Evaluation of the protective efficacy of Haemophilus influenzae type b vaccines in an animal model.
The infant rat model for Haemophilus influenzae type b (Hib) disease was modified to test the protective efficacy of candidate vaccines. The administration of 0.4 micrograms of polyribosylribitol phosphate (PRP) combined with pertussis vaccine or with diphtheria toxoid-tetanus toxoid-pertussis vaccine (DTP) to infant rats at 5, 10, and 15 days of age resulted in significant (P less than 0.001) protection against Hib bacteremia after challenge at 20 days of age. A dose-response effect was demonstrated, and suppression of the protective effect was noted with high doses of PRP. The administration of pertussis vaccine alone or DTP alone did not protect against Hib bacteremia. The degree of protection against Hib bacteremia correlated (P less than 0.005) with the serum anti-PRP antibody response measured before bacterial challenge. High-molecular-weight PRP preparations administered alone or in combination with pertussis vaccine were less effective than standard PRP combined with pertussis vaccine. These data compare favorably with the antibody response in human infants receiving the same vaccines. The observations in this animal model should facilitate the development and testing of other vaccine preparations for human infants.
D000375:Aging; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001428:Bacterial Vaccines / Q000276:immunology*; D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006192:Haemophilus Infections / Q000517:prevention & control*; D006193:Haemophilus influenzae / Q000276:immunology*; D008583:Meningitis, Haemophilus / Q000517:prevention & control; D010567:Pertussis Vaccine; D011134:Polysaccharides / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000517:prevention & control; D013745:Tetanus Toxoid; D014611:Vaccination
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D004338:Drug Combinations; D010567:Pertussis Vaccine; D011134:Polysaccharides; D013745:Tetanus Toxoid; C008984:polyribitol phosphate