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D M Granoff

Publications and source records attributed to D M Granoff.

At least 37 records · Page 2Linked to original sources
PubMed1998

Modulation of the immune system by human milk and infant formula containing nucleotides.

OBJECTIVE: To determine whether human milk and nucleotides added to infant formula at levels present in human milk enhance development of the immune system during infancy. METHODS: A 12-month, controlled, randomized and blinded, multisite feeding trial was conducted on two infant formulas: iron-fortified, milk-based control formula (Control) or the same formula fortified with nucleotides (Nucleotide). The level (72 mg/L) and ratio of individual nucleotides selected were patterned after those available in human milk. A third group fed human milk exclusively for 2 months and then human milk or Similac with iron until 12 months of age also was studied. Response to immunizations was chosen to assess development of the immune system. Infants followed the immunization schedule recommended by the American Academy of Pediatrics in 1991. OUTCOME VARIABLES: Antibody responses were determined at 6, 7, and 12 months of age to Haemophilus influenzae type b polysaccharide (Hib), to diphtheria and tetanus toxoids, and to oral polio virus (OPV) immunizations. RESULTS: Of 370 full-term, healthy infants enrolled, 311 completed the study (107 Control, 101 Nucleotide, 103 human milk/Similac with iron). Intake, tolerance, and growth of infants were similar in all three groups. Compared with the Control group 1 month after the third immunization (7 months of age), the Nucleotide group had a significantly higher Hib antibody concentration (geometric mean concentrations of 7.24 vs 4.05 micrograms/mL, respectively), and a significantly higher diphtheria antibody concentration (geometric mean of 1.77 vs 1.38 U/mL). The significantly higher Hib antibody response in the Nucleotide group persisted at 12 months. The antibody responses to tetanus and OPV were not enhanced by nucleotide fortification. There also was an effect of breastfeeding on immune response. Infants who breastfed had significantly higher neutralizing antibody titers to polio virus than either formula-fed group (1:346 vs 1:169 and 1:192 in the Control and Nucleotide groups, respectively) at 6 months of age. CONCLUSION: Infant formula fortified with nucleotides enhanced H influenzae type b and diphtheria humoral antibody responses. Feeding human milk enhanced antibody responses to OPV. Dietary factors play a role in the antibody response of infants to immunization.

Bottle Feeding↗
PubMed1997

Factors associated with superior antibody responses to a single dose of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine administered to Chilean infants at 2 months of age.

The anticapsular antibody response of Chilean infants to a single dose of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate, vaccine is substantially higher than that observed among infants of similar age from the USA. Comparison of selected demographic and environmental factors indicates that low maternal education and a greater number of persons in the home are significantly associated with the superior responder phenotype. High anticapsular antibody responses were associated with high antibody responses to tetanus toxoid, the carrier protein in this conjugate, but not to diphtheria toxoid. These data suggest that environmental factors may enhance the magnitude of the primary antibody response to PRP-T vaccine.

Antibodies, Bacterial↗
PubMed1997

Phase I study of the immunogenicity and safety of conjugated Hemophilus influenzae type b vaccines in the elderly.

In infants, vaccines consisting of a carrier protein conjugated to the bacterial capsular polysaccharide (PRP) are far more protective against Hemophilus influenzae type b (Hib) disease than unconjugated PRP. To determine the tolerability and immunogenicity of Hib conjugate vaccines in the elderly, we vaccinated 30 volunteers, aged 69-84 years, with either PRP conjugated to an outer membrane protein complex (PRP-OMP), or PRP oligomers conjugated to CRM197, a nontoxic, mutant diphtheria toxin (HbOC). Prior to vaccination, 40% of subjects had serum anti-PRP antibody levels < 1.0 microgram ml-1. Four weeks following vaccination, all subjects had concentrations > 1.0 microgram ml-1, a level generally considered to be protective. The post-vaccination geometric mean concentrations were 35.5 and 50.1 micrograms ml-1 for the PRP-OMP and HbOC groups, respectively (0.05 < P < 0.10). Subjects in the HbOC group, but not the PRP-OMP group, showed, on average, ten fold increases in IgG antibody to diphtheria toxoid after conjugate vaccination. Side-effects of vaccination were mild except in one subject given HbOC, who developed extensive erythema and swelling of the injected arm.

