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Published on: August 7, 2017
Infants with low vaccine antibody responses have altered innate cytokine response
Naveen Surendran1, Ted Nicolosi1, Michael Pichichero2
1Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester Regional Health System, 1425 Portland Ave, Rochester, NY, United States.
Insights
Ten percent of infants are low vaccine responders (LVRs), exhibiting reduced antibody levels post-vaccination. LVR infants show distinct immune cell responses to TLR7/8 agonist R848 stimulation compared to normal responders.
Area of Science:
- Immunology
- Pediatrics
- Vaccinology
Background:
- A subset of infants (10%) demonstrates sub-protective antibody levels following routine pediatric vaccinations.
- These infants, termed low vaccine responders (LVRs), exhibit dysregulated innate and adaptive immune responses.
- Understanding the immunological basis of LVR is crucial for improving vaccine efficacy in this population.
Purpose of the Study:
- To investigate the immune cell response differences between LVR infants and normal vaccine responders (NVRs).
- To analyze the cytokine and chemokine profiles following stimulation with a Toll-like receptor 7/8 (TLR7/8) agonist.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were isolated from LVR and NVR infants.
- PBMCs were stimulated with the TLR7/8 agonist R848.
- Cytokine levels (IFN-α, IL-12p70, IL-1β) and chemokine levels (CCL5/RANTES) were measured.
Main Results:
- LVR infants exhibited significantly lower levels of IFN-α, IL-12p70, and IL-1β upon R848 stimulation compared to NVR infants.
- Conversely, LVR infants showed higher levels of CCL5 (RANTES) production.
- These findings indicate a distinct cytokine and chemokine profile associated with low vaccine responsiveness.
Conclusions:
- LVR infants display an altered immune response characterized by reduced pro-inflammatory cytokines and increased CCL5 production.
- These immune differences may contribute to the sub-protective antibody levels observed in LVR infants.
- Further research into modulating these immune responses could enhance vaccine efficacy in LVR infants.
Abstract:
We recently identified a population of 10% of infants who respond with sub-protective antibody levels to most routine primary pediatric vaccinations due to altered innate and adaptive immune responses. We term these infants as low vaccine responders (LVRs). Here we report new data showing that TLR7/8 agonist - R848 stimulation of PBMCs of LVR infants elicit significantly lower IFN-α, IL-12p70 and IL-1β, while inducing higher levels of CCL5 (RANTES) compared to normal vaccine responder (NVR) infants.
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