Haemophilus influenzae Type b Conjugate Vaccines: Update

PEDIATRICS ◽  
1989 ◽  
Vol 84 (2) ◽  
pp. 386-387
Author(s):  
Keyword(s):  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Geometric Mean ◽  
Protein Molecule ◽  
The United States ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Conjugate Vaccines

The purpose of this statement is to update previous information and recommendations provided by the Committee for the use of Haemophilus influenzae type b conjugate vaccines in view of the licensure of a new product. Our initial recommendations concerned the use of PRP-D, a vaccine consisting of the capsular polysacchanide of H influenzae type b conjugated to diphtheria toxoid, which was licensed for use in December 1987. On December 22, 1988, a second conjugate vaccine was licensed by the US Food and Drug Administration for the prevention of infections caused by H influenzae type b in children 18 months of age or olden. This newly licensed vaccine is a conjugate of H influenzae type b capsular oligosaccharide and a nontoxic mutant diphtheria toxin protein molecule called CRM197. The official designation of this vaccine is "Haemophilus b conjugate vaccine (diphtheria CRM197 protein conjugate)" and it is often referred to as HbOC. No serious adverse reactions have been reported in clinical trials to date. Among 265 infants in the United States between 16 and 23 months of age who received HbOC, 7.2% had temperatures exceeding 38°C, 1.5% had erythema and warmth at the injection site, and 0.8% had localized swelling. Like PRP-D, HbOC is more immunogenic in 18-month-old children than are the unconjugated polysacchanide vaccines (PRP). Among 212 HbOC recipients in the study, the geometric mean anticapsular antibody concentration 1 month after immunization was 13.11 µg/mL. Moreover, 98.1% of these infants had an antibody concentration in excess of 1µg/mL, a concentration associated with protection in a Finnish field trial of unconjugated PRP.

Neonatal Immunization: Response to Haemophilus influenzae Type b-Tetanus Toxoid Conjugate Vaccine

PEDIATRICS ◽  
1995 ◽  
Vol 95 (6) ◽  
pp. 815-822
Author(s):  
Sari Kurikka ◽  
Helena Käyhty ◽  
Heikki Peltola ◽  
Leena Saarinen ◽  
Juhani Eskola ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Tetanus Toxoid ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Natural Decay

Objective. To study the immunogenicity and tolerability of Haemophilus influenzae type b (Hib) conjugate vaccine administered in the neonatal period. Design. Hib capsular polysaccharide (PS)-tetanus toxoid conjugate vaccine (PRP-T) was given to 120 neonates at 2 days of age, followed by PRP-T or the Hib PS vaccine at 4 months and a PRP-T booster at 14 months. Their anti-Hib PS concentrations were compared with those in children receiving PRP-T at 2 and 4 months or at 4 months. Results. No serious adverse reactions were noted. The geometric mean concentration of anti-Hib PS at the age of 2 days was 0.34 µg/mL and at 4 months was 0.12 µg/mL. This was significantly more than the concentration in unimmunized infants at this age and 3.5 times more than expected, taking into account the natural decay of transplacentally acquired antibodies. Such a response was not seen in infants with a high (greater than 3.0 µg/mL) neonatal antibody concentration. The PRP-T vaccine given at 4 months elicited an antibody response in all infants and Hib PS in 62%, indicating immunologic priming. At 14 months a higher percentage of the infants who had received PRP-T at 2 days and 4 months than of those who had received PRP-T at 4 months only had anti-Hib PS concentrations greater than 0.15 µg/mL. All infants responded well to the booster at 14 months. There was no evidence of immunologic tolerance. Conclusions. Neonatal immunization with PRP-T was safe and well tolerated in Finnish infants, and it would be worthwhile to further study its effects in higher risk populations.

Haemophilus influenzae Type b Conjugate Vaccines: Immunization of Children at 15 Months of Age

PEDIATRICS ◽  
1990 ◽  
Vol 86 (5) ◽  
pp. 794-796
Author(s):  
Keyword(s):  
United States ◽  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Outer Membrane Proteins ◽  
The United States ◽  
Haemophilus Influenzae Type ◽  
Invasive Infection ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Conjugate Vaccines

This statement updates previous information and recommendations regarding Haemophilus influenzae type b conjugate vaccines. The four vaccines that have received extensive clinical investigation and/or licensure by the United States Food and Drug Administration (FDA) are listed in the Table. Previously, the Committee recommended that all infants be immunized at 18 months of age with one of the two conjugate vaccines, designated PRP-D and HbOC, that were licensed at that time.1, 2 A third conjugate vaccine, designated PRP-OMP and consisting of the capsular polysaccharide of H influenzae type b complexed with outer membrane proteins of Neisseria meningitidis, was licensed by the FDA in December 1989. Currently, the FDA has approved labeling for PRP-OMP, HbOC, and PRP-D vaccines that states "Administration of Haemophilus b Conjugate Vaccine may be considered for children as young as 15 months of age when it is expected that the child will not return at 18 months for Haemophilus b immunization." After review of the data available on immunogenicity for PRP-D, HbOC, and PRP-OMP administered to children at 15 months of age, the Committee concludes that all children should be immunized at 15 months of age. BACKGROUND Before the introduction of immunization against H influenzae type b, it was estimated that annually approximately 16 000 cases of invasive infection occurred in the United States in children 5 years of age or younger.3 About 26.6% of cases occurred in children 18 months of age or older, and approximately an additional 9.3% occurred in children 15 to 17 months of age.

Immunogenicity of Haemophilus influenzae Type b Polysaccharide-Neisseria meningitidis Outer Membrane Protein Conjugate Vaccine in 2- to 6-Month-Old Infants

PEDIATRICS ◽  
1987 ◽  
Vol 80 (2) ◽  
pp. 283-287
Author(s):  
Allen A. Lenoir ◽  
Paul D. Granoff ◽  
Dan M. Granoff
Keyword(s):  
Membrane Protein ◽  
Haemophilus Influenzae ◽  
Neisseria Meningitidis ◽  
Outer Membrane Protein ◽  
Geometric Mean ◽  
Serum Antibody ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Haemophilus Influenzae Type B ◽  
Type B

Fifty infants, 2 to 6 months of age, were vaccinated with Haemophilus influenzae type b capsular polysaccharide covalently linked to an outer membrane protein from Neisseria meningitidis group B. Subjects were given two injections and were randomly assigned to receive the injections separated by 1 or 2 months. Each dose contained 15 µg of polysaccharide and 51 µg of protein, or approximately twice the amount of polysaccharide as used in our previous trial (Lancet 1986;2:299). Fevers of 38.0° to 38.8°C developed in three infants (6%) within 24 hours after vaccination, but there were no other notable reactions. Following one injection, the geometric mean antibody concentration increased from 0.13 µg/mL in preimmune serum to 1.50 µg/mL in serum obtained 1 to 2 months later (P < .001). After a second injection, there was a further increase in serum antibody (geometric mean = 3.11 µg/mL, P < .007). The geometric mean antibody concentration of the group reimmunized 2 months after the first injection was higher than that in the group reimmunized after 1 month (3.95 v 2.32 µg/mL, P = .05, by analysis of covariance with age as the covariant). These data confirm our previous preliminary observations on the safety and immunogenicity of this new conjugate vaccine in infants 2 to 6 months of age. The data suggest that a 2-month interval between the first and second injections results in higher levels of serum antibody than a 1-month interval.

Interchangeability of Haemophilus influenzae Type b vaccines in the Primary Series: Evaluation of a Two-dose Mixed Regimen

PEDIATRICS ◽  
1996 ◽  
Vol 98 (5) ◽  
pp. 898-904 ◽  
Author(s):  
Kathleen M. Bewley ◽  
Joel G. Schwab ◽  
Gerard A. Ballanco ◽  
Robert S. Daum
Keyword(s):  
Haemophilus Influenzae ◽  
Randomized Clinical Trials ◽  
Geometric Mean ◽  
Serum Antibody ◽  
Area Under The Curve ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Series Evaluation

