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Poor memory B cell generation contributes to non-protective responses to DTaP vaccine antigens in otitis-prone
1Rochester General Hospital Research Institute, Rochester, NY, USA.
Insights
Children with recurrent ear infections (acute otitis media) have lower antibody and memory B cell responses to vaccines like DTaP. This immune deficiency may explain their increased susceptibility to infections.
Area of Science:
- Immunology
- Pediatrics
- Vaccinology
Background:
- Recurrent acute otitis media (AOM) in children is often linked to impaired immune responses.
- Previous studies identified children with recurrent AOM who do not develop protective antibody levels against common pathogens and vaccine antigens.
Purpose of the Study:
- To compare antibody levels and memory B cell responses to DTaP vaccine antigens in children with and without recurrent AOM.
- To investigate the relationship between memory B cell frequency and circulating antibody titers in these children.
Main Methods:
- Sera from 15 otitis-prone (sOP) and 20 non-otitis-prone (NOP) children were analyzed for IgG antibody concentrations against diphtheria toxoid (DT), tetanus toxoid (TT), and acellular pertussis toxoid (PT).
- Peripheral blood samples were used to quantify antigen-specific CD19(+) CD27(+) memory B cells using fluorescently conjugated vaccine antigens.
- Statistical analysis was performed to compare groups and assess correlations.
Main Results:
- sOP children exhibited significantly lower IgG antibody concentrations against DTaP vaccine antigens compared to NOP children.
- A significantly lower percentage of antigen-specific memory B cells was observed in sOP children.
- A positive linear correlation was found between memory B cell frequencies and IgG antibody titers for DT, TT, and PT.
Conclusions:
- Children with recurrent AOM demonstrate impaired adaptive immune responses to DTaP vaccination, characterized by reduced antibody production and memory B cell generation.
- These findings suggest a potential immunological basis for the susceptibility to infections in children with recurrent AOM.
- This study is the first to demonstrate differences in DTaP-specific memory B cell responses and their correlation with antibody levels in young children with recurrent AOM.
Abstract:
We recently identified a cohort of children with recurrent episodes of acute otitis media (AOM) who fail to generate protective antibody titres to otopathogens and several vaccine antigens. In this study we determined the antibody levels against DTaP vaccine antigens, diphtheria toxoid (DT), tetanus toxoid (TT) and acellular pertussis toxoid (PT) in sera from 15 stringently defined otitis-prone (sOP) children and 20 non-otitis-prone (NOP) children. We found significantly lower concentrations of immunoglobulin (Ig)G antibodies against vaccine antigens in the serum of sOP children compared to age-matched NOP children. To elucidate immunological cellular responses to the vaccines in these children, we investigated memory B cell responses to DTaP vaccination. We used fluorescently conjugated vaccine antigens to label antigen receptors on the surface of memory B cells and examined the frequency of antigen-specific CD19(+) CD27(+) memory B cells in the peripheral blood. sOP children showed a significantly lower percentage of antigen-specific CD19(+) CD27(+) memory B cells than NOP children. We also found a linear correlation between the frequencies of memory B cells and circulating IgG titres for DT, TT and PT proteins. To our knowledge, this is the first study to show significant differences in memory B cell responses to DTaP vaccine antigens and their correlation with the circulating antibodies in young children with recurrent AOM.
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