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Detection of Polyfunctional T Cells in Children Vaccinated with Japanese Encephalitis Vaccine via the Flow Cytometry Technique
Published on: September 23, 2022
Prospective study of the innate cellular immune response in low vaccine responder children
Naveen Surendran1, Ted Nicolosi1, Ravinder Kaur1
1Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester Regional Health System, 1425 Portland Ave, Rochester, NY, USA.
Insights
Low vaccine responders (LVR) in infants show temporary innate immune deficiencies, particularly in antigen-presenting cells (APC). These deficiencies resolve by 12-15 months, suggesting delayed immune system maturation in LVR infants.
Area of Science:
- Immunology
- Pediatrics
- Vaccinology
Background:
- A previous study identified 10% of infants as low vaccine responders (LVR) after primary vaccination.
- LVR infants exhibited cellular deficiencies, including low memory B cells and suboptimal T cell and antigen-presenting cell (APC) responses.
- These LVR infants eventually achieved normal vaccine responses by booster doses.
Purpose of the Study:
- To investigate the ontogeny of innate immune responses in LVR children.
- To determine if the primary immune defect in LVR children lies within their innate immunity.
- To analyze innate immune responses between 6 and 36 months of age in LVR and normal vaccine responders.
Main Methods:
- Longitudinal, prospective study design.
- Analysis of innate immune responses in infants aged 6-36 months.
- Assessment of antigen-presenting cell (APC) function, including MHC II expression and cytokine production (IFN-α, IL-12p70, IL-1β) following stimulation.
Main Results:
- Suboptimal APC response in LVR children at 6-9 months included low basal MHC II expression and reduced R848 induced IRF7 fold change.
- LVR infants showed significantly lower levels of IFN-α, IL-12p70, and IL-1β at 6-9 months.
- By 12-15 months, the APC responses in LVR children reached parity with normal vaccine responders.
Conclusions:
- The suboptimal innate immune response in LVR infants may stem from a delayed maturation of the immune system.
- Innate immunity plays a crucial role in instructing adaptive immunity, as evidenced by the transient deficiencies in LVR infants.
- Further research into infant innate immunity is warranted due to its critical role in vaccine response and overall immune development.
Abstract:
We recently reported our findings from a longitudinal, prospective study where we identified 10% infants who were low vaccine responders (LVR) at age 9-12 mo following routine primary series vaccine schedule. We found multiple cellular deficiencies in LVR children, including low number of memory B cells, reduced polyclonal stimulation of naïve/memory T cell response and suboptimal APC response. These children outgrew their poor vaccine response by the time they received booster doses of vaccine. Studies in human infant innate immunity are rare because of the unique challenges in specimen collection. As innate immunity instructs adaptive immunity, we hypothesized that the primary immune defect lies with innate immunity and in this study we sought to determine the ontogeny of innate immune response in LVR children between 6 and 36 mo of age. Interestingly, suboptimal APC response observed in LVR children at 6-9 mo of age characterized by significantly ( P < 0.05) low basal MHC II expression, low R848 induced IRF7 fold change, as well as low IFN-α, IL-12p70 and IL-1β levels, came to parity with normal vaccine responders by 12-15 mo of age, suggesting that the observed immune deficiency in LVR children may be the result of delayed maturation of immune system.
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