Pneumococcal pneumonia and bacteremia model in mice for the analysis of protective antibodies

Area of Science:

• Microbiology
• Immunology
• Infectious Diseases

Background:

• Pneumococci colonize the nasopharynx and cause invasive diseases like pneumonia and bacteremia.
• Mouse models mimicking natural infection routes are valuable for studying antibody-mediated protection against Streptococcus pneumoniae.

Purpose of the Study:

• To establish and validate a mouse model for pneumococcal pneumonia and bacteremia.
• To investigate the protective efficacy of human antibodies against pneumococcal infections in this model.

Main Methods:

• Intranasal inoculation of mice with various Streptococcus pneumoniae serotypes.
• Passive immunization with human IgG preparations.
• Assessing protection against infection, bacteremia, and mortality.
• Adsorption assays using homologous capsular polysaccharides and cell wall polysaccharides (CWPS).
• In vitro opsonophagocytic assays to correlate with in vivo protection.

Main Results:

• Intranasal challenge with serotypes 1, 3, 6A, and 8 resulted in lethal pneumonia and bacteremia; serotype 6B caused mild infection.
• Passive immunization with human IgG dose-dependently protected against bacteremia (except for serotype 3) and cleared lung infections for serotypes 1, 6A, and 8.
• Antibody protection was abolished by adsorption with homologous capsular polysaccharides but not by CWPS.
• A strong correlation was found between in vivo protection and in vitro opsonic activity.

Conclusions:

• The developed mouse model accurately reflects pneumococcal infection and is suitable for studying antibody-mediated protection.
• Human antibodies, particularly those targeting capsular polysaccharides, are crucial for protection against pneumococcal pneumonia and bacteremia.
• This model can be utilized to analyze antibody characteristics and evaluate novel pneumococcal vaccine candidates.