Aged↗
PubMed1997

Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine.

Two hundred twenty-one Gambian children vaccinated previously with one, two, or three doses of a meningococcal conjugate vaccine or two doses of polysaccharide vaccine before the age of 6 months were revaccinated at the age of 18-24 months with either meningococcal polysaccharide, conjugate, or inactivated polio vaccines. Children who had previously received one, two, or three doses of conjugate vaccine had significantly (P < .001) higher anti-group C meningococcal antibody levels following revaccination than did children vaccinated with a polysaccharide vaccine for the first time. Children vaccinated previously with two doses of polysaccharide vaccine had a lower group C antibody response than did control children. Group A antibody responses following revaccination of children who had previously received polysaccharide or conjugate vaccine were not significantly higher than those in control children. Thus, immunologic memory was probably induced by the group C but not by the group A component of the conjugate vaccine.

Antibodies, Bacterial↗
PubMed1997

Safety and immunogenicity of Chiron/Biocine recombinant acellular pertussis-diphtheria-tetanus vaccine in infants and toddlers.

OBJECTIVE: To evaluate the safety and immunogenicity of the recombinant acellular pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine). STUDY DESIGN: This is a randomized blinded trial evaluating the safety and immunogenicity of the recombinant aPDT vaccine (C-aPDT, Chiron/Biocine) in 2000 infant recipients compared with 498 controls who received whole cell diphtheria-pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated as a booster dose in a subset of the same population when given at 15 to 18 months of age and compared with licensed Lederle aPDT vaccine. RESULTS: The C-aPDT vaccine was associated with very few local or systemic reactions when compared with wDPT. In toddlers the local and systemic side effects observed were similar after either acellular vaccine. When the immunogenicity of the C-aPDT vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus response and the C-aPDT vaccine was significantly more immunogenic for all other antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or improved immunogenicity for antigens tested as compared with Lederle aPDT except for a higher anti-filamentous hemagglutinin response with the Lederle aPDT vaccine. CONCLUSION: The Chiron/Biocine aPDT vaccine offers an improved safety profile as well as improved immunogenicity when compared with a licensed wDPT product.

Antibodies, Bacterial↗
PubMed1997

Oligoclonality of serum immunoglobulin G antibody responses to Streptococcus pneumoniae capsular polysaccharide serotypes 6B, 14, and 23F.

Serum antibodies (Abs) specific for the capsular polysaccharides of Streptococcus pneumoniae provide protection against invasive pneumococcal disease. Previous studies indicate that Abs to pneumococcal polysaccharide (PPS) serotypes 1 and 6B have limited clonal diversity. To determine if restricted diversity was a feature common to other PPS specificities, we examined the light (L)-chain expression and isoelectric heterogeneity of type 6B, 14, and 23F Abs elicited in 15 adults following PPS vaccination. At the population level, both PPS-6B and PPS-14 Abs expressed kappa and lambda chains, although 6B Abs more frequently expressed lambda chains lambda and 14 Abs more frequently expressed kappa chains. In individual sera, Abs were generally skewed towards either kappa or lambda expression. 23F-specific Abs had predominantly kappa chains. Isoelectric focusing analyses showed that sera contained one or at most a few immunoglobulin G Ab spectrotypes to all three respective capsular serotypes, a result indicative of oligoclonality. A sequence analysis of a purified PPS-14-specific Ab having a single spectrotype gave uniform amino-terminal sequences for both the heavy chain (V(H)III subgroup) and the L chain (kappaIII-A27 V region). From these results we conclude that within individual adults, serum Ab responses to PPS serotypes 6B, 14, and 23F derive from a small number of dominant B-cell clones, and consequently variable-region expression is probably individually limited as well. Oligoclonality appears to be a general characteristic of human PPS-specific Ab repertoires, and we suggest that this property could lead to individual differences in Ab fine specificity and/or functional activity against encapsulated pneumococci.

