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Evaluation of the immune response to vaccines against Streptococcus pneumoniae in mice with high susceptibility to infection

Grant number: 19/06190-2
Support Opportunities:Regular Research Grants
Duration: August 01, 2019 - January 31, 2022
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Maria Leonor Sarno de Oliveira
Grantee:Maria Leonor Sarno de Oliveira
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Streptococcus pneumoniae (pneumococcus) is responsible for diseases that kill around 400,000 children under 5 every year, worldwide. Commonly, bacteria colonize the upper respiratory tract of healthy individuals, establishing a commensal relationship with the host. Transmission between individuals occurs from this site. Occasionally, pneumococcus can invade sterile sites causing diseases such as pneumonia, septicemia, meningitis, otitis media and sinusitis. The main risk groups are children under 1 year of age and the elderly. Data from the literature and our group suggest that tissue inflammation may play an important role in the progression of pneumococcal infection. While a controlled inflammatory response appears to be definitive for bacterial control, exacerbated or persistent inflammation often seems to contribute to worsening. In a recent study, our group evaluated the effects of acute inflammatory response on pneumococcal respiratory infection in mice of AIRmax and AIRmin lines, genetically selected for low or exacerbated acute inflammatory response, respectively. The results showed that AIRmin mice are highly susceptible to pneumococcal infection and presented a continuous inflammatory response without control of bacterial load and inflammation. On the other hand, the AIRmax mice, which were more resistant to pneumococcal infection, had a high inflammatory response, that was rapidly controlled, resulting in a significant reduction of bacteria in the respiratory tract. The main differences observed in the innate immune response against pneumococcus were the absence of secretion of CXCL5 chemokine and matrix metalloproteinases and low influx of neutrophils in the lower respiratory tract of the AIRmin mice. Changes in the innate immune response may affect the adaptive immune response. The present project proposes the study of the adaptive immune response induced by vaccines based on polysaccharides (commercially available) and protein vaccines (experimental formulations studied in our laboratory) in AIRmax and AIRmin mice. In addition, we propose the evaluation of the protective capacity of these vaccine formulations in AIRmin mice, which were highly susceptible to pneumococcus. The data generated in this project may contribute to more effective strategies for the prevention of pneumococcal diseases in groups at risk. (AU)

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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, . (17/26090-7, 18/25165-6, 19/15961-2, 19/06190-2, 21/04996-0)

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