Biomedical subjects

D M Granoff

Publications and source records attributed to D M Granoff.

At least 55 records · Page 3Linked to original sources

PubMed1993

Effect of immunity to the carrier protein on antibody responses to Haemophilus influenzae type b conjugate vaccines.

The anticapsular antibody responses to some Haemophilus influenzae type b (Hib) conjugate vaccines may be enhanced by prior or simultaneous administration of the carrier protein used in the conjugate. Currently, there are two Hib conjugate vaccines licensed in the USA for use in infants beginning at 2 months of age: Hib polysaccharide coupled to an outer membrane protein complex of Neisseria meningitidis (PRP-OMPC), and Hib oligosaccharides conjugated to CRM197, a non-toxic mutant diphtheria toxin (HbOC). The PRP-OMPC conjugate vaccine is immunogenic in infant monkeys and infant humans in the absence of carrier priming or additional carrier vaccination. The mechanism responsible for this immunogenicity is unknown but may relate to the adjuvanticity of the OMPC carrier. In contrast, data from infant rhesus monkeys and infant humans suggest that there may be a need for vaccination with diphtheria toxoid in order to maximize anti-PRP antibody responses to the HbOC conjugate. In addition, immunization with HbOC alone appears to be insufficient to elicit an antibody response to diphtheria toxoid. Thus, the need for additional vaccination with diphtheria toxoid in order to generate consistent anti-PRP antibody responses to HbOC may be a result of failure of the CRM197 protein carrier to elicit T-cell help. In infants in whom diphtheria-tetanus-pertussis (DTP) vaccination is deferred because of medical contraindications, vaccination with the PRP-OMPC conjugate would appear to be preferable to HbOC because of the ability of the former to elicit antibody responses in the absence of diphtheria toxoid vaccination.

Animals↗

PubMed1993

Decreased Haemophilus colonization in children vaccinated with Haemophilus influenzae type b conjugate vaccine.

OBJECTIVE: The incidence of invasive Haemophilus disease has unexpectedly decreased in unvaccinated children since the introduction of conjugate vaccine in the United States. The purpose of this study was to determine whether conjugate vaccination decreases colonization with Haemophilus influenzae type b. DESIGN: This study was a prospective, bimonthly survey of pharyngeal colonization with H. influenzae type b in children attending day care from October 1987 through September 1989. Vaccination status was determined from the medical record. SUBJECTS: We obtained 1188 pharyngeal cultures from 283 healthy children, 18 to 59 months of age; 51 children had received unconjugated polysaccharide vaccine (PRP), and 89 had received conjugate vaccine (94% PRP-diphtheria toxoid). MEASUREMENTS AND RESULTS: Multivariate analysis was used to test the possibility of an association between vaccination status and the rate of colonization with H. influenzae type b. Among children known to be exposed to at least one child with a positive culture result, the efficacy of conjugate vaccination to prevent H. influenzae type b colonization in an unmatched analysis was 64% (95% confidence interval: 5%, 86%; p = 0.02) and in a matched analysis 81% (95% confidence interval: 7%, 96%; p = 0.02). No effect on colonization was found with PRP vaccination. CONCLUSIONS: Conjugate vaccination decreases H. influenzae type b pharyngeal colonization and thereby may decrease transmission of this agent among healthy children.

Bacterial Proteins↗

PubMed1993

Antigenuria in healthy Papua New Guinean children with nasal Haemophilus influenzae type b carriage.

In 100 healthy children under the age of 3 years living in the vicinity of Goroka, Papua New Guinea, the nares were cultured for Haemophilus influenzae type b (Hib), and a urine sample was obtained for measurement of Hib polysaccharide (PS) by ELISA. Hib carriage was detected in nine children and Hib PS was detected in the urine of 11. Hib PS was found in seven of nine Hib nasal carriers compared with four of 91 healthy children without Hib in their nares (p < 0.001). The range of urine antigen concentrations in the two groups was similar (0.6 to 2.7 ng/ml). The relative risk of antigenuria in the carriers, compared with the children with negative nares cultures, was 58 (95% confidence interval, 10.5-324). These data extend previous observations from Hib carriers studied in the United States and show that Hib carriage in children from a developing country is associated with antigenuria. Further studies are needed to determine whether carriers and patients can be differentiated by differences in the magnitude of the concentration of Hib PS excreted in urine.

