Immunogenicity of Haemophilus influenzae type b polysaccharide--diphtheria toxoid conjugate vaccine in adults
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The Haemophilus influenzae type b (Hib) conjugate vaccine (PRP-D) shows enhanced immunogenicity compared to the conventional polysaccharide vaccine (PRP) in adults. While PRP-D elicits higher initial antibody levels, the duration of this effect is transient.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- The capsular polysaccharide (PRP) of Haemophilus influenzae type b (Hib) is poorly immunogenic in infants.
- Developing effective Hib vaccines is crucial for preventing invasive diseases.
Purpose of the Study:
- To evaluate the immunogenicity and safety of a novel conjugate vaccine (PRP-D) linking Hib polysaccharide to diphtheria toxoid.
- To compare the antibody response to PRP-D with a conventional PRP vaccine in adult volunteers.
Main Methods:
- Adult volunteers received two doses of either PRP-D or PRP vaccine.
- Serum anti-PRP antibody concentrations, IgG levels, and functional activity (bactericidal and passive protection) were measured.
- Antibody responses were compared between the two vaccine groups at various time points.
Main Results:
- PRP-D was significantly more immunogenic than PRP after a single dose, inducing higher total and IgG anti-PRP antibody levels.
- While PRP-D initially led to higher antibody concentrations, a transient decline was observed after the second dose.
- Both vaccines induced biologically active anti-PRP antibodies, as evidenced by bactericidal and passive protection assays.
Conclusions:
- The PRP-D conjugate vaccine enhances immunogenicity in adults compared to the conventional PRP vaccine.
- The increased antibody levels induced by PRP-D are biologically active but may be transient.
- Further research may be needed to optimize the duration of immune response for conjugate Hib vaccines.
Abstract:
The capsular polysaccharide of Haemophilus influenzae type b is a poor immunogen in human infants. In an attempt to enhance immunogenicity, this polysaccharide was covalently coupled to diphtheria toxoid and the conjugate tested as a vaccine in adult volunteers. Two injections of PRP-D vaccine were given, separated by one month. The anti-PRP antibody responses in this group were compared with those in a group receiving a comparable dose (20 micrograms) of conventional PRP vaccine. Both vaccines were well tolerated. A single injection of PRP-D was significantly more immunogenic than PRP, eliciting higher serum concentrations of total anti-PRP antibody 1 month later (geo means of 248 and 62 micrograms/ml, respectively; P less than 0.001). In addition, higher concentrations of IgG anti-PRP antibody were observed in the PRP-D group (P less than 0.001). One month after reinjection of vaccine, subjects receiving PRP-D showed a small but significant decline in total antibody (P = 0.03), whereas the serum antibody concentrations in the group that received PRP remained unchanged. At 12 months, the antibody concentrations of the two groups were not significantly different. Bactericidal activity and passive protection activity (infant rat model) were tested in pooled sera from the three highest and three lowest responders in each vaccine group; both PRP and PRP-D vaccines induced biologically active anti-PRP antibody. Thus PRP-D was found to elicit biologically active serum antibody and to be more immunogenic in adults than PRP vaccine; however, the duration of higher concentrations of antibody was transient.