Pertussis Circulation Has Increased T-Cell Immunity during Childhood More than a Second Acellular Booster Vaccination in Dutch Children 9 Years of Age

Schure, Rose-Minke; Rond, Lia de; Öztürk, Kemal; Hendrikx, Lotte H.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne‐Marie

doi:10.1371/journal.pone.0041928

Cited by 26 publications

(21 citation statements)

References 31 publications

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“…We have indications that booster responses induced by vaccination in combination with natural boosting with pertussis have resulted in increased T-cell responses in wP-primed children 6 and 9 years of age (39,40). In that study, however, the numbers of possible undiagnosed cases on the basis of elevated PT antibody levels were similar for wP-primed and aP-primed children.…”

Section: Discussionmentioning

confidence: 83%

Differential T- and B-Cell Responses to Pertussis in Acellular Vaccine-Primed versus Whole-Cell Vaccine-Primed Children 2 Years after Preschool Acellular Booster Vaccination

Schure

Hendrikx

Rond

et al. 2013

Clin Vaccine Immunol

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cThis study investigated long-term cellular and humoral immunity against pertussis after booster vaccination of 4-year-old children who had been vaccinated at 2, 3, 4, and 11 months of age with either whole-cell pertussis (wP) or acellular pertussis (aP) vaccine. Immune responses were evaluated until 2 years after the preschool booster aP vaccination. In a cross-sectional study (registered trial no. ISRCTN65428640), blood samples were taken from wP-and aP-primed children prebooster and 1 month and 2 years postbooster. Pertussis vaccine antigen-specific IgG levels, antibody avidities, and IgG subclasses, as well as T-cell cytokine levels, were measured by fluorescent bead-based multiplex immunoassays. The numbers of pertussis-specific memory B cells and gamma interferon (IFN-␥)-producing T cells were quantified by enzyme-linked immunosorbent spot assays. Even 2 years after booster vaccination, memory B cells were still present and higher levels of pertussis-specific antibodies than prebooster were found in aP-primed children and, to a lesser degree, also in wP-primed children. The antibodies consisted mainly of the IgG1 subclass but also showed an increased IgG4 portion, primarily in the aP-primed children. The antibody avidity indices for pertussis toxin and pertactin in aP-primed children were already high prebooster and remained stable at 2 years, whereas those in wP-primed children increased. All measured prebooster T-cell responses in aP-primed children were already high and remained at similar levels or even decreased during the 2 years after booster vaccination, whereas those in wP-primed children increased. Since the Dutch wP vaccine has been replaced by aP vaccines, the induction of B-cell and T-cell memory immune responses has been enhanced, but antibody levels still wane after five aP vaccinations. Based on these long-term immune responses, the Dutch pertussis vaccination schedule can be optimized, and we discuss here several options.

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Section: Discussionmentioning

confidence: 83%

Differential T- and B-Cell Responses to Pertussis in Acellular Vaccine-Primed versus Whole-Cell Vaccine-Primed Children 2 Years after Preschool Acellular Booster Vaccination

Schure

Hendrikx

Rond

et al. 2013

Clin Vaccine Immunol

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“…However, a previous study from the same group found Th1 and Th2 but no significant Th17 responses in C3H/HeJ and C3H/HeN mouse strains vaccinated with an aP containing PT and FHA (41). Nevertheless, data from two clinical studies recently showed negligible Th17 recall responses (∼10 pg/mL) in PBMC isolated from aP-vaccinated 4-y-old children before and after booster, suggesting aP does not induce Th17 memory in humans (43,44). Taken as a whole, the data presented in this study suggest that antibodies induced by aP vaccination are sufficient for preventing severe pertussis symptoms but do not mitigate colonization.…”

Section: Discussionmentioning

confidence: 96%

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Warfel

Zimmerman

Merkel

2013

Proc. Natl. Acad. Sci. U.S.A.

522

531

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Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.whooping cough | T-cell memory | animal models | adaptive immunity |

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“…We earlier have demonstrated that wP-primed children 9 years of age showed higher numbers of pertussis-specific T EM than wP-primed children 4 years of age due to the preschool booster vaccination in combination with the high circulation of pertussis (25). So, specific T cells are able to differentiate further upon pertussis vaccination and infection.…”

Section: Stimulated Cd8mentioning

confidence: 97%

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

Rond

Schure

Öztürk

et al. 2015

Clin. Vaccine Immunol.

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dWhooping cough remains a problem despite vaccination, and worldwide resurgence of pertussis is evident. Since cellular immunity plays a role in long-term protection against pertussis, we studied pertussis-specific T-cell responses. Around the time of the preschool acellular pertussis (aP) booster dose at 4 years of age, T-cell memory responses were compared in children who were primed during infancy with either a whole-cell pertussis (wP) or an aP vaccine. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with pertussis vaccine antigens for 5 days. T cells were characterized by flow-based analysis of carboxyfluorescein succinimidyl ester (CFSE) dilution and CD4, CD3, CD45RA, CCR7, gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣) expression. Before the aP preschool booster vaccination, both the proliferated pertussis toxin (PT)-specific CD4؉ and CD8 ؉ T-cell fractions (CFSE dim ) were higher in aP-than in wP-primed children. Post-booster vaccination, more pertussis-specific CD4؉ effector memory cells (CD45RA ؊ CCR7 ؊ ) were induced in aP-primed children than in those primed with wP. The booster vaccination did not appear to significantly affect the T-cell memory subsets and functionality in aP-primed or wP-primed children. Although the percentages of Th1 cytokine-producing cells were alike in aP-and wP-primed children pre-booster vaccination, aP-primed children produced more Th1 cytokines due to higher numbers of proliferated pertussis-specific effector memory cells. At present, infant vaccinations with four aP vaccines in the first year of life result in pertussis-specific CD4 ؉ and CD8 ؉ effector memory T-cell responses that persist in children until 4 years of age and are higher than those in wP-primed children. The booster at 4 years of age is therefore questionable; this may be postponed to 6 years of age.

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Pertussis Circulation Has Increased T-Cell Immunity during Childhood More than a Second Acellular Booster Vaccination in Dutch Children 9 Years of Age

Cited by 26 publications

References 31 publications

Differential T- and B-Cell Responses to Pertussis in Acellular Vaccine-Primed versus Whole-Cell Vaccine-Primed Children 2 Years after Preschool Acellular Booster Vaccination

Differential T- and B-Cell Responses to Pertussis in Acellular Vaccine-Primed versus Whole-Cell Vaccine-Primed Children 2 Years after Preschool Acellular Booster Vaccination

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Identification of Pertussis-Specific Effector Memory T Cells in Preschool Children

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