Antigens, Bacterial↗

PubMed1993

Induction of immunologic memory in infants primed with Haemophilus influenzae type b conjugate vaccines.

The ability of different Haemophilus influenzae type b conjugate vaccines to induce immunologic memory was compared in 381 infants who were vaccinated with one of three conjugate vaccines beginning at 2 months of age. All infants were vaccinated with unconjugated type b capsular polysaccharide, polyribosylribitol phosphate (PRP), at 12 months. In each group, high antibody responses were detected by 6-9 days after vaccination. One month after receiving PRP, infants primed with PRP conjugated to the outer membrane protein of Neisseria meningitidis or PRP oligomers conjugated to the cross-reactive mutant diphtheria protein, CRM197, had twofold higher total anti-PRP antibody concentrations than did infants primed with PRP conjugated to tetanus toxoid (P < .005). After the conjugate and the PRP boost, notable differences were present among vaccine groups with respect to the magnitude of the IgG anti-PRP antibody concentrations and light chain variable region usage as determined by idiotypic analysis. Thus, each of the conjugate vaccines primed infants for the ability to evoke memory antibody responses to PRP, but qualitative and quantitative differences in priming induced by different vaccines may affect their ability to confer protection against disease.

Bacterial Outer Membrane Proteins↗

PubMed1993

Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates. Description of a new lambda light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation. The Collaborative Vaccine Study Group.

Haemophilus influenzae b polysaccharide (Hib PS)-protein conjugate vaccines differ chemically and immunologically. To determine whether anti-Hib PS variable region expression might differ according to vaccine formulation, infants were vaccinated at 2, 4, and 6 mo of age with Hib PS coupled to either meningococcal outer membrane protein complex (Hib PS-OMPC) or tetanus toxoid (Hib PS-T), or Hib PS oligomers coupled to a mutant diphtheria toxin (Oligo-CRM). Two anti-Hib PS idiotypes were measured in sera obtained after the third injection: HibId-1, expressed by anti-Hib PS antibodies having the kappa II-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti-Hib PS antibodies having lambda VII variable regions. HibId-1 was present in 33, 68, and 64% of infants given either Hib PS-OMPC, Oligo-CRM, or Hib PS-T, respectively (P < 0.001). The respective values for HibId-2 were 47, 18, and 10% (P = 0.001). Subjects who were vaccinated with Hib PS-OMPC or Hib PS-T and who produced detectable HibId-1-positive antibody, had significantly higher mean antibody avidity than subjects who did not produce HibId-1 positive antibodies. In contrast, Oligo-CRM evoked high avidity anti-Hib PS antibodies, irrespective of the idiotypic profile. These findings indicate fundamental differences in both variable region content and antibody quality elicited by different Hib PS conjugate vaccines.

Antibodies, Bacterial↗

PubMed1992

Avidity and bactericidal activity of antibody elicited by different Haemophilus influenzae type b conjugate vaccines. The Vaccine Study Group.

