Th1 versus Th2 T cell polarization by whole-cell and acellular childhood pertussis vaccines persists upon re-immunization in adolescence and adulthood

Abstract

The recent increase in cases of whooping cough among teenagers in the US suggests that the acellular Bordetella pertussis vaccine (aP) that became standard in the mid 1990s might be relatively less effective than the whole-bacteria formulation (wP) previously used since the 1950s. To understand this effect, we compared antibody and T cell responses to a booster immunization in subjects who received either the wP or aP vaccine as their initial priming dose in childhood. Antibody responses in wP- and aP-primed donors were similar. Magnitude of T cell responses was higher in aP-primed individuals. Epitope mapping revealed the T cell immunodominance patterns were similar for both vaccines. Further comparison of the ratios of IFNγ and IL-5 revealed that IFNγ strongly dominates the T cell response in wP-primed donors, while IL-5 is dominant in aP primed individuals. Surprisingly, this differential pattern is maintained after booster vaccination, at times from eighteen years to several decades after the original aP/wP priming. These findings suggest that childhood aP versus wP vaccination induces functionally different T cell responses to pertussis that become fixed and are unchanged even upon boosting.

Keywords: Epitope; Pertussis; Re-immunization; T cell polarization; Vaccine.

Fig 1

Magnitude and immunodominance of antibody and T cell responses are similar between wP- and aP-primed cohorts. (A) Sum of titers across all aP antigens from each donor in wP/no boost and aP/no boost cohorts, as assayed by ELISA. (B) Immunodominance of antigens in both cohorts expressed as the percentage of the total response. (C) Overall responses against aP peptides as measured by dual color ELISPOT. Each data point represents the sum of responses across all aP antigens for a single wP/no boost or aP/no boost donor. (D) Immunodominance of each antigen is expressed as percentage of the total T cell response in wP and aP cohorts. Data is expressed as median ± interquartile range for each cohort. *: p < 0.05, ns, no significant difference by Mann-Whitney test.

Fig 2

aP boosting increases B cell responses in wP- and aP-primed donors. (A) Sum of antibody titers for all aP antigens with or without aP boost (0.5–3 months post boost). wP (circles) and aP (squares). (B) Immunodominance of antigens in both wP/aP and aP/aP cohorts expressed as the percentage of the total response. (C–F) Sum of antibody titers for individual aP antigens with or without aP boost (0.5–3 months post boost). wP (circles) and aP (squares). (C) FHA, (D) Fim2/3, (E) PRN and (F) PT. Data are expressed as median ± the interquartile range for each cohort. *: p<0.05, **: p<0.01, ***:p<0.001, ****:p<0.0001, ns: no significant difference by Mann-Whitney test.

Fig 3

aP boosting increases T cell responses in wP-primed donors. (A) Sum of T cell responses for all aP antigens with or without aP boost (0.5–3 months post boost). wP (circles) and aP (squares). (B) Immunodominance of antigens in both wP/aP and aP/aP cohorts expressed as the percentage of the total response. (C–F) Sum of T cell responses for individual aP antigens with or without aP boost (0.5–3 months post boost). wP (circles) and aP (squares). (C) FHA, (D) Fim2/3, (E) PRN and (F) PT. Data are expressed as median ± the interquartile range for each cohort. *: p<0.05, ns: no significant difference by Mann-Whitney test.

Fig 4

Similar epitope repertoires recognized by aP-primed and wP-primed individuals. (A) The proportion of each donor cohort who respond to the indicated number of epitopes, wP squares and aP circles. (B) Epitopes ranked on the basis of magnitude of response. wP; black line, aP; dashed line. Dotted lines indicate the top 50 and 100 epitopes. (C) Epitopes ranked on the basis of the response frequency for wP and aP combined. Black dotted line indicates the top 132 epitopes recognized by >5% of donors. (D) Overlap of top 132 epitopes recognized in 5 or more individuals in wP- and aP-primed cohorts.

Fig 5

Differential polarization of T cell responses. (A) The number of IL-5 and IFNγ SFCs were measured by dual color ELISPOT assays. Each data point represents the ratio of IFNγ/IL-5 SFCs from each donor; bars represent the median ± interquartile range. ****: p < 0.0001 by Mann-Whitney test. (B) Ratio of IFNγ to IL-5 secreting cells as a function of age. Each data point represents the log of the IFNγ/IL-5 SFC ratio from each donor. The best fit of each data set is represented by linear regression lines; R-squared and p values are shown.