Pertussis-specific memory B-cell and humoral IgG responses in adolescents after a fifth consecutive dose of acellular pertussis vaccine

Abstract

In order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in Sweden in 2016. Preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. Reported here are the memory B-cell and serological responses detected in a smaller cohort (n = 34) of the 230 subjects recruited to the study. All subjects had received primary vaccination consisting of three doses of diphtheria-tetanus-5-component pertussis (DTaP5) vaccine, at 3, 5, and 12 months of age, and a tetanus-low-dose diphtheria-5-component pertussis (Tdap5) vaccine booster at 5.5 years. In this study, the subjects were randomly assigned and received either a Tdap1 or Tdap5 booster. Of the 230 participants, 34 subjects had samples available for evaluation of IgG-producing memory B-cell responses. Both vaccine groups had significant increases in pertussis toxin-specific serum IgG levels, but only the 1-component group showed significant increases in pertussis toxin-specific memory B cells. The 5-component group had significant increases in filamentous hemagglutinin- and pertactin-specific memory B-cell and serum IgG levels; these were not seen in the 1-component group, as expected. In conclusion, this study shows that a 5th consecutive dose of an acellular pertussis vaccine induces B-cell responses in vaccinated adolescents. (This study has been registered at EudraCT under registration no. 2008-008195-13 and at ClinicalTrials.gov under registration no. NCT00870350.).

FIG 1

Flow chart of the subjects included in the antigen-specific memory B-cell ELISpot analysis.

FIG 2

Pertussis-specific IgG-producing memory B-cell responses after a fifth dose of acellular pertussis vaccines. (A) A significant increase (P < 0.05, indicated by asterisks) in PT-specific memory B cells was detected in the 1-component group, with 11 of 16 subjects responding to the vaccination. No significant increase could be detected in the 5-component group. (B) FHA-specific memory B cells were significantly increased (P < 0.05) postvaccination in the 5-component group, with 5 of 8 subjects responding to the vaccination. No response was seen for the 1-component group. (C) Similar results were found for PRN-specific responses, with a significant increase (P < 0.05) in the 5-component group, in which 10 of 11 subjects responded. No response was detected in the 1-component group. Bars, median values; dotted lines, cutoff levels for positive vaccine responders.

FIG 3

Serological pertussis-specific IgG responses after a fifth dose of acellular pertussis vaccines. (A) Significant increases (P < 0.05, indicated by asterisks) in PT-specific serum IgG levels were detected in both groups, albeit at higher levels in the 1-component group than in the 5-component group. All 16 subjects in the 1-component group and 14 of 15 subjects in the 5-component group responded. (B and C) The 5-component group had significant increases (P < 0.05) in the responses to FHA (B) and PRN (C), with 15 of 15 subjects responding to both antigens. The 1-component group did not mount any serological responses to FHA or PRN. Bars, median values; dotted lines, cutoff levels for positive vaccine responders.

FIG 4

Subjects with high prevaccination serum IgG levels. High pertussis-specific serum IgG levels were detected in three of the subjects. All subjects had high antibody levels against all antigens tested, except for one subject who did not have high PT-specific serum levels prevaccination but did respond to that antigen following booster vaccination. The high prevaccination levels were not detected in the peripheral memory B-cell responses. All three subjects responded with PT-specific memory B cells, whereas the only subject with samples available for assessment of FHA and PRN responses showed decreased levels postvaccination versus prevaccination. Dotted lines, cutoff levels for positive vaccine responders.

FIG 5

Correlation between antigen-specific humoral and memory B-cell responses in the 1-component group. A significant correlation between the IgG-specific humoral and memory B-cell responses was detected only for the pertussis toxin-specific responses in the 1-component group (Spearman r = 0.638, P = 0.001). The x axis was segmented for better view of the data for individual subjects.