Assessment of anti-HBs antibody concentration in children with juvenile idiopathic arthritis treated with biological drugs, vaccinated against viral type B hepatitis in infancy

One hundred forty-one children of 5 to 59 months of age were immunized with a single intramuscular dose of 0.67, 3.3, 17, or 67 μg polyribophosphate (PRP), the capsular antigen ofHemophilus influenzae, type b. The immunizations were well tolerated, particularly at doses of .67 to 17 μg. Antibody activity was measured by radioactive antigen binding, using3H-labelled PRP. Doses of 3.3 and 17 μg produced significant antibody rises in nearly 90% of recipients; 0.67 and 67 μg in approximately half. The geometric mean titers were similar at three and six weeks after immunization and were greater with the middle doses. The net antibody increase in responding children was strongly age dependent, but was not related to the preimmunization antibody concentration. Rises in serum bactericidal activity against H. influenzae type b generally accompanied rises in antibody concentration as measured by the antigen-binding assay. A recently developed Haemophilus influenzae type b capsular polysaccharide vaccine was given to 48 977 children 3 months to 5 years of age; an equal number of children receiving group A meningococcal vaccine served as controls. The protection as well as serum antibody response was strongly age dependent. Among children who had received the H. influenzae type b vaccine when 18 months of age or older, there were no cases of bacteremic disease caused by H. influenzaetype b in the first year after vaccination. At the same time 11 such cases were seen in the control group of the same age, a highly significant difference. In the second year after vaccination two cases occurred in the H. influenzae type b-vaccinated group, five in the meningococcal-group A vaccinated group. No protection was seen among children who had been younger than 18 months when vaccinated, even if they received a booster dose of the vaccine. The serum antibody response to the H. influenzae type b polysaccharide, measured by radioimmunoassay, was poor in children below 18 months of age and good in those above it. No effect of the vaccine could be seen on the nasopharyngeal carriage of H. influenzae type b, which was approximately 6% in this age group. Adverse effects of the vaccine were mild.

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RESPONSES OF CHILDREN IMMUNIZED WITH THE CAPSULAR POLYSACCHARIDE OF HEMOPHILUS INFLUENZAE, TYPE b

PEDIATRICS ◽

10.1542/peds.52.5.637 ◽

1973 ◽

Vol 52 (5) ◽

pp. 637-644

Author(s):

David H. Smith ◽

Georges Peter ◽

David L. Ingram ◽

A. Lynn Harding ◽

Porter Anderson

Keyword(s):

Capsular Polysaccharide ◽

Geometric Mean ◽

Antibody Concentration ◽

Antibody Activity ◽

Antigen Binding ◽

Type B ◽

Intramuscular Dose ◽

Hemophilus Influenzae ◽

Age Dependent ◽

Hemophilus Influenzae Type B

One hundred forty-one children of 5 to 59 months of age were immunized with a single intramuscular dose of 0.67, 3.3, 17, or 67µg polyribophosphate (PRP), the capsular antigen of Hemophilus influenzae, type b. The immunizations were well tolerated, particularly at doses of .67 to 17µg. Antibody activity was measured by radioactive antigen binding, using 3H-labelled PRP. Doses of 3.3 and 17µg produced significant antibody rises in nearly 90% of recipients; 0.67 and 67µg in approximately half. The geometric mean titers were similar at three and six weeks after immunization and were greater with the middle doses. The net antibody increase in responding children was strongly age dependent, but was not related to the preimmunization antibody concentration. Rises in serum bactericidal activity against H. influenzae type b generally accompanied rises in antibody concentration as measured by the antigen-binding assay.

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

PEDIATRICS ◽

10.1542/peds.80.2.283 ◽

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.

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

PEDIATRICS ◽

10.1542/peds.98.5.898 ◽

1996 ◽

Vol 98 (5) ◽

pp. 898-904 ◽

Cited By ~ 1

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.

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

PEDIATRICS ◽

10.1542/peds.95.6.815 ◽

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.

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Haemophilus influenzae Type b Conjugate Vaccines: Update

PEDIATRICS ◽

10.1542/peds.84.2.386 ◽

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.

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

PEDIATRICS ◽

10.1542/peds.86.4.527 ◽

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.