OBJECTIVE: Antibody avidity is a measure of the functional affinity of serum antibody to bind to antigen. In this study, we compared the avidity of antibodies elicited by vaccination with three Haemophilus influenzae type b (Hib) conjugate vaccines and investigated the relationship between antibody avidity and the ability of antibody to activate complement-mediated bactericidal activity. DESIGN: A convenience sample of 171 postvaccination serum samples with more than 0.5 microgram/mL of anticapsular antibody, the minimum concentration required for measurement of avidity. The serum samples were obtained from infants participating in immunogenicity trials with Hib capsular polysaccharide (PRP) conjugated to meningococcal outer membrane protein complex (PRP-OMPC) or to tetanus toxoid (PRP-T), or PRP oligomers conjugated to a nontoxic mutant diphtheria toxin, CRM197 (Oligo-CRM). PATIENTS: Healthy infants recruited in private practices. PRIMARY OUTCOME MEASURES: Avidity of vaccine-induced serum anticapsular antibody and serum bactericidal titers. RESULTS: In infants vaccinated at 2, 4, and 6 months of age, Oligo-CRM evoked antibody of higher avidity than PRP-OMPC (P less than .001). The mean avidity of antibody elicited by PRP-T was intermediate, being lower than Oligo-CRM (P less than .02) but higher than PRP-OMPC (P = .001). Also, after one dose, 18-month-old infants given Oligo-CRM had higher avidity antibodies compared with those given PRP-OMPC (P less than .001). Half of the infants in both age groups who were given Oligo-CRM developed antibody avidity of 2.50 nM-1 or greater, whereas more than two thirds of the infants given PRP-OMPC had avidity values of 1.25 nM-1 or less. Antibodies with avidity of 1.25 nM-1 or less were, on average, 6.6-fold less active in assays of complement-mediated bactericidal activity than antibodies with avidity of 2.50 nM-1 or greater (P less than .001). CONCLUSIONS: Oligo-CRM and PRP-T conjugate vaccines elicit higher avidity antibody than PRP-OMPC, and high-avidity antibody is more potent than low-avidity antibody in serum bactericidal assays. Consideration should be given to including measurement of antibody avidity in assessment of new vaccines since avidity may affect the ability of serum antibody to confer protection against disease.

Antibodies, Bacterial↗

PubMed1992

Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants.

OBJECTIVE: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. DESIGN: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. SUBJECTS: A convenience sample of 458 infants recruited largely from private pediatric practices. MEASUREMENTS AND RESULTS: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. CONCLUSIONS: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown.

Age Factors↗

PubMed1992

The biology of Haemophilus influenzae type b vaccination failure.

Vaccination with unconjugated polysaccharide vaccine against Haemophilus influenzae type b (Hib) disease at a median age of 25 months was not effective in a group of children who developed Hib disease at a median age of 35 months. This group had normal serum immunoglobulin concentrations but impaired anticapsular antibody responses to Hib infection and to reimmunization with unconjugated polysaccharide. Another group vaccinated with conjugated polysaccharide vaccine at a median age of 18 months developed Hib disease at a median age of 24 months. Of this group, 40% had subnormal immunoglobulin concentrations, particularly IgG2, and showed impaired antibody responses to Hib infection, whereas those with normal immunoglobulin concentrations showed high antibody responses to Hib infection. In both vaccination failure groups, low antibody responders to infection responded to revaccination with Hib conjugate, and most children expressed the idiotype HibId-1 in convalescent or postrevaccination sera. The presence of this idiotype implies that vaccination failure did not result from an inability to use the V kappa II A2 variable region gene, which is used in the anticapsular antibody response of most healthy children.

Antibodies, Bacterial↗

PubMed1992

G2m(23) immunoglobulin allotype and immunity to Haemophilus influenzae type b.

G2m(23), an allotype on IgG2 molecules, is detected in sera of about two of three Caucasians. Adults who are homozygous for G2m(23) have IgG2 antibody responses to types 14 and 18C pneumococcal polysaccharides fourfold higher than those of homozygous-negative subjects. Adults homozygous for G2m(23) also show higher IgG2 antibody responses to vaccination with Haemophilus influenzae type b (Hib) polysaccharide. Furthermore, adults heterozygous for G2m(23) show IgG2 antibody responses intermediate between responses of those homozygous-positive and homozygous-negative. In contrast, the magnitude of the IgG1 antibody responses of adults to Hib polysaccharide was similar irrespective of G2m(23) genotype status. The magnitude of the IgG antibody responses of children vaccinated with Hib polysaccharide is not affected by G2m(23) status, in part because the IgG subclass responses of children to this antigen are restricted to IgG1. Also, children show no consistent associations between G2m(23) allotype status and the risk of acquiring Hib disease or the risk of Hib vaccination failure.

Bacterial Capsules↗

PubMed1992

Invasive Haemophilus influenzae type b disease in children less than 5 years of age in Minnesota and in Dallas County, Texas, 1983-1984.

