Laboratory investigation of immune responses to acellular pertussis vaccines when used for boosting adolescents after primary immunisation with whole cell pertussis vaccines: a comparison with data from clinical study.
The lack of unequivocal immunological correlates of human protection and an absence of a validated animal model for acellular pertussis vaccines, compounded by limited opportunity to undertake efficacy studies in humans and laboratory evaluation side by side, has made it difficult to compare vaccines and formulations. In the present study, the effect on the booster response to pertussis in adolescents primed in infancy with whole cell pertussis vaccine, of three low dose acellular pertussis/diphtheria/tetanus toxoid (TdPa) formulations with or without inactivated poliomyelitis vaccine (IPV) components, was investigated. To assess the relationship between laboratory vaccine evaluation and clinical trial performance, parallel evaluation of the same TdPa vaccines were carried out in a mouse booster model with whole cell pertussis vaccine priming. Prior to boosting, the clinical subjects had low cell mediated immune responses (CMI) responses to pertussis vaccine components. After boosting, all TdPa formulations stimulated CMI responses to the pertussis vaccine components assessed. The booster responses to the pertussis antigens remained skewed towards Th1 type even though acellular pertussis vaccines were used. In general the antibody and CMI responses to pertussis antigens in the mouse model followed the trend seen in the human subjects. Protection against aerosol challenge with virulent Bordetella pertussis was related to the magnitude of the antibody and CMI responses in the mouse model. As in the human subjects, the responses remained skewed towards Th1 type.
National Institute for Biological Standards and Control, Division of Bacteriology, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
Elinor
E
Reynolds
Barry
B
Walker
Dorothy
D
Xing
Joanna
J
Southern
Catpagavalli
C
Asokanathan
Belinda
B
Dagg
Michael
M
Corbel
Elizabeth
E
Miller
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001886:Bordetella pertussis / Q000276:immunology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008168:Lung / Q000382:microbiology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014917:Whooping Cough / Q000503:physiopathology / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D016207:Cytokines; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D011054:Poliovirus Vaccine, Inactivated