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Haemophilus influenzae type b conjugate vaccines: a review of efficacy data
1Oxford Vaccine Group, John Radcliffe Hospital, England.
Insights
Haemophilus influenzae type b (Hib) conjugate vaccines have demonstrated high protective efficacy in infants, paving the way for potential disease elimination. Widespread infant immunization with Hib conjugate vaccines is crucial for controlling this childhood pathogen.
Area of Science:
- Pediatric Infectious Diseases
- Vaccinology
- Immunology
Background:
- Haemophilus influenzae type b (Hib) is a significant cause of childhood illness.
- Early Hib vaccines using polyribosylribitol phosphate (PRP) were ineffective in infants.
- Protein conjugation of PRP enhanced immunogenicity, enabling infant protection and memory response.
Purpose of the Study:
- To review clinical trials assessing the protective efficacy of Hib conjugate vaccines in infants.
- To examine the real-world effectiveness of Hib conjugate vaccines in national immunization programs.
Main Methods:
- Review of prospective clinical trials of various Hib conjugate vaccines.
- Analysis of post-introduction effectiveness data from countries with routine infant immunization schedules.
Main Results:
- All tested Hib conjugate vaccines demonstrated high protective efficacy in infants, with PRP-D being an exception in a specific high-disease-incidence population.
- PRP-OMP showed efficacy after a single dose, and PRP-T was effective with an accelerated schedule.
- Real-world effectiveness of these vaccines has been consistently impressive, especially with high coverage.
Conclusions:
- Hib conjugate vaccines are highly effective in preventing Hib disease in infants.
- Widespread infant immunization with Hib conjugate vaccines can lead to the elimination of Hib disease, particularly in populations with high vaccine coverage.
Background:
The development of a vaccine against Haemophilus influenzae type b (Hib) was stimulated by its recognition as a major pathogen of early childhood. The first vaccine to be developed was composed of the capsular polysaccharide of the organism, polyribosylribitol phosphate (PRP), and although effective in older children, it failed to protect those <2 years of age, the group with the highest burden of disease. The conjugation of PRP to protein led to a group of vaccines with enhanced immunogenicity and the ability to induce immunologic memory and thus the potential to protect in infancy.
Objectives:
To review the trials of Hib conjugate vaccines in which protective efficacy in infants has been assessed and the experience in countries in which Hib conjugate vaccines have been introduced into the routine infant immunization schedule.
Discussion:
Each of the Hib conjugate vaccines [PRP-diphtheria toxoid conjugate (PRP-D), PRP conjugated to outer membrane protein of Neisseria meningitidis group B (PRP-OMP), PRP oligosaccharides conjugated to mutant diphtheria toxin CRM197, (HbOC) and PRP conjugated to tetanus toxoid (PRP-T)] has been subjected to prospective clinical trials and all have demonstrated high protective efficacy with one exception: that of the least immunogenic vaccine, PRP-D, when used in a Native American population with a high level of natural disease. The trials have used different populations and different schedules, which limits conclusions about relative efficacies. However, it seems likely that all the vaccines are capable of high efficacy in populations with low levels and late age of Hib disease. Three vaccines (PRP-D, PRP-OMP, PRP-T) have been tested in populations with high rates of disease and only PRP-D has been found lacking. As predicted by immunogenicity data, PRP-OMP affords efficacy after one dose, and PRP-T is efficacious with an accelerated schedule. Of more practical significance the effectiveness of these vaccines when introduced into populations has been uniformly impressive.
Conclusions:
Particularly where vaccine coverage is high, it is now likely that Hib disease can be eliminated using Hib conjugate vaccines in infancy.