During 1983 and 1984, 733 cases of invasive Haemophilus influenzae type b disease in children less than 5 years of age were identified in Minnesota and in Dallas County, Texas. The overall incidence of disease was lower in Minnesota than in Dallas County. However, among urban residents, the rates of disease for whites were similar in the two areas. A higher rate of disease among whites in urban Minnesota compared with rural Minnesota resulted from an increased rate of cases for diagnoses other than meningitis. Local practices might have affected the rate of certain diagnoses, since ascertainment of Hib disease other than meningitis is more dependent on diagnostic practices than is diagnosis of meningitis. These data suggest that the incidence of invasive H. influenzae type b disease is influenced by the racial composition of the population, the rates of disease in specific subgroups, and possibly by local medical practices. Understanding the factors that contribute to the incidence of disease is necessary to interpret variations in different populations and changes over time.

Age Factors↗

PubMed1991

Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine. The Collaborative Study Group.

OBJECTIVE: --Haemophilus influenzae type b (Hib) conjugate vaccines are effective in preventing Haemophilus disease in most children. The reasons why the vaccination fails in some children are unknown. This study investigated host factors in children who developed the disease despite conjugate vaccination. DESIGN, PATIENTS, OUTCOME MEASURES:--A convenience sample of 23 patients in whom Hib disease developed 14 days or more after conjugate vaccination was investigated for the presence of subnormal serum immunoglobulin concentrations and anticapsular antibody responses to Hib disease. We also investigated expression of the Hib idiotype 1 (Hibld-1), a serological marker of a VKII chain that comprises a major portion of the normal variable region repertoire of the antibody response to Hib polysaccharide. The results were compared with those of 149 patients in whom the unconjugated Hib polysaccharide vaccine failed and of 90 unvaccinated patients who developed the disease. RESULTS: --Compared with children in whom the unconjugated polysaccharide vaccination failed, the relative risk of a subnormal serum concentration of IgM, IgA, IgG, and/or IgG2 in the children in whom the conjugate vaccination failed was 4.9 (95% confidence interval [CI], 1.8 to 14; P less than .003) and of IgG2 was 22 (95% CI, 3.5 to 146; P less than .001). With the exception of the children with subnormal serum immunoglobulin concentrations, most of the children with conjugate vaccination failure showed normal or high anticapsular antibody responses to the disease, whereas the children with polysaccharide vaccination failure showed impaired responses. The Hibld-1 was expressed by the majority of the children in both vaccination failure groups and of the unvaccinated patients. CONCLUSIONS: --In most patients, vaccination failure is not attributable to lack of expression of the variable region gene encoding Hibld-1. However, children in whom conjugate vaccination has failed frequently have subnormal serum immunoglobulin concentrations and should be evaluated for immunodeficiency.

Antibodies, Bacterial↗

PubMed1991

Antimicrobial resistance of pneumococci in children with acute lower respiratory tract infection in Pakistan.

87 strains of Streptococcus pneumoniae isolated during three winter seasons (1986-89) from the blood of children with acute lower respiratory tract infection (ALRI) in Pakistan were serotyped and tested for susceptibility to a range of antimicrobial agents. 97% of isolates were resistant to at least one antimicrobial drug. 62% had decreased susceptibility to co-trimoxazole (trimethoprim/sulphamethoxazole) (31% were fully resistant) and 39% were resistant to chloramphenicol. All isolates were susceptible to erythromycin, cefaclor, cephalothin, ceftriaxone, cefuroxime, rifampicin, vancomycin, and clindamycin. 29% of isolates were neither vaccine types nor vaccine-related types. Serotype distribution and antimicrobial susceptibility varied significantly during the three winter seasons. No single serotype was found in all three winters. The findings highlight the need for surveillance of antimicrobial resistance and serotype distribution of S pneumoniae in developing countries as a guide both to the choice of agent for treatment of pneumococcal infections, especially ALRI, and to the formulation of new pneumococcal conjugate vaccines for use in young children.

Child, Preschool↗

PubMed1991

Comparative immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugate vaccines.

