Genomic and panproteomic analysis of the development of infant immune responses to antigenically-diverse pneumococci

Area of Science:

• Immunology
• Microbiology
• Pediatrics

Background:

• Streptococcus pneumoniae (pneumococcus) is a common bacterium residing in the nasopharynx, capable of causing respiratory infections.
• Understanding the development of immune responses to pneumococcal antigens in early life is crucial for predicting and preventing disease.

Purpose of the Study:

• To characterize the development of the immunoglobulin G (IgG) antibody repertoire against pneumococcal antigens from birth to 24 months of age.
• To investigate the factors influencing individual differences in antibody responses, including maternal antibodies and antigen exposure.

Main Methods:

• A prospective cohort study of 63 children was conducted, with samples collected from birth to 24 months.
• A panproteome array was utilized to measure IgG antibody levels against a wide range of pneumococcal antigens.
• Genomic data on nasopharyngeal colonization was integrated to correlate immune responses with bacterial exposure.

Main Results:

• Infant IgG levels were highest at birth due to maternal antibody transfer, with distinct kinetics for responses to individual antigens.
• Stable individual differences in antibody response strength, linked to maternal IgG, were established by 6 months.
• Unique antibody profiles emerged by 12 months, boosted by re-exposure, with some antigens eliciting stronger responses in adults.

Conclusions:

• The study highlights significant heterogeneity in infant IgG responses to pneumococcal antigens, influenced by maternal factors and antigen exposure.
• The conserved N-terminus of zinc metalloprotease B was identified as eliciting strong early IgG responses.
• Despite a polyvalent antibody repertoire, continued pneumococcal carriage suggests mechanisms like mucosal immunity inhibition; however, higher IgG levels are associated with reduced pneumonia incidence and severity.