PMID- 12678224
OWN - NLM
STAT- MEDLINE
DA  - 20030407
DCOM- 20030703
LR  - 20041117
IS  - 1424-6074 (Print)
IS  - 1424-6074 (Linking)
VI  - 111
DP  - 2002
TI  - Toxicity and immunogenicity of pertussis whole cell vaccine in one animal model.
PG  - 47-55
AB  - The required in vivo assays for the release of Whole Cell Pertussis Vaccine are
      the Mouse Weight Gain test (MWGT) for assessment of specific toxicity and the
      Mouse Protection test (MPT) to estimate the potency. Despite the fact that both
      assays are criticised for the use of large number of animals, poor precision or
      insensitivity, more precise alternatives--such as the Leukocytosis Promotion test
      (LP-test) and Pertussis Serological Potency Test (PSPT)--are still not fully
      accepted. During the optimisation of the production process, the need for more
      accurate parameters to determine toxicity and potency became essential. To reduce
      substantially the number of animals, we have combined the MWGT with the LP-test
      and PSPT in one model, named the Mouse Toxicity and Immunogenicity test
      (MTI-test). Animals are inoculated with half a human dose and are weighed
      individually pre-immunisation and 16 hours (parameter for endotoxin), three and
      seven days post immunisation. Additionally, the number of leukocytes (parameter
      for PT) is determined on day 7 and after 28 days the animals are bled
      individually for immunogenicity testing (parameter for potency). A lyophilised
      reference vaccine is included as a positive control to standardise the assay and 
      to determine its reproducibility. The advantage of this modified procedure is
      that the data on toxicity and immunogenicity are obtained from the individual
      mouse, which enables statistical analysis to be made. The leucocytosis data can
      be used to check whether mice were vaccinated correctly, allowing for the
      elimination of incorrectly vaccinated mice from the assay. Furthermore, this
      assay can be used to determine the consistency of production, the influence of
      adjuvant on toxicity, as well as the composition and stability of vaccines.
AD  - Laboratory of Control of Biological Products, RIVM, Bilthoven, The Netherlands.
FAU - van Straaten, I
AU  - van Straaten I
FAU - Levels, L
AU  - Levels L
FAU - van der Ark, A
AU  - van der Ark A
FAU - Thalen, M
AU  - Thalen M
FAU - Hendriksen, C
AU  - Hendriksen C
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Dev Biol (Basel)
JT  - Developments in biologicals
JID - 100940058
RN  - 0 (Antibodies)
RN  - 0 (Diphtheria-Tetanus-Pertussis Vaccine)
RN  - EC 2.4.2.31 (Pertussis Toxin)
SB  - IM
MH  - Animals
MH  - Antibodies/immunology/metabolism
MH  - Body Weight
MH  - Diphtheria-Tetanus-Pertussis Vaccine/*immunology/*toxicity
MH  - Female
MH  - Humans
MH  - Leukocytes/immunology/metabolism
MH  - Male
MH  - Mice
MH  - *Models, Animal
MH  - Organ Size
MH  - Pertussis Toxin/immunology/metabolism
MH  - Spleen/anatomy & histology
EDAT- 2003/04/08 05:00
MHDA- 2003/07/04 05:00
CRDT- 2003/04/08 05:00
PST - ppublish
SO  - Dev Biol (Basel). 2002;111:47-55.