Adolescent↗
PubMed1997

MF59 adjuvant enhances antibody responses of infant baboons immunized with Haemophilus influenzae type b and Neisseria meningitidis group C oligosaccharide-CRM197 conjugate vaccine.

The ability of the adjuvant MF59 to enhance the immunogenicity of polysaccharide-protein conjugate vaccines was investigated in infant baboons. MF59 consists of stable droplets (<250 nm) of the metabolizable oil squalene and two surfactants, polyoxyethylene sorbitan monooleate and sorbitan trioleate, in an oil-in-water emulsion. In humans, MF59 is well tolerated and enhances the immunogenicity of recombinant protein subunit or particle vaccines. Its effect on the immunogenicity of polysaccharide-protein conjugate vaccines is unknown. Baboons 1 to 4 months of age were immunized intramuscularly with Neisseria meningitidis group C and Haemophilus influenzae type b (Hib) oligosaccharide-CRM197 conjugate vaccines. The lyophilized vaccines were reconstituted with phosphate-buffered saline (PBS), Al(OH)3 (alum), or MF59. Groups of five animals each were given three injections of the respective formulations, with one injection every 4 weeks. Four weeks after each immunization, the MF59 group had up to 7-fold-higher geometric mean anticapsular-antibody titers than the alum group and 5- to 10-fold-higher N. meningitidis group C bactericidal-antibody titers. Twenty-one weeks after the third immunization, the MF59 group still showed 5- to 10-fold-higher anticapsular-antibody titers. The antibody responses of the animals given the vaccines reconstituted with PBS were low at all times measured. Both the MF59 and alum groups, but not the PBS group, showed booster antibody responses to unconjugated Hib and N. meningitidis group C polysaccharides, results consistent with induction of memory B cells. Thus, MF59 may be useful for accelerating and augmenting immunity to polysaccharide-protein conjugate vaccines in infants.

Alum Compounds↗
PubMed1997

Are serological responses to acellular pertussis antigens sufficient criteria to ensure that new combination vaccines are effective for prevention of disease?

Combining several vaccines in a single formulation can alleviate the increasing complexity of the paediatric vaccination schedule. However, vaccine antigens that are highly effective when administered singly may lose potency in combination; consequently, the efficacy of each component must be established for any new proposed combination vaccine. When the serological response to a vaccine correlates clearly with clinical efficacy, the efficacy of that component in a combination can be inferred from immunogenicity studies. Poliovirus, tetanus and diphtheria toxoids, Haemophilus influenzae type b and Neisseria meningitidis, and hepatitis B vaccines, can all be assessed in this manner. Unfortunately, the antibody titres induced by acellular pertussis vaccines do not correlate with vaccine efficacy. Thus, although diphtheria-tetanus-acellular pertussis (DTaP) vaccine has been considered a prime building block in the development of new combination vaccines, modifying DTaP by the addition of new vaccine components may decrease the ability of the vaccine to protect against pertussis without a change in serum antibody response. For this reason, immunogenicity is not an adequate or safe basis for licensing combination vaccines containing acellular pertussis. Development and licensing of new combination vaccines containing components with serological correlates of clinical efficacy can proceed more rapidly than DTaP-based combinations and should be pursued.

Antibodies, Bacterial↗
PubMed1995

Laboratory correlates of protection against Haemophilus influenzae type b disease. Importance of assessment of antibody avidity and immunologic memory.