There are only minor differences in the immunogenicity of the three Haemophilus b polysaccharide-protein conjugate vaccines licensed in the US when tested in children 17 to 19 months of age. In contrast, there are much greater differences in immunogenicity in 2-month-old infants. At this age, a single dose of PRP-OMPC evokes a strong primary antibody response, whereas repeated doses of HbOC or PRP-D are required to evoke an antibody response. These differences in immunogenicity are noteworthy, but they are not necessarily correlated with differences in the ability of different conjugate vaccines to confer protection against disease. Vaccination with all three of the conjugate vaccines primes infants for the ability to make a booster antibody response to reimmunization with unconjugated PRP vaccine and, possibly, to exposure to the encapsulated bacteria. Although unproven, this priming may be sufficient to confer protection against disease even in the absence of a 'protective' level of serum antibody.

Antibodies, Bacterial↗

PubMed1991

Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children.

OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17- to 19-month-old children in the United States. DESIGN: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15 microgram/ml showed higher antibody responses to vaccination than children with less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with less than or equal to 0.15 microgram/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRP-T in Houston (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0 micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.

Antibodies, Bacterial↗

PubMed1991

An idiotypic marker associated with a germ-line encoded kappa light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide.

Human antibodies specific for the Haemophilus influenzae b polysaccharide (Hib PS) frequently express a cross-reactive idiotype (CRI), and commonly utilize a VL region that is the product of the V kappa II gene A2. To examine further anti-Hib PS V region expression and to determine whether CRI expression is correlated with the V kappa IIA2 chain, we isolated a monoclonal antibody (MAb) reactive with an idiotypic determinant of anti-Hib PS antibodies. This MAb inhibited Hib PS binding but did not react with Ig isotypic determinants. The CRI recognized by this MAb, designated HibId-1, was associated with the Hib PS-combining site since the reactivity of the MAb with anti-Hib PS antibodies could be inhibited by Hib PS. HibId-1 was expressed by 17 of 17 clonally purified and sequence-defined anti-Hib PS antibodies having V kappa IIA2 L chains. In contrast, 0 of 10 anti-Hib PS antibodies having either V lambda, V kappa I, or V kappa III chains expressed HibId-1. Western blot analysis showed that the MAb anti-CRI reacted with isolated anti-Hib PS V kappa IIA2 L chains but not with H chains or other L chains, indicating that the HibId-1 determinant is localized to the V kappa IIA2 chain, and does not require pairing with H chain for expression. Anti-Hib PS antibodies bearing HibId-1 were present in at least 85% of subjects immunized with either free Hib PS or Hib PS coupled to diphtheria toxoid (Hib PS-DT), and comprised on the average 60% of the total vaccine-induced serum anti-Hib PS. HibId-1 expression was not related to age at vaccination inasmuch as infants, children, and adults had similar distributions of HibId-1-positive anti-Hib PS after vaccination with Hib PS-DT. HibId-1 was expressed at a lower frequency and comprised a smaller fraction of the total anti-Hib PS antibody in adult preimmunization sera as compared to post-Hib PS immunization sera, suggesting that immunization preferentially stimulates HibId-1-positive B cells. These data demonstrate that antibodies bearing HibId-1/V kappa IIA2 comprise a predominant component of the anti-Hib PS response induced by immunization, and that this pattern of VL expression is established early in ontogeny.

Adult↗

PubMed1991

In vitro induction of IgG1 and IgG2 secretion by B cells of children who developed invasive haemophilus disease despite vaccination.

