection with serotype 3 pneumococcal strains, BE.EP.DD

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)

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)

OLIVEIRA, GIULIANA S.; OLIVEIRA, MARIA LEONOR S.; MIYAJI, ELIANE N.; RODRIGUES, TASSON C.. Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies. VACCINES, v. 9, n. 11, NOV 2021. (17/26090-7, 18/25165-6, 19/15961-2, 19/06190-2, 21/04996-0)