Multiple discontinuity as a remarkable feature of the development of acellular pertussis vaccines

Development of the Japanese acellular pertussis vaccines (APVs) of the 1980s involved six procedural or conceptual features that were discontinuous with the then-accepted views of how pertussis vaccines should be made and tested. These discontinuities were: modification of the standard intracerebral mouse test for protective potency; use of culture supernates, rather than cells, of Bordetella pertussis as the feedstock for antigen purification; use of haemagglutination as a measure of protective antigen(s); identification of pertussis toxin (PT) as the main protective antigen; complete inactivation of the biological activities of PT by formalin; and the use of a single strain of B. pertussis. Several of these discontinuities had long precedence in the pertussis literature, but the original observations had not been incorporated into the mainstream of pertussis vaccinology and were therefore ‘premature’. The APVs, purified from culture-supernates, emerged after a long period of unsuccessful research on the split-cell pertussis vaccines, i.e. those derived from the bacterial cells themselves. There is a brief discussion of why APVs have taken so long to obtain acceptance outside Japan, and of how the listed discontinuities may be explicable in terms of antigen processing by the immune system. General lessons, applicable to vaccines for other infectious diseases, may be learned from this account of how APVs have evolved from whole-cell pertussis vaccines.