The concentration of serum antibody to the Haemophilus influenzae type b polysaccharide sufficient to confer protection against Hib disease has been estimated to range from 0.15 to 1.0 microgram/ml as measured by conventional antigen binding assays. However, the ability of these serologic tests to predict vaccine equivalence and/or protective efficacy is limited since there are important qualitative differences in vaccine-induced anti-PRP antibody, such as isotype, variable region usage, and antibody avidity. These differences may profoundly affect the biologic activity of the antibody. Also, Hib conjugate vaccination primes infants for memory antibody responses to a subsequent encounter with PRP, and immunologic priming can occur in infants with very low serum anti-PRP antibody responses to conjugate vaccination, or in those whose antibody concentrations have declined after vaccination. Primed infants are likely to be protected against Hib disease in the absence of "protective" serum antibody concentrations because priming permits a rapid serum anti-PRP antibody response upon encountering the organism. Thus, quantitative assessment of immunogenicity, by itself, is insufficient to predict vaccine equivalence or protective efficacy. In defining surrogate serologic tests for prediction of vaccine efficacy, assessments of antibody avidity and induction of immunologic memory should be included. Ideally, these assessments should be supplemented with antibody functional assays such as complement-mediated bactericidal activity, opsonic activity, or passive protection in animal models of disease.

Antibodies, Bacterial↗
PubMed1995

Functional differences in idiotypically defined IgG1 anti-polysaccharide antibodies elicited by vaccination with Haemophilus influenzae type B polysaccharide-protein conjugates.

We investigated the relationship between the form of the Haemophilus influenzae type B (Hib) polysaccharide (PS)-protein conjugate vaccine, Id expression, and Ab quality. Two post-vaccination pools were prepared from sera of infants vaccinated with either Hib PS oligomers coupled to CRM197, a mutant diphtheria toxin (HbOC), or with higher m.w. Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis group B (Hib-OMP). The mean anti-Hib PS Ab avidity of the serum pool from the infants vaccinated with HbOC was threefold higher than that of the pool from infants vaccinated with Hib-OMP. Using sequential immunoabsorption, three IgG1 idiotypically-defined anti-Hib PS fractions were isolated from each of the serum pools: Hibld-1, Hibld-2, and a Hibld-1/-2-depleted population, designated Hibld-0. Hibld-1 and Hibld-2 are idiotypic markers for anti-Hib PS Abs expressing kappa II-A2 and lambda VII V regions, respectively. Hibld-1 anti-Hib PS Abs had significantly higher avidity, 2- to 19-fold higher in vitro bactericidal activity, and were more protective against Hib bacteremia in infant rats, than the respective Hibld-2 Abs isolated from each of the pools. Comparing the two vaccines, Hibld-1 anti-Hib PS Abs elicited by HbOC had significantly higher avidity and 10-fold higher bactericidal and rat protective activity than the Hibld-1 Abs elicited by Hib-OMP. These findings demonstrate that the molecular form of the Hib PS immunogen dictates both V region usage and quality of Ab function.

Animals↗
PubMed1995

Complement-mediated bactericidal activity of human antibodies to poly alpha 2-->8 N-acetylneuraminic acid, the capsular polysaccharide of Neisseria meningitidis serogroup B.

Serum antibodies to Neisseria meningitidis group B (MenB) polysaccharide are reported not to elicit bacteriolysis in the presence of human complement. To reexamine this question, we evaluated the ability of two human IgM anti-MenB polysaccharide monoclonal antibodies (MAbs) and seven human MenB polysaccharide-reactive human IgM paraproteins to elicit bacteriolysis. In the presence of human complement, both MAbs and five of the seven paraproteins were bactericidal at antibody concentrations of 0.25-9.6 micrograms/mL (50% killing). Activity of the respective antibodies was enhanced 200- to > 10,000-fold when rabbit complement was used instead of human complement. With rabbit complement, the bactericidal activity of human IgM polyclonal antibody or MAb to Haemophilus influenzae type b (Hib) polysaccharide but not human IgG polyclonal antibody or MAb to Hib polysaccharide was similarly augmented. Thus, for both MenB and Hib, IgM antipolysaccharide antibodies elicit complement-mediated bactericidal activity in the presence of human complement, and the use of rabbit complement yields spuriously high activity.

