title: Development of a guinea-pig model for potency/immunogenicity evaluation of diphtheria, tetanus acellular pertussis (DTaP) and Haemophilus influenzae type b polysaccharide conjugate vaccines.
abstract: We have evaluated a guinea pig model for assessing the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines, acellular pertussis vaccine and combination vaccines-consisting of tetanus toxoid (TT), diphtheria toxoid (DT), acellular pertussis vaccine and Hib-TT (Hib-T) conjugate vaccine. The model was based on the United States (US) potency test for TT and DT which requires injection of guinea pigs with a single dose of undiluted vaccine. Guinea pigs showed dose-dependent antibody responses to pertussis toxoid (PTxd) and filamentous haemagglutinin (FHA), two important components of acellular pertussis vaccine. Antibody response of guinea pigs to commercially available Hib conjugate vaccines qualitatively resembled those of human infants. Unconjugated polyribosylribitolphosphate (PRP) was not immunogenic; PRP-D conjugate produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPHBL) produced a low response to the first dose and a strong anamnestic response to the booster dose. PRP-OMP uniquely produced a strong response after the first dose which was boosted by the second dose. In preliminary experiments, injection of guinea pigs with the combined vaccine formulations consisting of TT, DT, whole cell or acellular pertussis vaccine (Ptxd and FHA) and Hib-T conjugate showed that these vaccines were immunogenic when combined, with some effects on the antibody responses of certain components. This model for testing potency/immunogenicity of combined vaccines substantially reduces the number of animals needed to test each lot of vaccine. To reduce the use of animals in testing vaccines further, we propose the use of a Vero cell assay for titrating diphtheria antitoxin and ELISA for measuring IgG antibody to tetanus toxin. The guinea pig model may also be useful for evaluating combination vaccines.
authors.affiliation: Massachusetts Public Health Biologic Laboratories, State Laboratory Institute Boston, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Gupta
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Cecchini
authors.forename: B
authors.initials: B
authors.lastname: Rost
authors.forename: P
authors.initials: P
authors.lastname: Griffin
authors.forename: K
authors.initials: K
authors.lastname: Benscoter
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: L
authors.initials: L
authors.lastname: Montanez-Ortiz
authors.forename: G R
authors.initials: GR
authors.lastname: Siber
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods* / Q000592:standards; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D016667:Bacterial Capsules; D002522:Chlorocebus aethiops; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology / Q000494:pharmacology* / Q000592:standards; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D005260:Female; D006168:Guinea Pigs; D018073:Haemophilus Vaccines / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007114:Immunization; D007223:Infant; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000494:pharmacology*; D012015:Reference Standards; D014481:United States; D017778:Vaccines, Combined / Q000276:immunology / Q000494:pharmacology / Q000592:standards; D018074:Vaccines, Conjugate / Q000276:immunology / Q000494:pharmacology / Q000592:standards; D014709:Vero Cells
chemical_list: D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D011135:Polysaccharides, Bacterial; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate