Development of a guinea pig model to assess immunogenicity of Haemophilus influenzae type b capsular polysaccharide conjugate vaccines.
There is currently no animal model which reliably predicts the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines in human infants. We evaluated various Hib vaccines in guinea pigs using techniques similar to the United States potency test for adsorbed diphtheria and tetanus toxoids with a view to developing a method for evaluating the potency of a combined adsorbed tetanus, diphtheria, pertussis and Hib conjugate vaccine. Groups of 6-8 guinea pigs received 1.5 single human doses of vaccine at 0 and at 6 or 8 weeks and were bled at 6 weeks and 2 weeks after the booster injection. Total antibodies to polyribosylribitolphosphate (PRP), the Hib capsular polysaccharide, were measured in individual animals and in serum pools by radioimmunoassay. The relative antibody responses of guinea pigs to Hib conjugate vaccines qualitatively resembled those of human infants. Unconjugated polysaccharide was not immunogenic; PRP-D produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPMBL) produced a low response to the first dose and a strong anamnestic response to the booster (geometric mean anti PRP > 1 micrograms ml-1). PRP-OMP uniquely produced a strong response after the first dose which was further boosted by the second dose. Experimental Hib-T vaccine lots with low levels of conjugation were poorly immunogenic in guinea pigs. Combinations of DTP and Hib-T vaccines showed equivalent or greater immunogenicity than Hib-T alone. We propose that the guinea pig model may be useful to verify the immunogenicity of PRP conjugate vaccines and for pre-clinical evaluations of DTP-Hib combination vaccines containing PRP conjugates.
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D016667:Bacterial Capsules; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D018073:Haemophilus Vaccines / Q000276:immunology* / Q000494:pharmacology; D007117:Immunization, Secondary; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000494:pharmacology; D013745:Tetanus Toxoid / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology / Q000494:pharmacology
D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; C044237:Haemophilus influenzae type b polysaccharide vaccine; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate