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.

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.

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.

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.

In vitro antibody response of human lymphocytes to the Haemophilus influenzae type b capsular polysaccharide

1993 ◽  
Vol 15 (2-3) ◽  
pp. 247-258 ◽  
Author(s):  
Carla C. A. M. Peeters ◽  
Anne-Marie J. Tenbergen-Meekes ◽  
Jan T. Poolman ◽  
Ben J. M. Zegers ◽  
Ger T. Rijkers
Keyword(s):  
Antibody Response ◽  
Haemophilus Influenzae ◽  
Capsular Polysaccharide ◽  
Human Lymphocytes ◽  
Haemophilus Influenzae Type ◽  
Haemophilus Influenzae Type B ◽  
Type B

Immunogenicity of Haemophilus influenzae Type b Capsular Polysaccharide Vaccines in 18-Month-Old Infants

PEDIATRICS ◽  
1987 ◽  
Vol 80 (3) ◽  
pp. 351-354
Author(s):  
J. O. Hendley ◽  
J. G. Wenzel ◽  
K. M. Ashe ◽  
J. S. Samuelson
Keyword(s):  
Haemophilus Influenzae ◽  
Capsular Polysaccharide ◽  
Current Data ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Type B ◽  
Systemic Reactions ◽  
Healthy Infants ◽  
Younger Age ◽  
Covalently Linked

Haemophilus influenzae vaccine containing polyribosyl ribitol phosphate (PRP) or PRP covalently linked to diphtheria toxoid (PRP-D) was given to 94 healthy infants 17 to 22 months of age at the same time, but not at the same site, as a diphtheria-tetanus-pertussis booster. Systemic reactions were similar in the two vaccine groups and resembled those expected with the diphtheria-tetanus-pertussis injection alone. Six (13%) and seven (14%) of the PRP and PRP-D recipients, respectively, had minor local reactions to the Haemophilus vaccine. Among the 77 children who were not already naturally immune (ie, anti-PRP antibody concentration of ≤0.15 µg of protein per milliliter) before vaccination, PRP-D was significantly more effective than PRP in inducing protective levels of antibody. Only 15 (43%) of the 35 nonimmune PRP recipients achieved a concentration of ≥0.15 µg/mL and only seven (20%) reached a concentration ≥1.0 µg/mL following vaccination. In contrast, 34 (81%) of the 42 nonimmune recipients of PRP-D had a concentration of ≥0.15 µg/mL following vaccine and 32 (62%) had a concentration of ≥1.0 µg/mL (P ≤ .001). These results suggest that more than one-half of nonimmune 18-month-old infants will not respond to PRP with protective levels of antibody. In light of the current data, recommendation for revaccination at 24 months of age for those immunized at any younger age is appropriate.

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