Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Experimental pneumococcal carriage enhances immunity and protects against homologous strain reacquisition.
• Understanding immunity against heterologous strains is crucial for developing effective vaccines and interventions.

Purpose of the Study:

• Investigate the role of naturally acquired pneumococcal protein and polysaccharide (PS)-specific immunity in protection against carriage acquisition.
• Utilize a heterologous challenge model to assess immune responses.

Main Methods:

• Healthy volunteers with natural pneumococcal colonization were challenged with a heterologous 6B strain after carriage clearance.
• Assessed 6BPS-specific, PspA-specific, and PspC-specific IgG and IgA plasma and memory B-cell populations before and after experimental pneumococcal inoculation.

Main Results:

• Heterologous challenge resulted in 50% carriage in volunteers with prior natural pneumococcal carriage.
• Protection from carriage was linked to a high number of circulating 6BPS IgG-secreting memory B cells at baseline.
• No associations were found between protection and baseline levels of 6BPS IgG, PspA-specific, or PspC-specific memory B cells or plasma cells.

Conclusions:

• Naturally acquired polysaccharide (PS)-specific memory B cells are associated with protection against pneumococcal carriage acquisition.
• Circulating IgG levels at the time of pneumococcal exposure were not associated with protection.
• Immune memory B cells targeting pneumococcal polysaccharides play a significant role in preventing colonization.