An in vitro immune response model to determine tetanus toxoid antigen (vaccine) specific immunogenicity: Selection of sensitive assay criteria

Sytse J. Piersma, Marlies P.P.A.M. Leenaars, Laurence Guzylack-Piriou, Artur Summerfield, Coenraad F.M. Hendriksen, Ken C. McCullough

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Many vaccines employed in childhood vaccination programmes are produced by conventional techniques, resulting in complex biological mixtures for which batch-related quality control requires in vivo potency testing. Monitoring consistency via in vitro tests during the vaccine production has the capacity to replace certain of the in vivo methods. In this respect, determining vaccine antigen immunogenicity through functional immunological tests has high potential. Advances in immunology have made it possible to analyse this biological activity by in vitro means. The present study established such an in vitro test system for tetanus toxoid (TT). This measured vaccine immunogenicity through an antigen-specific secondary (recall) response in vitro, using a porcine model growing in value for its closeness to human immune response characteristics. Discrimination between the specific recall TT antigen and diphtheria toxoid (DT) was possible using both peripheral blood mononuclear cell cultures and monocyte-derived dendritic cells in co-culture with autologous specific lymphocytes. TT-specific activation was detected with highest discrimination capacity using proliferation assays, as well as IFN-gamma and TT-specific antibody ELISPOTS (measuring secreting T and B lymphocytes, respectively). These in vitro systems show a high potential for replacing animal experimentation to evaluate the immunogenicity of complex vaccines.

Original languageEnglish
Pages (from-to)3076-3083
Number of pages8
JournalVaccine
Volume24
Issue number16
DOIs
StatePublished - Apr 12 2006
Externally publishedYes

Keywords

  • In vitro antigen presentation
  • Tetanus toxoid
  • Vaccine quality control

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    Piersma, S. J., Leenaars, M. P. P. A. M., Guzylack-Piriou, L., Summerfield, A., Hendriksen, C. F. M., & McCullough, K. C. (2006). An in vitro immune response model to determine tetanus toxoid antigen (vaccine) specific immunogenicity: Selection of sensitive assay criteria. Vaccine, 24(16), 3076-3083. https://doi.org/10.1016/j.vaccine.2006.01.061