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

A guinea pig model to assess the immunogenicity of a combination vaccine co ntaining diphtheria, tetanus and acellular pertussis (DTaP) Vaccine and Hae mophilus influenzae type b (Hib) capsular polysaccharide conjugated to teta nus toroid (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 su bcutaneous injection of groups of 10 animals twice at an interval of four w eeks with 1/10 of a single human dose of various formulations of combinatio n vaccines, DTaP or HibT vaccine. The animals were bled at 4 and 6 weeks an d IgG or total antibodies to various components were determined by ELISA or RIA. The guinea pig immunogenicity model included groups of animals inject ed subcutaneously twice at an interval of six weeks with 15 times the singl e human dose of various formulations. The animals were bled at 4, 6 and 8 w eeks and serum samples were tested for antibodies to Various components by ELISA, RIA and/or neutralization tests. Additionally, potency of tetanus an d diphtheria components was assessed as per the US Food and Drug Administra tion's regulations. Aluminium phosphate (AlPO4) adsorbed HibT vaccine or Hi bT as a combination with AlPO4 adsorbed DTaP vaccine showed significant inc reases in IgG antibodies to tetanus toxin in mice as well increased tetanus antitoxin levels in guinea pigs as compared to soluble HibT vaccine. In ge neral, combining DTaP and HibT vaccines did not affect the antibody levels to tetanus and diphtheria toxoids whereas DTaP-HibT combination vaccine eli cited 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 a lone whereas guinea pigs consistently showed lower anamnestic responses to Hib for combination formulations than for HibT alone. Reducing the amount o f HibT and/or tetanus toxoid in the combination formulations reduced this s uppression of Hib antibody response in guinea pigs. Suppression of Hib anti body response in combination vaccines has also been reported from recent cl inical trials. Based on the results from this study, it appears that the gu inea pig model may be able to predict the human response to various compone nts of combination vaccines. (C) 1999 The International Association for Bio logicals.