Animals↗
PubMed1995

Antibody responses to the capsular polysaccharide of Neisseria meningitidis serogroup B in patients with meningococcal disease.

We measured antibody responses to meningococcal serogroup B (MenB) polysaccharide (PS) by enzyme-linked immunosorbent assay (ELISA) in sera from 94 patients from The Netherlands with disease caused by Neisseria meningitidis group B. The patients ranged in age from 3 to 73 years (mean age, 18.8 years). In initial studies we showed that the binding of a panel of MenB PS-reactive human immunoglobulin M (IgM) paraproteins to biotinylated MenB PS bound to avidin-coated microtiter wells was inhibited > 90% by the addition of soluble MenB PS or encapsulated group B meningococci. In contrast, inhibition of IgM anti-MenB PS antibody-binding activity in many of the patient sera was less than 50% (range, 20 to 94%). These data suggested a high frequency of nonspecific binding in the patient sera. Therefore, all serum samples were assayed in replicate in the presence or absence of soluble MenB PS, and only the inhibitable fraction of the binding signal was used to calculate the anti-MenB PS antibody concentrations. In 17 control patients with meningococcal disease caused by serogroup A or C strains, there was no significant difference in the respective IgM or IgG anti-MenB PS antibody concentrations in paired acute- and convalescent-phase sera. In contrast, in patients with MenB disease, the geometric mean IgM anti-MenB PS antibody concentration increased from 3.9 units/ml in acute-phase serum to 10.5 units/ml in convalescent-phase serum (P < 0.001). The corresponding geometric mean IgG anti-MenB PS antibody titers were 1:27 and 1:36 (P < 0.05). There was only a weak relationship between age and the magnitude of the logarithm of the antibody concentrations in convalescent-phase sera (for IgM, r2 = 0.06 and P < 0.05; for IgG, r2 = 0.08 and P < 0.01). Our data indicate that precautions are needed to avoid nonspecificity in measuring serum antibody responses to MenB PS by ELISA. Furthermore, although this PS is thought to be a poor immunogen, patients as young as 3 years of age recovering from MenB disease demonstrate both ImG and IgG antibody responses in serum.

Adolescent↗
PubMed1995

Human immunoglobulin M paraproteins cross-reactive with Neisseria meningitidis group B polysaccharide and fetal brain.

Three hundred fifty-nine serum samples from patients with immunoglobulin M (IgM) or IgG monoclonal gammopathies were tested for binding to the capsular polysaccharide (PS) of Neisseria meningitidis group B (MenB PS, poly-alpha[2-->8]-N-acetylneuraminic acid). Of 159 IgM paraproteins, 7 (4.4%) were positive, compared with 0 of 200 IgG paraproteins (P < 0.05). Since MenB PS reactivity was limited to the IgM paraproteins, the 159 IgM paraproteins were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with seven other bacterial PSs. None reacted with meningococcal A or C, Haemophilus influenzae type b, or Streptococcus pneumoniae type 3, 6, 14, or 23 PS. The specificity of the MenB PS-reactive antibodies was confirmed by demonstration of binding to N. meningitidis group B cells but not to a capsular PS-deficient mutant and by specific inhibition of binding to solid-phase MenB PS by soluble MenB PS in an ELISA. Five of five antibodies tested protected infant rats from bacteremia caused by Escherichia coli K1, an organism with a PS capsule that also is composed of poly-alpha[2-->8]-N-acetylneuraminic acid. Each of the seven MenB PS-reactive paraproteins had autoantibody activity as defined by binding to homogenates of calf brain in a radioimmunoassay. For six of the seven antibodies, binding to calf brain was inhibited by the addition of soluble MenB PS. Thus, approximately 4% of human IgM paraproteins have autoantibody activity to poly-alpha[2-->8]-N-acetylneuraminic acid, an antigen expressed in fetal brain and cross-reactive with the MenB capsular PS. The reason for this skewing of the IgM paraprotein repertoire toward reactivity with poly-alpha[2-->8]-N-acetylneuraminic acid antigenic determinants is unknown.

