The performance of four acellular
pertussis vaccines containing between two and five
pertussis antigens combined with
diphtheria and
tetanus toxoids was compared with that of British whole-cell
diphtheria/
tetanus/
pertussis (
DTP) vaccine both in laboratory assays for potency, toxicity 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 acellular DTPs had much lower toxicity than whole-cell DTP in laboratory tests and were significantly less pyrogenic than whole-cell DTP under both schedules. Local reactions were not consistently lower in acellular than whole-cell vaccinees and varied with the source of the
diphtheria and
tetanus antigens used. Differences in
endotoxin level and content of active
pertussis toxin (PT) between acellular DTP
vaccines were not clinically significant. The reactogenicity advantage of the
acellular vaccines was substantially reduced under the 2/3/4 month schedule due to the reduced reactogenicity of the whole-cell
DTP vaccine when given at a younger age. There was no relationship between
antigen content measured in micrograms per dose and ELISA antibody responses to filamentous haemagglutinin (FHA) and PT in infants, nor was murine immunogenicity predictive of immunogenicity in humans. Antibody response to PT was attenuated in the whole-cell group under the 2/3/4 month schedule but was unaffected in the group receiving
acellular vaccines with individually purified components; antibody response to
pertactin (69 kDa
antigen) was similar in recipients of the whole-cell and component
acellular vaccines under the 2/3/4 month schedule. PT antibody persistence until 4-5 years of age was significantly better in recipients of the component acellular than either the whole-cell
vaccine or the co-purified
acellular vaccine under the 3/5/9 month schedule. However,
diphtheria antitoxin levels were reduced in
acellular vaccine recipients under both schedules. Despite significantly lower
tetanus potencies of the
acellular vaccines in laboratory tests, no differences were found in
tetanus anti-toxin responses in children.