Objective. To evaluate two- or threedose "mixed" regimens of Haemophilus influenzae type b conjugate vaccines in the priming series. Design. Two randomized clinical trials with 140 and 181 infants, respectively. Setting. Private practices in New Orleans and Chicago. Methods. In trial I, infants received one of four regimens. Two were recommended regimens for polyribosylribitol phosphate (PRP)—meningococcal protein conjugate (M) and PRP—tetanus toxoid conjugate (T). Two mixed regimens consisted of M at 2 months followed by two doses of T or PRP—diphtheria toxoid conjugate (D) at 4 and 6 months. Trial II consisted of three groups. Two were recommended regimens for M and T. The third was a two-dose mixed regimen consisting of M at 2 months and T at 4 months. Parents were interviewed and instructed to record side effects after each vaccination. Serum was assayed for H influenzae type b anticapsular antibody (anti-PRP). Results. Minor differences in safety profiles likely reflected α error. In trial I, M (lot 0884T, one of several known to have had decreased immunogenicity), probably primed for substantial increase in serum antibody when D or T was given at 4 and 6 months. In trial II, infants who received the two-dose mixed regimen (M from immunogenic lot 0116W at 2 months and T at 4 months) had a significantly higher mean area under the curve than recipients of the three-dose TIT regimen when antibody concentration was plotted against age, although the geometric mean anti-PRP antibody concentration for the MT-recipients was significantly lower at 7 months. Conclusions. M used in trial I may have primed infants despite poor immunogenicity. The two-dose mixed regimen (MT-) in trial II produced a mean anti-PRP antibody concentration with higher sustained anti-PRP concentrations from 2 to 7 months, as judged by the area under the curve, but a lower mean anti-PRP antibody concentration at 7 months.

Safety and Immunogenicity of Haemophilus influenzae Type b Oligosaccharide-CRM197 Conjugate Vaccine in Infants Aged 15 to 23 Months

PEDIATRICS ◽  
1990 ◽  
Vol 86 (4) ◽  
pp. 527-534
Author(s):  
Dace Viceps Madore ◽  
Cynthia L. Johnson ◽  
Donna C. Phipps ◽  
Martin G. Myers ◽  
Ronald Eby ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Polysaccharide Antibody ◽  
Covalently Linked

A total of 268 infants aged 15 to 23 months received one dose of a vaccine composed of Haemophilus influenzae type b oligosaccharides covalently linked to the nontoxic diphtheria toxin variant CRM197 (HbOC; HibTITER). Side effects associated with vaccination were infrequent, transient, and mild. One month after a single vaccination, the anti-H influenzae type b capsular polysaccharide antibody concentration rose from a geometric mean prevaccination level of 0.20 µg/mL to 13.77 µg/mL. Of these infants, 99% had a postvaccination level greater than or equal to 1.00 µg/mL, a level associated with long-term protection. The immune response was long-lived: all of the children who were monitored 17 to 27 months after vaccination had concentrations greater than or equal to 1.00 µg/mL. The anti-H influenzae type b capsular polysaccharide antibody generated was predominantly of the IgG isotype and IgG1 subclass. The immune sera had bactericidal activity in vitro and conferred passive protection in the infant rat meningitis model.

Haemophilus influenzae Type b Conjugate Vaccine (Meningococcal Protein Conjugate) (PedvaxHIBTM): Clinical Evaluation

PEDIATRICS ◽  
1990 ◽  
Vol 85 (4) ◽  
pp. 676-681
Author(s):  
Vincent I. Ahonkhai ◽  
Linda J. Lukacs ◽  
Leslie C. Jonas ◽  
Holly Matthews ◽  
Philip P. Vella ◽  
...  
Keyword(s):  
United States ◽  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Clinical Evaluation ◽  
Control Strategies ◽  
The United States ◽  
Haemophilus Influenzae Type ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Protein Conjugate

Although systemic infections caused by Haemophilus influenzae type b occur worldwide, detailed epidemiologic data are available in but a few countries.1-3 The public health impact of morbidity, mortality, and serious sequelae from disease caused by H influenzae type b has stimulated the search for control strategies. In the United States now, active immunoprophylaxis is largely favored over treatment or prophylaxis with antibiotics. This preference stems from three major observations: that high mortality and morbidity persist despite the availability of potent antimicrobial agents, that antibiotic-resistant strains of H influenzae type b have emerged, and that implementation of antimicrobial prophylaxis on a large scale has been unsatisfactory. Moreover, universal vaccination has been projected as offering a higher economic benefit than other control strategies.4 A matter of more proximate importance, however, is the search for H influenzae type b vaccines that will confer protection to all age groups, including infants younger than 18 months of age and subpopulations specifically at risk for invasive disease caused by H influenzae type b. Haemophilus b conjugate vaccine (meningococcal protein conjugate), PedvaxHIBTM (PRP-OMPC), is a conjugate H influenzae type b vaccine developed at Merck Sharp & Dohme Research Laboratories that now is undergoing extensive clinical evaluation to assess its prospects for disease control when first administered in early infancy. This is an interim report of results obtained in studies conducted in diverse locations throughout the United States. METHODS Study protocols were approved by Merck Sharp & Dohme Research Laboratories and the Institutional Review Board of each center. Written informed consent was obtained from the parents of subjects at the time of enrollment into each study.

