TY - JOUR
T1 - An in vitro immune response model to determine tetanus toxoid antigen (vaccine) specific immunogenicity
T2 - Selection of sensitive assay criteria
AU - Piersma, Sytse J.
AU - Leenaars, Marlies P.P.A.M.
AU - Guzylack-Piriou, Laurence
AU - Summerfield, Artur
AU - Hendriksen, Coenraad F.M.
AU - McCullough, Ken C.
N1 - Funding Information:
The authors wish to thank Valérie Tâche for assistance with the lymphocyte and MoDC cultures, Heidi Gerber for preparation of the Mabs, and Daniel Brechbühl for vaccination and bleeding of the animals. This project was supported by the Netherlands Organisation for Health Research and Development (ZonMw; Project 3170.0060).
PY - 2006/4/12
Y1 - 2006/4/12
N2 - 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.
AB - 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.
KW - In vitro antigen presentation
KW - Tetanus toxoid
KW - Vaccine quality control
UR - http://www.scopus.com/inward/record.url?scp=33645046365&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2006.01.061
DO - 10.1016/j.vaccine.2006.01.061
M3 - Article
C2 - 16504349
AN - SCOPUS:33645046365
VL - 24
SP - 3076
EP - 3083
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 16
ER -