Evaluation of immune responses to Tdap booster during pregnancy in women who received whole cell or acellular pertussis vaccines during childhood

Abstract

Pertussis, caused by Bordetella pertussis (Bp), results in severe morbidity and mortality in infants. Since 2012, the tetanus, diphtheria and pertussis (Tdap) booster vaccine is recommended during every pregnancy to protect infants who are too young to be immunized. While infants of whole cell pertussis vaccine (wPV)-primed pregnant individuals are well protected from severe disease, the effectiveness of this strategy has not been assessed in acellular pertussis vaccine (aPV)-primed pregnant women. Our primary objective was to compare the cellular and humoral immune responses following Tdap booster in pregnant participants who received the wPV or aPV as infants. As a secondary objective we compared responses of pregnant women to wPV- and aPV-primed non-pregnant controls. All pertussis and non-pertussis specific serum antibody levels increased post-Tdap booster in aPV- and wPV-primed groups. Antibody avidity was higher in wPV-primed pregnant participants compared to aPV-primed pregnant women before and after Tdap booster. In contrast, antibody opsonic activity remained unchanged in either priming group. Antibody secreting cells specific for all pertussis and non-pertussis antigens increased following booster immunization. Expression of early T cell activation markers OX-40, PD-L1 and CD25 and cytokines IFNγ, IL-17 and IL-4 showed that T cell function was unaffected by Tdap booster and maintained the phenotypes elicited by the childhood priming vaccine. Secondary analysis showed that antibody and T cell responses to Tdap booster were higher in nonpregnant control participants compared to pregnant women, suggesting that responses to Tdap booster were blunted in pregnancy.

Keywords: Pertussis; Tdap; cellular immunity; humoral immunity; maternal; vaccination.

Figure 1.

Overall study design. Female (18–45 years of age) participants immunized with aPV or wPV as children were enrolled. Both groups received the aPV booster. PBMCs and sera were isolated pre- (V1) and post- booster immunization (V2). Downstream analysis of humoral and cellular immune responses is shown. Schematic made in Biorender®.

Figure 2.

Serum antibody titres and avidity are lower in aPV primed compared to wPV primed pregnant participants. The (A) anti-PT, (B) anti-FHA, and (C) anti-PRN specific IgG antibodies in the sera of aPV (N = 15) or wPV primed (N = 44) pregnant patients pre- and post-booster immunization. Antibody avidity in the sera was also determined to (D) PT, (E) FHA, and (F) PRN at V1 and V2. Specific (G) Anti-DT and (H) anti-TT antibody levels pre- and post-booster immunization of both aPV and wPV primed pregnant women. Antibody avidity to (I) DT and (J) TT was determined before and after booster immunization. **P < 0.01, ***P < 0.001, and ****P < 0.0001 compared V1 to V2 for each antigen. ++P < 0.01, +++P < 0.001, ++++P < 0.0001 comparing V1 and V2 between different immunization groups.

Figure 3.

Bp opsonization is not increased following Tdap booster immunization during pregnancy in either aPV or wPV primed participants. (A) Protein A/G mag beads were incubated with sera of aPV-primed (N = 15) or wPV-primed (N = 58) pregnant patients before and after booster immunization. Following incubation, sera coated beads were incubated with Bp that was stained using Baclite green. (B) Green fluorescence was quantified and compared between V1 and V2 of each group, and between aPV and wPV primed participants. Schematic made in Biorender®.

Figure 4.

Booster immunization increased ASCs to pertussis and non-pertussis Tdap vaccine antigens. ELISpots quantification of the (A) PT, (B) FHA, (C) PRN, (D) DT and (E) TT before and after booster immunization of aPV (N = 10–11) and wPV (N = 11) primed pregnant women. *P < 0.05, **P < 0.01, and ***P < 0.001.

Figure 5.

Booster immunization increased AIM + cells in aPV- and wPV-primed pregnant women. The percentage of (A) OX40+ CD25 + and (B) PDL1 + CD25+ CD4+ T cells in peripheral blood of both aPV-primed (N = 13) and wPV-primed (N = 56) pregnant participants at V1 compared to V2 for each priming group were determined by flow cytometry. *P < 0.05, **P < 0.01, and ***P < 0.001.

Figure 6.

Cytokine production by peripheral blood CD4+ T cells is unchanged by Tdap booster during pregnancy. The percentage of (A) IFNɣ, (B) IL-4, and (C) IL-17 producing cells were evaluated pre- and post-booster immunization of aPV (N = 10) and wPV (N = 10) primed pregnant participants by intracellular cytokine staining and quantified by flow cytometry. *P < 0.05, and ***P < 0.001.

Figure 7.

wPV immunized nonpregnant participants have increased anti-PT IgG serum antibody titres following Tdap booster compared to aPV immunized participants. The (A) anti-PT, (B) anti-FHA, (C) anti-PRN, anti-DT (D) and anti-TT (E) specific IgG antibodies in the sera of aPV or wPV nonpregnant participants following Tdap booster immunization was quantified by ELISA (N = 15–25). **P < 0.01, ***P < 0.001, ****P < 0.0001.