Comparative Immune Responses to Haemophilus influenzae Type b Polysaccharide and a Polysaccharide-Protein Conjugate Vaccine

PEDIATRICS ◽  
1990 ◽  
Vol 85 (4) ◽  
pp. 648-650
Author(s):  
Kwang Sik Kim ◽  
Victor K. Wong ◽  
Robert Adler ◽  
Evan A. Steinberg
Keyword(s):  
United States ◽  
Los Angeles ◽  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
The United States ◽  
Invasive Disease ◽  
Haemophilus Influenzae Type ◽  
Haemophilus Influenzae Type B ◽  
Healthy Children ◽  
Type B

Haemophilus influenzae type b is the most common cause of bacterial meningitis in children in the United States. Antibody to the capsular polysaccharide of this organism, polyribosylribitol-phosphate (PRP), is important in protecting against invasive disease. In 1985, H influenzae type b vaccine containing only PRP was licensed in the United States for use in children 24 to 59 months of age. Studies conducted in the United States and Finland have shown that PRP vaccine is safe and immunogenic in children older than 18 months of age.1,2 In Finland, an efficacy of approximately 80% was obtained when PRP vaccine was used to prevent invasive disease caused by H influenzae type b in children older than 24 months of age.3 The immunogenicity of the PRP vaccine in children 18 to 23 months of age, however, was not clearly established. Reported rates of seroconversion after receipt of a single dose of PRP vaccine ranged from 20% to 75%1.3-5 The purpose of our studies was to evaluate the immunogenicity y of PRP vaccines and of conjugate vaccine (PRP-Neisseria meningitidis outer membrane protein complex [PRP-OMPC]) in children from the Los Angeles area. First, we conducted a randomized, prospective study to compare the immunogenicity of the PRP vaccines produced by three manufacturers. A total of 147 healthy children between the ages of 18 and 58 months were recruited from Childrens Hospital of Los Angeles and Kaiser Foundation Hospital, Los Angeles, to receive, according to a prepared randomization schedule, 25 µg of the following PRP vaccines: Hib-Immune, lot 184-669, 190-654; Hib-Vax, lot 7L91071, 7D91043; or b-CAPSA I, lot M087BD, M068BC.

Opsonophagocidal Activity in Sera From Infants and Children Immunized With Haemophilus influenzae Type b Conjugate Vaccine (Meningococcal Protein Conjugate)

PEDIATRICS ◽  
1990 ◽  
Vol 85 (4) ◽  
pp. 694-697
Author(s):  
Barry M. Gray
Keyword(s):  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Good Health ◽  
The United States ◽  
Infants And Children ◽  
Haemophilus Influenzae Type ◽  
Haemophilus Influenzae Type B ◽  
Type B ◽  
Group B

Immunization with Haemophilus influenzae type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) has resulted in limited and variable antibody radioimmunoassay in infants younger than 2 years of age. Although an H influenzae type B vaccine has been in use for several years, it is not used now for the age group at greatest risk for disease. In an effort to enhance immunogenicity, PRP has been coupled to various carrier proteins and to an outer membrane protein complex (OMPC) from Neisseria meningitidis group B.1,2 The latter approach has yielded a vaccine that elicits a good antibody response after a single 15-µg dose of vaccine in infants as young as 2 months of age, as measured by radioimmunoassay and immune bacteriolysis.3,4 In this report we describe the results of a pilot study using this H influenzae type B conjugate vaccine, PedvaxHIB, in children from 2 months to 4 years of age. Three different vaccine lots were examined for consistency of response. Sera were measured for antibody levels by radioimmunoassay and for functional activity using an opsonophagocytic assay using human adult neutrophils. These assays correlated well and demonstrated the excellent immune response and biologic activity of sera from infants vaccinated with this unique H influenzae type B conjugate vaccine. MATERIALS AND METHODS Subjects Infants and children were part of a multicenter study to assess the safety and immunogenicity of PedvaxHIB.3 They ranged in age from 2 to 51 months and were from various socioeconomic backgrounds and geographic areas of the United States. All were in good health, and informed consent was obtained from the parents of all participants.

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