Animals↗
PubMed1994

Effect of carrier protein priming on antibody responses to Haemophilus influenzae type b conjugate vaccines in infants.

OBJECTIVE: To assess the effect of priming with diphtheria and tetanus toxoid vaccine (DT) at 1 month of age on the anticapsular polyribosylribitol phosphate (PRP) antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate (PRP-T) or PRP oligosaccharide-cross-reactive mutant diphtheria toxin conjugate (HbOC). DESIGN: Randomized controlled trial with serum samples assayed blindly. PARTICIPANTS AND SETTING: Healthy infants enrolled in private pediatric practices; 94 (91%) of 103 infants had prevaccination and postvaccination serum samples available for analysis. INTERVENTIONS: Two groups received DT vaccination at 1 month of age and subsequent injections of PRP-T or HbOC conjugate vaccines at 2, 4, and 6 months of age. The control groups were not vaccinated with DT but received PRP-T or HbOC at the same ages as the carrier-primed groups. Infants in all groups were given a booster injection of unconjugated PRP at 12 months of age to assess induction of immunologic memory. MAIN OUTCOME MEASURE: Concentrations of serum antibody to PRP. MAIN RESULTS: The DT-primed infants given PRP-T had twofold to threefold higher geometric mean anti-PRP antibody responses after one (P < or = .01), two (P < or = .01), or three (P = .06) doses of conjugate vaccine than the infants of the unprimed group. The primed infants also had threefold higher memory antibody responses to the booster PRP injection given at 12 months of age (concentration of 24.4 vs 8.4 micrograms/mL in infants not primed with DT; P < .01). The DT-primed infants given HbOC had twofold to threefold higher antibody responses after one (P = .07) or two (P < .01) doses of conjugate vaccine than the unprimed HbOC group, but there were no significant differences after the third dose of conjugate vaccine or after the PRP booster injection. CONCLUSIONS: Vaccination with DT at 1 month of age increases the magnitude of the anti-PRP antibody responses to conjugate vaccination. With HbOC, the effect of carrier priming was present for up to 6 months of age, whereas in infants vaccinated with PRP-T, enhanced immunity was present for at least 12 months.

Antibodies, Bacterial↗
PubMed1994

Variable region sequences and idiotypic expression of a protective human immunoglobulin M antibody to capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1.

We determined the heavy (H)- and light (L)-chain variable (V) region nucleotide and translated amino acid sequences of the human immunoglobulin M(kappa) monoclonal antibody (MAb) 5E1, which is specific for the polysaccharide capsule of Escherichia coli K1 and Neisseria meningitidis group B (poly[alpha(2-->8)-N-acetylneuraminic acid]) and which is protective in animal models of infection. The 5E1 VH gene is a member of the VHIIIb family and is 97% homologous to the 9.1 germ line gene. The 5E1 VL gene is a member of the kappa I subgroup and is 98% homologous to the germ line gene, 15A, also known as KLO12. The VL and/or VH genes used by 5E1 are highly homologous to the V genes encoding antibodies to the Haemophilus influenzae type b polysaccharide and to antibodies reactive with self-antigens such as erythrocyte "i," DNA, and thyroid peroxidase. We also produced three murine anti-idiotype (Id) MAbs against 5E1. All three anti-Ids recognize a minor subset of antimeningococcal B polysaccharide antibodies present in serum from normal adults. Two of the anti-Ids define distinct Ids associated with antibodies having kappa I-15A V regions. These 15A-associated Ids are expressed by some heterologous human antimeningococcal B polysaccharide MAbs, and they also are independently expressed by two human MAbs that are specific for either the H. influenzae b polysaccharide or the i erythrocyte antigen and that utilize the kappa I-15A V region. Taken together, these data indicate that the 5E1 antibody uses V regions that recur in the human antibody repertoires to this polysaccharide and to structurally dissimilar polysaccharides and autoantigens. Thus, the poor immunogenicity of poly[alpha(2-->8)-N-acetylneuraminic acid] cannot be explained by the unavailability of certain critical VH and VL genes required for generation of antibody response.