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Biologics for the Treatment of Juvenile Idiopathic Arthritis

Current Medicinal Chemistry ◽

10.2174/0929867325666180522085716 ◽

2019 ◽

Vol 25 (42) ◽

pp. 5860-5893 ◽

Cited By ~ 10

Author(s):

Dimitri Poddighe ◽

Micol Romano ◽

Maurizio Gattinara ◽

Valeria Gerloni

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Clinical Evidence ◽

Treatment Options ◽

Lymphocyte Activation ◽

Biological Drugs ◽

Immune Systems ◽

Tnf Α ◽

New Treatment ◽

Biologic Drug ◽

Comprehensive Discussion

Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases in children. Recently, the management of JIA has substantially changed, thanks to the availability of new treatment options, represented by biological drugs or biologics. These drugs modulate the specific mechanisms of the immune systems, such as TNF-α, IL-1 and IL-6 signaling, or lymphocyte activation and/or functioning. In this review, we provide a comprehensive discussion on the current recommendations and clinical evidence regarding the use of the available biologics in the treatment of JIA; moreover, the main pharmacokinetic and pharmacodynamic aspects of any specific biologic drug have been summarized.

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Dynamics of natural immunity caused by subclinical infections, case study on Haemophilus influenzae type b (Hib)

Epidemiology and Infection ◽

10.1017/s0950268800004799 ◽

2000 ◽

Vol 125 (3) ◽

pp. 583-591 ◽

Cited By ~ 12

Author(s):

T. LEINO ◽

K. AURANEN ◽

P. H. MÄKELÄ ◽

H. KÄYHTY ◽

A. K. TAKALA

Keyword(s):

Haemophilus Influenzae ◽

Invasive Disease ◽

Haemophilus Influenzae Type ◽

Antibody Concentration ◽

Natural Immunity ◽

Type B ◽

Force Of Infection ◽

Invasive Infections ◽

Disease Antibody ◽

Antibody Levels

Natural immunity to Haemophilus influenzae type b (Hib) is based primarily on antibodies that are thought to develop in response to subclinical infections. Wide use of conjugated Hib vaccines could lead to decreases in circulating Hib bacteria, thereby diminishing antibody levels in the unvaccinated. We applied a statistical model to estimate the duration of natural immunity to Hib under different forces of infection. Prior to the introduction of conjugated Hib vaccines, new Hib infections were estimated to occur once in 4 years and the antibody concentration to stabilize at a level around 1 μg/ml. In the absence of new stimuli, i.e. infection, 57% of the unvaccinated population would become susceptible to invasive disease (antibody levels < 0·15 μg/ml) in 10 years. Due to an interaction between the force of infection and the duration of immunity, in some situations numbers of invasive infections could increase in unvaccinated cohorts. This theoretical scenario has yet to be observed in practice.

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Cataract Surgery with Intraocular Lens Implantation in Juvenile Idiopathic Arthritis-Associated Uveitis: Outcomes in the Era of Biological Therapy

Journal of Clinical Medicine ◽

10.3390/jcm10112437 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2437

Author(s):

Elena Bolletta ◽

Marco Coassin ◽

Danilo Iannetta ◽

Valentina Mastrofilippo ◽

Raffaella Aldigeri ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Cataract Surgery ◽

Intraocular Lens ◽

Immunosuppressive Treatment ◽

Group Versus ◽

Visual Outcome ◽

Biological Drugs ◽

Systemic Complications ◽

Iol Implantation ◽

Biological Group

This study compared the outcomes of cataract surgery with intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis treated with antimetabolite drugs and systemic corticosteroids (Non-Biological Group) versus patients treated with antimetabolites and biological drugs (Biological Group). A cohort of patients with cataract in JIA-associated uveitis undergoing phacoemulsification with IOL implantation was retrospectively evaluated. The main outcome was a change in corrected distance visual acuity (CDVA) in the two groups. Ocular and systemic complications were also recorded. The data were collected preoperatively and at 1, 12, and 48 months after surgery. Thirty-two eyes of 24 children were included: 10 eyes in the Non-Biological Group and 22 eyes in the Biological Group. The mean CDVA improved from 1.19 ± 0.72 logMAR preoperatively to 0.98 ± 0.97 logMAR at 48 months (p = 0.45) in the Non-Biological Group and from 1.55 ± 0.91 logMAR preoperatively to 0.57 ± 0.83 logMAR at 48 months (p = 0.001) in the Biological Group. The postoperative complications, including synechiae, cyclitic membrane, IOL explantation, glaucoma, and macular edema, were not statistically different between the two groups. An immunosuppressive treatment with biological drugs can improve the visual outcome after cataract surgery in patients with JIA-associated uveitis, but it does not significantly reduce postoperative ocular complications.

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