COLLABORATIVE STUDY ON TEST SYSTEMS TO ASSESS TOXICITY OF WHOLE-CELL PERTUSSIS-VACCINE

A collaborative study has been carried out to establish the precision and accuracy oi live test systems for the assessment oi the toxicity o i whole cell pertussis vaccine, To this end, six vaccines, including b oth ''normal'' and ''abnormal'' products with respect to arbitrary lev els of Pertussis toxin and/or potency were tested. The study included in vivo test systems as the Mouse Weight Gain (MWG) test; the current WHO- recommended bioassay to evaluate overall pertussis toxicity and f our specific test systems; the leukocytosis Promotion (LP) test, the H istamine Sensitization (HS) test and in vitro the Chinese Hamster Ovar y (CHO) clustering test to estimate pertussis toxin (PT) levels, and t he Limulus Amoebocyte Lysate (LAL) test to evaluate endotoxin levels. in addition, participants were also asked to estimate potency by the M ouse Protection test according to Kendrick (MP), Fourteen laboratories in various countries participated in the study. In almost all partici pating laboratories, the MWG test was not very accurate in evaluating the overall toxicity of whole cell pertussis vaccines. In addition, st atistical significant interlaboratory variation was frequently seen. T i-ie specific toxicity tests (LP, HS, CHO and LAL test) appeared to be more accurate, but large interlaboratory variation was seen, statisti cally significant at P <0.05 for LP test, CHO test and LAL test. Signi ficant variation in test results also occurred in the potency test. Fu rthermore, the discriminative power of the MP test between different l evels of potency was low. It was concluded that, on the condition of o ptimization and stringent standardisation, HS and CHO test and in part icular LP test might be more appropriate to assess PT activity than th e MWG test provided that the tests are optimised and stringently stand ardized. An inhibition ELISA was used to estimate levels of PT. This t est could be of value for prescreening purposes. The LAL test should b e used to estimate endotoxin activity. The value of the MP test, as a model to assess potency, is disputed. (C) 1997 The International Assoc iation of Biological Standardization.