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Published on: February 22, 2019
Immunologic profiling of the infant immune response to whole-cell and acellular pertussis vaccines
C Buddy Creech1, Mariana Leguia2, Johannes B Goll3
1Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. buddy.creech@vumc.org.
Insights
Whole-cell pertussis vaccine (DTP) elicits stronger early immune responses than acellular pertussis vaccine (DTaP), indicated by TLR-signaling and phagocytosis pathways. DTP also resulted in more PT-specific B-cells after booster vaccination.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Immunity from acellular pertussis vaccine (DTaP) wanes, increasing pertussis risk.
- Whole-cell pertussis vaccine (DTP) may offer more durable protection, particularly when given as a first dose.
Purpose of the Study:
- To investigate the early immunologic responses to DTP versus DTaP in infants.
- To compare the molecular and cellular immune profiles following primary and booster vaccinations.
Main Methods:
- RNA-sequencing and ribosome profiling of peripheral blood mononuclear cells (PBMCs) from 56 infants.
- Analysis of immune responses at baseline, Day 2, and Day 8 post-vaccination, and after booster doses.
- Pathway enrichment analysis to identify differentially activated immune pathways.
Main Results:
- DTP recipients showed enriched TLR-signaling and FcϒR-mediated phagocytosis pathways on Days 2 and 8.
- DTP administration led to increased levels of IRAK-4 and IL-1ß compared to DTaP.
- A higher frequency of pertussis toxin (PT)-specific B-cells was observed in DTP recipients after booster vaccination.
Conclusions:
- DTP induces distinct and potentially more robust early immune responses compared to DTaP.
- Findings provide insights into the immunological basis for DTP's potentially longer-lasting protection.
- Results may inform the development of next-generation pertussis vaccines.
Abstract:
Despite robust antibody responses, immunity induced by acellular pertussis vaccine (DTaP) wanes over time and risk of pertussis seems to be lower in children who receive whole-cell vaccine (DTP) as their first dose. To interrogate the early immunologic response to pertussis vaccine, we enrolled 56 healthy infants who received either DTP or DTaP at 2-, 4-, 6-, and 18-months of age. RNA-sequencing and ribosome profiling of PBMC were performed prior to vaccination (Day 1) and on either Day 2 or Day 8. Pathway enrichment analysis on Days 2 and 8 showed enrichment of TLR-signaling and FcϒR-mediated phagocytosis among DTP recipients. DTP also led to increases in IRAK-4 and IL-1ß. After booster vaccination, a higher frequency of PT-specific B-cells was observed in DTP- vs. DTaP recipients. These data provide insights into the early immunologic responses to pertussis vaccine and may guide next-generation pertussis vaccine development.
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