Characterization of the activity of polyclonal anti-PCV13 antisera produced in mice with different susceptibility to infection with serotype 3 pneumococcal strains

• Grant number: 22/05581-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: October 07, 2022
• End date: January 13, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Maria Leonor Sarno de Oliveira
• Grantee: Giuliana Stephani de Oliveira
• Supervisor: Liiseanne Pirofski
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Albert Einstein College of Medicine, United States
• Associated to the scholarship: 19/15961-2 - Caracterization of immune response to vaccines against Streptococcus pneumoniae in mice selected for high and low acute inflammatory responses, BP.DD

Abstract

Infections caused by Streptococcus pneumoniae mainly affect children and the elderly, causing around 197 million cases of pneumonia per year, mostly in developing countries. The pneumococcal capsule is an important virulence factor, protecting the bacterium against phagocytosis by host cells. The polysaccharides (PS) that compose the capsule show structural and antigenic variability, classifying pneumococcus into more than 90 serotypes. Currently licensed vaccines are based on these PS and demonstrated high efficacy against colonization and invasive diseases caused by the serotypes included in their formulation. However, despite the great contribution of PCVs to the reduction of pneumococcal diseases, some studies demonstrate an escape of serotype (ST) 3 bacteria in populations of all ages, vaccinated with PCV13. As a result, this serotype continues to be of great importance in invasive pneumococcal diseases. Different conditions that affect inflammatory responses may predispose to pneumococcal diseases. We have been studying the immune responses to vaccines in mice models of minimal (AIRmin) or exacerbated (AIRmax) acute inflammatory responses (AIR). Our results showed that immunization of AIRmin mice with PCV13 induce high levels of antibodies against pneumococcal polysaccharides 1 and 3, capable of binding to the surface of bacteria. Interestingly, the PCV13 vaccine protects AIRmin mice against infections with ST1 but not against infections with ST3 pneumococci. These results may suggest a failure in the anti-PS3 antibodies to drive the effective killing of the bacteria by immune cells.To verify this hypothesis, we propose to study the ability of anti-PCV13 antisera produced in AIRmin mice to induce phagocytosis, bacterial agglutination, and ST3 capsule shedding. (AU)