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

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.

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

“…This observation is in line with the previously reported polarization of aP-primed individuals towards Th2 responses (16) which are expected to correlate with increased IgE secretion, and which was also observed in aPprimed infants (14). Observing differences in antibody isotype polarization decades after the initial priming is interesting and was also observed at the level of T cell responses (18).…”

“…In all groups, male and female subjects were included equally and originally vaccinated with either DTwP or DTaP in infancy, received a booster vaccination with Tdap and donated blood, before the boost, 1, 3,7,14,30 Multiplexed Luminex Immunoassays. Antigen-specific antibody responses were measured through a modified multiplexed Luminex assay as previously reported (18,40). Pertussis, tetanus Immuno-Oncology, Immune Response and Metabolism allowed the identification of a total of 276 proteins and soluble factors in plasma.…”

“…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.…”

Development and Validation of a Bordetella pertussis Whole-Genome Screening Strategy

“…When immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines were compared, BP-specific memory CD4 + T cell responses were associated with Th1/Th17 versus Th2 differential polarization as a function of childhood vaccination [10]. Strikingly, after aP booster, donors originally primed with aP were associated with lower responses ex vivo and lower in vitro proliferation.…”

“…Several studies and epidemiological evidence suggest that the immunity induced by Bordetella pertussis (BP) acellular vaccines (aP) wanes more rapidly as compared to the immunity elicited by vaccines based on whole BP cells (wP) [1][2][3][4][5][6][7][8]. In previous studies [9,10], we have investigated potential immune correlates of this waning immunity, by dissecting immune responses in young adults, originally primed with either aP or wP vaccines. These studies were enabled by the definition of the T cell epitopes contained in the BP antigens contained in the aP vaccines (pertussis toxin, PtTox; two serotypes of fimbriae, Fim2/3; filamentous hemagglutinin, FHA; and pertactin, PRN), which was achieved following the systematic analysis of responses following the expansion of antigen-specific T cells in short-term in vitro culture [9], and the development of the activation-induced marker (AIM) assays, which allowed measurement of responses directly ex vivo without any further manipulation [11,12].…”