Improving the cellular pertussis vaccine: Increased potency and consistency

Thalen, Marcel; Ark, Arno van der; IJssel, Jan van den; Straaten, Ineke van; Jansen, Dennis W.; Beuvery, Coen; Martens, Dirk E.; Tramper, J.

doi:10.1016/j.vaccine.2007.11.047

Cited by 22 publications

(12 citation statements)

References 15 publications

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“…The Dutch wP vaccine contained very small amounts of inactivated PT (29), which is in line with the weak antibody response to PT (7). Interestingly, however, the various recent peaks in pertussis disease in aP-vaccinated populations of Europe, the United States, and Australia indicate that priming with an aP vaccine in the first year of life induces a shorter immune protection later in childhood than priming with a wP vaccine (30)(31)(32)(33).…”

Section: Stimulated Cd8mentioning

confidence: 85%

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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Section: Stimulated Cd8mentioning

confidence: 85%

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

Rond

Schure

Öztürk

et al. 2015

Clin. Vaccine Immunol.

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“…The bioreactor cultivation method used for this work, with chemically defined growth medium (Thalen et al, 1999(Thalen et al, , 2006) and other previously described improvements Thalen et al, 2008), resulted in a highly reproducible process in terms of gene-expression, bacterial growth, and consumption of nutrients (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Gene‐expression‐based quality scores indicate optimal harvest point in Bordetella pertussis cultivation for vaccine production

Waterbeemd

Streefland

Pennings

et al. 2009

Biotech & Bioengineering

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The evolution of vaccine product quality during batch cultivation of Bordetella pertussis, the causative agent of whooping cough, was investigated with the goal to determine the optimal harvest point. The process was explored by measuring mRNA expression at frequent intervals during cultivation. The genes that are involved in virulence are already known for this product and changes in their expression levels are proposed to be indicative for product quality. A quantitative product quality score is calculated based on the expression levels of these virulence genes, which allows comparison of expected product quality between culture samples. Product quality scores were maximal throughout the logarithmic growth phase, but dropped significantly at the start of the stationary phase. This showed that the decreasing lactate and glutamate concentrations towards the end of the batch are critical for product quality. On-line measurement of these nutrients allows the cultivation process to be harvested at the optimal harvest point, increasing process robustness and consistency.

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“…These vaccines contain different amounts of pertussis antigens (48,51) but equal amounts of Dtx and TT. Both vaccines contain aluminum hydroxide as an adjuvant.…”

Section: Methodsmentioning

confidence: 99%

Fast, Antigen-Saving Multiplex Immunoassay To Determine Levels and Avidity of Mouse Serum Antibodies to Pertussis, Diphtheria, and Tetanus Antigens

Stenger¹,

Smits²,

Kuipers³

et al. 2011

Clin. Vaccine Immunol.

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To enhance preclinical evaluation of serological immune responses to the individual diphtheria, tetanus, and pertussis (DTP) components of DTP combination vaccines, a fast hexavalent bead-based method was developed. This multiplex immunoassay (MIA) can simultaneously determine levels of specific mouse serum IgG antibodies to P antigens P.69 pertactin (P.69 Prn), filamentous hemagglutinin (FHA), pertussis toxin (Ptx), and combined fimbria type 2 and 3 antigens (Fim2/3) and to diphtheria toxin (Dtx) and tetanus toxin (TT) in a single well. The mouse DTP MIA was shown to be specific and sensitive and to correlate with the six single in-house enzyme-linked immunosorbent assays (ELISAs) for all antigens. Moreover, the MIA was expanded to include avidity measurements of DTP antigens in a multivalent manner. The sensitivities of the mouse DTP avidity MIA per antigen were comparable to those of the six individual in-house avidity ELISAs, and good correlations between IgG concentrations obtained by both methods for all antigens tested were shown. The regular and avidity mouse DTP MIAs were reproducible, with good intra-and interassay coefficients of variability (CV) for all antigens. Finally, the usefulness of the assay was demonstrated in a longitudinal study of the development and avidity maturation of specific IgG antibodies in mice having received different DTP vaccines. We conclude that the hexaplex mouse DTP MIA is a specific, sensitive, and high-throughput alternative for ELISA to investigate the quantity and quality of serological responses to DTP antigens in preclinical vaccine studies.

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Improving the cellular pertussis vaccine: Increased potency and consistency

Cited by 22 publications

References 15 publications

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

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

Gene‐expression‐based quality scores indicate optimal harvest point in Bordetella pertussis cultivation for vaccine production

Fast, Antigen-Saving Multiplex Immunoassay To Determine Levels and Avidity of Mouse Serum Antibodies to Pertussis, Diphtheria, and Tetanus Antigens

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