Variability of Vaccine Responsiveness in Young Children
Michael E Pichichero1, Lei Xu1, Eduardo Gonzalez1
1Center for Infectious Diseases and Immunology, Research Institute, Rochester General Hospital, Rochester, NewYork.
Insights
Early life cytokine biosignatures predict vaccine responsiveness in children. Low vaccine responders (LVRs) show impaired T-cell memory and antigen-presenting cell function, with antibiotic exposure linked to LVR.
Area of Science:
- Pediatric Immunology
- Vaccinology
- Infectious Disease Epidemiology
Background:
- Variability in vaccine responsiveness in young children is not well understood.
- Identifying early predictors of vaccine response is crucial for public health.
Purpose of the Study:
- To identify early life biosignatures predicting vaccine responsiveness in infants.
- To investigate the relationship between antibiotic exposure and vaccine responsiveness.
- To characterize immune memory and antigen-presenting cell (APC) function in children with varying vaccine responses.
Main Methods:
- Nasopharyngeal secretions collected in early infancy (1-3 weeks) for cytokine/chemokine analysis.
- Blood samples collected at 1 year to assess vaccine responsiveness (low, normal, high) and immune memory.
- Evaluation of antigen-presenting cell (APC) function in vitro.
Main Results:
- Specific cytokine/chemokine profiles in early infancy predicted low vaccine responder (LVR) status.
- Antibiotic exposure correlated with an increased incidence of LVR.
- LVR children exhibited reduced CD4+ T-helper memory cell responses and suboptimal APC function.
Conclusions:
- Early life cytokine biosignatures can predict a child's vaccine responsiveness.
- Antibiotic use in infancy is associated with impaired vaccine responsiveness.
- Low vaccine responsiveness is characterized by deficiencies in T-cell memory induction and APC function.
Background:
Variability in vaccine responsiveness among young children is poorly understood.
Methods:
Nasopharyngeal secretions were collected in the first weeks of life for measurement of cytokines/chemokines seeking a biomarker, and blood samples were collected at age 1 year to identify vaccine responsiveness status, defined as low vaccine responder (LVR), normal vaccine responder (NVR), and high vaccine responder (HVR), to test for vaccine antigen-induced immune memory and for antigen-presenting cell (APC) function.
Results:
Significantly lower specific cytokine/chemokine levels as biosignatures, measurable in nasopharyngeal secretions at infant age 1-3 weeks, predicted LVR status compared to NVR and HVR children. Antibiotic exposures were correlated with increased occurrence of LVR. At age 1 year, LVRs had fewer CD4+ T-helper 1 and T-helper 2 memory cells responsive to specific vaccine antigens. APC responses observed among LVRs, both at rest and in response to Toll-like receptor 7/8 stimulation by R848, were suboptimal, suggesting that altered innate immunity may contribute to immune deficiency in LVRs.
Conclusions:
Cytokine biosignatures in the first weeks of life may predict vaccine responsiveness in children during the first year of life. Antibiotic exposure is associated with LVR in children. CD4+ T-cell memory induction and APC deficiencies occur in LVR children.
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