| Evaluation of a guinea pig model to assess interference in the immunogenicity of different components of a combination vaccine comprising diphtheria, tetanus and acellular pertussis (DTaP) vaccine and haemophilus influenzae type b capsular polysaccharide conjugate vaccine. | |
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MedLine Citation:
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PMID: 10600208 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A guinea pig model to assess the immunogenicity of a combination vaccine containing diphtheria, tetanus and acellular pertussis (DTaP) vaccine and Haemophilus influenzae type b (Hib) capsular polysaccharide conjugated to tetanus toxoid (HibT) was evaluated comparatively with the mouse immunogenicity test to study the effect of combining these antigens on the immunogenicity of various components. The immunogenicity test in mice was performed by subcutaneous injection of groups of 10 animals twice at an interval of four weeks with 1/10 of a single human dose of various formulations of combination vaccines, DTaP or HibT vaccine. The animals were bled at 4 and 6 weeks and IgG or total antibodies to various components were determined by ELISA or RIA. The guinea pig immunogenicity model included groups of animals injected subcutaneously twice at an interval of six weeks with 1.5 times the single human dose of various formulations. The animals were bled at 4, 6 and 8 weeks and serum samples were tested for antibodies to various components by ELISA, RIA and/or neutralization tests. Additionally, potency of tetanus and diphtheria components was assessed as per the US Food and Drug Administration's regulations. Aluminium phosphate (AIPO(4)) adsorbed HibT vaccine or HibT as a combination with AIPO(4)adsorbed DTaP vaccine showed significant increases in IgG antibodies to tetanus toxin in mice as well increased tetanus antitoxin levels in guinea pigs as compared to soluble HibT vaccine. In general, combining DTaP and HibT vaccines did not affect the antibody levels to tetanus and diphtheria toxoids whereas DTaP-HibT combination vaccine elicited significantly lower IgG antibodies to pertussis toxin and filamentous haemagglutinin than DTaP vaccine alone, particularly after first injection. Mice showed similar Hib antibody responses for the combination and HibT alone whereas guinea pigs consistently showed lower anamnestic responses to Hib for combination formulations than for HibT alone. Reducing the amount of HibT and/or tetanus toxoid in the combination formulations reduced this suppression of Hib antibody response in guinea pigs. Suppression of Hib antibody response in combination vaccines has also been reported from recent clinical trials. Based on the results from this study, it appears that the guinea pig model may be able to predict the human response to various components of combination vaccines. |
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Authors:
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R K Gupta; R Anderson; D Cecchini; B Rost; J Xu; K Gendreau; D L Saroff; C Marchant; G R Siber |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biologicals : journal of the International Association of Biological Standardization Volume: 27 ISSN: 1045-1056 ISO Abbreviation: Biologicals Publication Date: 1999 Jun |
Date Detail:
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Created Date: 2000-01-14 Completed Date: 2000-01-14 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9004494 Medline TA: Biologicals Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 167-76 Citation Subset: IM |
Copyright Information:
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Copyright 1999 The International Association for Biologicals. |
Affiliation:
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Massachusetts Public Health Biologic Laboratories, 305 South St, Boston, MA, 02130, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacterial Capsules Diphtheria-Tetanus-Pertussis Vaccine / immunology* Diphtheria-Tetanus-acellular Pertussis Vaccines Disease Models, Animal Drug Interactions Guinea Pigs Haemophilus Vaccines / immunology* Humans Mice Polysaccharides, Bacterial / biosynthesis, immunology* Vaccines, Combined / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Capsules; 0/Diphtheria-Tetanus-Pertussis Vaccine; 0/Diphtheria-Tetanus-acellular Pertussis Vaccines; 0/Haemophilus Vaccines; 0/Haemophilus influenzae type b polysaccharide vaccine; 0/Polysaccharides, Bacterial; 0/Vaccines, Combined |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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