Lymphocytes from seven patients who developed Haemophilus influenzae type b (Hib) disease after being vaccinated with Hib polysaccharide vaccine and from one patient who developed disease after conjugate vaccination were investigated for the ability to secrete IgG1 and IgG2, in vitro, in response to a combination of pokeweed and Staphylococcus aureus Cowan I mitogens. The eight patients were selected because they had low anticapsular antibody responses to Hib disease. Only one of the eight children had a history of previous severe, recurrent infections. This child (in whom a polysaccharide vaccine failed) had a deficiency of the second component of complement and also had a subnormal serum concentration of IgG4. Only one of the eight children, an otherwise healthy 54-mo-old with normal serum Ig concentrations, had subnormal mitogen-induced B-cell secretion of IgG1 and/or IgG2. When this child's lymphocytes were separated into T- and B-cell fractions and cocultivated with the respective fractions of the father's lymphocytes, the child appeared to have an intrinsic B-cell defect and normal T cells. There were no significant differences (p greater than 0.3) in the respective geometric means of the in vitro secretion of IgG1 or IgG2 of the B cells from the children with polysaccharide vaccine failure and those of 14 healthy controls of similar ages as the patients (IgG1, 1524 versus 3497 ng/mL per 10(5) lymphocytes; IgG2, 79 versus 89 ng/mL per 10(5) lymphocytes). Thus, despite the presence of impaired serum anticapsular antibody responses to Hib disease, most children who develop Hib disease after Hib polysaccharide vaccination have normal in vitro B-cell secretion of IgG1 and IgG2 in response to mitogens.

B-Lymphocytes↗

PubMed1990

Protective efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid-conjugate vaccine.

We estimated the relative protective efficacy of Haemophilus influenzae type b polysaccharide (PRP) vaccine and PRP-diphtheria toxoid-conjugate (PRP-D) vaccine using data from reports of cases of invasive Haemophilus disease occurring in vaccinated children submitted to the Food and Drug Administration, Rockville, Md, and Washington University, St Louis, Mo. During the first 13 months following licensure of each of the vaccines, there were 127 cases reported in recipients of PRP vaccine vs 17 cases in recipients of PRP-D vaccine. The total number of reported cases for each vaccine is not necessarily comparable, since the extent of vaccine use in the population and the extent of reporting of cases may have been different during the two periods. However, the proportion of reported cases occurring equal to or 14 days or more after vaccination (a period considered sufficient to develop immunity) was significantly greater for PRP vaccine (106 [83%] of 127 cases) compared with PRP-D vaccine (7 [41%] of 17 cases). Based on the ratio of late-onset to early-onset cases observed for PRP vaccine, we would have expected 50 late-onset cases after PRP-D vaccination. Since only 7 late-onset PRP-D vaccine failures were reported (86% fewer than expected), the data suggest that PRP-D vaccine was more effective in preventing disease 14 days or more after vaccination than was PRP vaccine.

Bacterial Capsules↗

PubMed1990

Subnormal serum concentrations of IgG2 in children with frequent infections associated with varied patterns of immunologic dysfunction.

To characterize more fully the immunologic basis for increased susceptibility to infection in patients with low serum concentrations of IgG2, we identified eight infection-prone children, 1 to 2 years of age, with serum IgG2 concentrations greater than 2 SD below the mean for age and followed their serologic and clinical courses for 1 to 3 years. Two of the eight children became clinically and immunologically normal and may have had transient IgG2 deficiency with an exaggerated developmental delay of this late-maturing subclass. The remaining six subjects had persistently subnormal or low-normal serum IgG2 levels and continued to experience frequent infections. All six of these children responded poorly to Haemophilus influenzae type b (Hib) polysaccharide, and four of six responded poorly to Streptococcus pneumoniae type 3 polysaccharide. Both IgG1 and IgG2-specific antibody responses to these vaccines were abnormal. Three of these six children also responded poorly to tetanus toxoid, an antigen that normally induces a predominant IgG1 response. Although five of these six children produced antibodies in response to Hib polysaccharide protein conjugate vaccine, three of four given Hib oligosaccharide CRM conjugate vaccine required booster doses to respond, a pattern of response characteristic of infants less than 6 months of age. Further, although serum concentrations of IgG1 were normal, peripheral blood mononuclear cells from four of six children tested produced extremely small amounts of IgG1 and IgG3 as well as IgG2. Finally, varied patterns of abnormalities of IgG, IgA, IgM, and IgG4 became apparent in five of the six children with persistently low serum IgG2 values. This study demonstrates that subnormal serum concentrations of IgG2 may be associated with varied patterns of immunologic dysfunction, some of which are evolving and may be responsible for increased susceptibility of these children to infection.

Adolescent↗