Whole-Cell or Acellular Pertussis Primary Immunizations in Infancy Determines Adolescent Cellular Immune Profiles

Abstract

IntroductionPertussis is re-emerging worldwide, despite effective immunization programs for infants and children. Epidemiological studies show a more limited duration of protection against clinical pertussis in adolescents primed with acellular pertussis (aP) vaccines during infancy than those who have been primed with whole-cell pertussis (wP) vaccines. This study aimed to determine whether memory immune responses to aP, diphtheria, and tetanus vaccine antigens following booster vaccinations at 4 and 9 years of age differ between wP- versus aP-primed children.MethodsIn a cross-sectional study, blood was collected of DTwP- or diphtheria, tetanus, and aP (DTaP)-primed children before, 1 month, and 2 years after the preschool DTaP booster administered at 4 years of age (n = 41–63 per time point). In a longitudinal study, blood was sampled of DTwP- or DTaP-primed children before, 1 month, and 1 year after a preadolescent Tdap booster at 9 years of age (n = 79–83 per time point). Pertussis, diphtheria, and tetanus vaccine antigen-specific IgG levels, B-cell and T-cell responses were determined.ResultsAfter the preschool booster vaccination, IgG levels were significantly higher in aP-primed as compared with wP-primed children until 6 years of age. Before the preadolescent Tdap booster vaccination, humoral and cellular immune responses were similar in aP- and wP-primed children. However, the Tdap booster vaccination induced lower vaccine antigen-specific humoral, B-cell, and T-helper 1 (Th1) cell responses resulting in significantly lower Th1/Th2 ratios in aP-primed compared with wP-primed children.ConclusionThe memory immune profiles at preadolescent age to all DTaP vaccine antigens are already determined by the wP or aP combination vaccines given in infancy, showing a beneficial Th1-dominated response after wP-priming. These immunological data corroborate epidemiological data showing that DTaP-primed adolescents are less protected against clinical pertussis than DTwP-primed children.

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

“…Notably, the differential Th polarization was maintained even in teenagers and adults. Since polarization is maintained for years after the original priming, even after identical boosting with aP (35,43), data support the notions that wP priming enacts a differential molecular program in the vaccine-specific T cells and that this imprinting is essentially lifelong.…”

“…Pertussis responses remain polarized as a function of the original priming vaccine (which correlates with another report, ref. 35), but not toward CMV/EBV. Polarization was associated with IL-4, IL-9, and TGF-β in aP-primed and IFN-γ and IL-17 in wP-primed donors.…”

“…Specifically, we measured IFN-γ, IL-4, and IL-17 responses in the 2 donor cohorts 1 to 3 months after aP boosting and calculated the number of total CD4 + T cells producing each cytokine. We responses, resulting in less effective and/or durable responses as immunological mechanisms to explain the decreasing efficacy of aP vaccination (32)(33)(34)(35).…”

Pertussis surveillance in a children hospital in Bangkok, Thailand

“…In developing countries such as Thailand, data on pertussis burden in children is lacking to support a maternal immunization policy regarding pertussis (Forsyth et al, 2012). A modeling study has demonstrated a long duration of pertussis immunity in Thai population (Blackwood et al, 2013), whereas as much as 18% of Thai adults with prolonged cough had documented pertussis in a serological study (Siriyakorn et al, 2016). Recommendation of pertussis vaccines for Thai pregnant women justifies more information apart from the country routine disease report, in which pertussis in infants could go underrecognized.…”

A system-view ofB. pertussisbooster vaccine responses in adults primed with whole-cell vs. acellular vaccine in infancy

“…Attempts, including from our own group, were undertaken to characterize and compare immunological response in DTwP and DTaP primed individuals in terms of humoral (4,(13)(14)(15) and T-cell mediated immunity (16)(17)(18)(19)(20). These studies showed that both wP and aP-primed individuals are capable of strong humoral response resulting in high levels of IgG against B. pertussis antigens.…”