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Published on: April 13, 2017
Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters
Ricardo da Silva Antunes1, Mariana Babor1, Chelsea Carpenter1
1Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Insights
Childhood whole-cell pertussis (wP) vaccines prime T cells better than acellular pertussis (aP) vaccines. Adults initially primed with aP show weaker T cell memory responses to aP boosters compared to wP-primed individuals.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Whole-cell pertussis (wP) vaccines were replaced by acellular pertussis (aP) vaccines due to adverse events.
- Recent increases in pertussis disease highlight potential waning immunity with aP vaccines.
- Investigating long-term immune memory differences based on initial pertussis vaccine type is crucial.
Purpose of the Study:
- To compare T cell immune responses to acellular pertussis (aP) boosters in individuals initially primed with either whole-cell pertussis (wP) or aP vaccines.
- To analyze the polarization and proliferation capacity of pertussis-specific memory CD4+ T cells ex vivo.
- To understand the long-lasting immunological effects of childhood pertussis vaccination strategies.
Main Methods:
- Utilized activation-induced marker (AIM) assays to assess ex vivo T cell responses.
- Quantified cytokine production (e.g., IL-4, IFN-γ, IL-17) from CD4+ T cells after aP booster stimulation.
- Evaluated memory T cell expansion and in vitro proliferation capacity.
Main Results:
- Individuals initially primed with aP exhibited a Th2-biased response (increased IL-4, IL-5, IL-13, IL-9, TGF-β) and reduced Th1/Th17 responses (decreased IFN-γ, IL-17) after a contemporary aP booster.
- aP-primed individuals showed defective ex vivo memory cell expansion and reduced in vitro proliferation capacity compared to wP-primed individuals.
- Antibody titers and plasmablast numbers increased similarly in both groups, indicating T cell-specific differences.
Conclusions:
- Initial vaccination with aP leads to long-lasting differences in T cell polarization and proliferation compared to wP.
- These findings suggest that the type of initial pertussis vaccination impacts the quality and function of T cell memory.
- The study underscores the importance of considering initial priming in evaluating vaccine effectiveness and potential strategies to enhance T cell immunity.
Abstract:
In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4+ T cell responses ex vivo, highlighting a type 2/Th2 versus type 1/Th1 and Th17 differential polarization as a function of childhood vaccination. Remarkably, after a contemporary aP booster, cells from donors originally primed with aP were (a) associated with increased IL-4, IL-5, IL-13, IL-9, and TGF-β and decreased IFN-γ and IL-17 production, (b) defective in their ex vivo capacity to expand memory cells, and (c) less capable of proliferating in vitro. These differences appeared to be T cell specific, since equivalent increases of antibody titers and plasmablasts after aP boost were seen in both groups. In conclusion, our data suggest that there are long-lasting effects and differences in polarization and proliferation of T cell responses in adults originally vaccinated with aP compared with those that initially received wP, despite repeated acellular boosters.
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