Identification of pertussis-specific effector memory T cells in preschool children

Area of Science:

• Immunology
• Vaccinology
• Cellular Immunity

Background:

• Pertussis (whooping cough) remains a global health concern with evident resurgence despite vaccination efforts.
• Cellular immunity, particularly T-cell responses, is crucial for long-term protection against pertussis.
• Existing infant pertussis vaccines include whole-cell (wP) and acellular (aP) formulations, with differing impacts on immune memory.

Purpose of the Study:

• To compare pertussis-specific T-cell memory responses in children primed with either wP or aP vaccines.
• To evaluate the impact of the preschool acellular pertussis (aP) booster dose at 4 years of age on T-cell memory.
• To assess the persistence and quality of T-cell memory induced by different infant vaccination schedules.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) were isolated from children around 4 years of age, before and after an aP booster.
• PBMCs were stimulated with pertussis antigens, and T-cell responses were analyzed using flow cytometry for proliferation (CFSE dilution) and immune markers (CD4, CD3, CD45RA, CCR7, IFN-γ, TNF-α).
• Specific focus on CD4(+) and CD8(+) T-cell fractions, effector memory cells, and Th1 cytokine production.

Main Results:

• Pre-booster, aP-primed children had significantly higher proliferated pertussis toxin (PT)-specific CD4(+) and CD8(+) T-cell fractions compared to wP-primed children.
• Post-booster, aP-primed children showed enhanced induction of pertussis-specific CD4(+) effector memory cells (CD45RA(-) CCR7(-)) compared to wP-primed children.
• Infant aP vaccination induced persistent pertussis-specific CD4(+) and CD8(+) effector memory T-cell responses lasting until 4 years of age, surpassing wP-primed responses.

Conclusions:

• Infant acellular pertussis (aP) vaccination elicits superior and more persistent pertussis-specific T-cell memory responses compared to whole-cell (wP) vaccination.
• The preschool aP booster at 4 years of age did not significantly enhance T-cell memory subsets or functionality in either aP- or wP-primed children.
• The findings question the necessity of the current 4-year aP booster, suggesting a potential postponement to 6 years of age to optimize pertussis immunity.