EFFECT OF SCHEDULE ON REACTOGENICITY AND ANTIBODY PERSISTENCE OF ACELLULAR AND WHOLE-CELL PERTUSSIS VACCINES - VALUE OF LABORATORY TESTS ASPREDICTORS OF CLINICAL-PERFORMANCE

The performance of four acellular pertussis vaccines containing betwee n two and five pertussis antigens combined with diphtheria and tetanus toxoids was compared with that of British whole-cell diphtheria/tetan us/pertussis (DTP) vaccine both in laboratory assays for potency, toxi city and immunogenicity, and for reactogenicity and immunogenicity in infants. Clinical responses were evaluated in double blind randomized Phase II trials using 3/5/9 month and 2/3/4 month schedules. The acell ular DTPs had much lower toxicity than whole-cell DTP in laboratory te sts and were significantly less pyrogenic than whole-cell DTP under bo th schedules. Local reactions were not consistently lower in acellular than whole-cell vaccinees and varied with the source of the diphtheri a and tetanus antigens used. Differences in endotoxin level and conten t of active pertussis toxin (PT) between acellular DTP vaccines were n ot clinically significant. The reactogenicity advantage of the acellul ar vaccines was substantially reduced under the 2/3/4 month schedule d ue to the reduced reactogenicity of the whole-cell DTP vaccine when gi ven at a younger age. There was no relationship between antigen conten t measured in micrograms per dose and ELISA antibody responses to fila mentous haemagglutinin (FHA) and PT in infants, nor was murine immunog enicity predictive of immunogenicity in humans. Antibody response to P T was attenuated in the whole-cell group under the 2/3/4 month schedul e but was unaffected in the group receiving acellular vaccines with in dividually purified components; antibody response to pertactin (69 kDa antigen) was similar in recipients of the whole-cell and component ac ellular vaccines under the 2/3/4 month schedule. PT antibody persisten ce until 4-5 years of age was significantly better in recipients of th e component acellular than either the whole-cell vaccine or the co-pur ified acellular vaccine under the 3/5/9 month schedule. However, dipht heria antitoxin levels were reduced in acellular vaccine recipients un der both schedules, Despite significantly lower tetanus potencies of t he acellular vaccines in laboratory tests, no differences were found i n tetanus anti-toxin responses in children. Copyright (C) 1997 Elsevie r Science Ltd.