A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for protective immunogenicity in 25 previously PRP-unimmunized children who had failed to develop protective PRP antibody levels (< 1 microg/ml) after prior invasive Hib disease at median age 10 months. Children under 21 months of age at time of PRP-T immunization received one, two or three doses. Serum was obtained for total PRP antibody, complement mediated bactericidal activity and specific IgG1 and IgG2 PRP antibodies before (n = 25), 1 to 2 months (n = 24) and > 5 months (n = 13) after completed vaccination. One to 2 months after immunization, all but one patient developed > 1 microg/ml of antibody (geometric mean level 50.7 microg/ ml). The non-responder developed protective antibody levels when tested at 6 months after vaccination. Twenty out of 22 sera had detectable complement mediated bactericidal activity (median dilution titer 1:24), 1-2 months after vaccination. Three patients failed to demonstrate PRP antibodies in the IgG1 or IgG2 subclasses, although two of them had protective (> 1 microg/ml) total antibody levels. The second post immunization sera showed persistence of the total PRP antibody levels (geometric mean level 38.2 microg/ml) as well as of the bactericidal activity (median dilution titer 1:32).
Conclusion: PRP-T conjugate vaccine is able to elicit a protective immune response in children who have low or unmeasurable PRP antibody levels after a systemic Hib infection.