Amino Acid Sequence↗
PubMed1993

Age-dependent V region expression in the human antibody response to the Haemophilus influenzae type b polysaccharide.

The human L chain antibody repertoire specific for the Haemophilus influenzae type b (Hib) polysaccharide (PS) is composed of kappa I, kappa II, kappa III, kappa IV, and lambda L chain V regions, but the most commonly occurring VL is encoded by the unmutated V kappa II-A2 gene. To determine whether this VL repertoire is influenced by age, we used idiotypic probes to monitor V kappa II-A2, V lambda, and V kappa III usage in the antibody response to an Hib PS-protein conjugate vaccine. A single dose of a vaccine consisting of Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis was administered. Adults (n = 35), 18-month-old infants (n = 35), and 2-month-old infants (n = 46), all with > or = 0.9 microgram/ml anti-Hib PS antibodies, were tested for VL region markers in postvaccination sera. V kappa III anti-Hib PS antibodies were not detected in any of the 2-month-old infants but were detected in 29% of the 18-month-old infants and 69% of the adults (p < 0.001). The lack of kappa III antibodies in 2-month-old infants could not be accounted for by lack of a kappa response, because kappa antibodies to Hib PS were present (> 0.15 microgram/ml) in 45% of these infants. Hibld-1, an idiotope expressed by anti-Hib PS antibodies having the kappa II-A2 V region, was present in postvaccination sera of 66% of the adults and 80% of the 18-month-old infants but was less frequent in the 2-month-old infants (35%, p < 0.001). In contrast, Hibld-2, which is an idiotope expressed by a subset of V lambda VII anti-Hib PS antibodies, was rare or infrequent in adults and 18-month-old infants (0% and 6%, respectively) but was present in 43% of 2-month-old infants (p < 0.001). Our findings demonstrate that dramatic changes in VL region utilization occur in the human antibody response to this Hib PS conjugate vaccine as a function of age. Because previous studies have shown that V region usage correlates with antibody fine specificity and avidity for Hib PS, these age-related differences in V region expression may affect the ability of vaccines to confer protective immunity at different ages.

Adult↗
PubMed1993

Declining incidence of Haemophilus influenzae type b disease since introduction of vaccination.

OBJECTIVE: To determine the incidence of invasive Haemophilus influenzae type b disease in children living in Minnesota and Dallas County, Texas, before and since introduction of plain polysaccharide vaccine in 1985, and conjugate vaccine in 1988. Initially, use of these vaccines was limited to infants 18 months of age and older. DESIGN: Identification of culture-proven cases of H influenzae type b disease was through systems of active, laboratory-based surveillance. The mean incidence of disease (cases observed/100,000 child-years) for 1983 and 1984 served as a baseline for comparison with subsequent years through 1991. PARTICIPANTS: Children less than 5 years of age in Minnesota and Dallas County, Texas. Overall, there were 2557 confirmed age-eligible cases of invasive H influenzae type b disease from 1983 through 1991. RESULTS: Between the 1983-1984 baseline and 1991, the incidence of H influenzae type b disease decreased 85% in Minnesota and 92% in Dallas. Notably, declines in incidence were observed in children in the age group being vaccinated as well as in infants younger than 18 months of age prior to introduction of vaccination. CONCLUSION: In two widely separated areas of the United States, a profound decrease in the incidence of H influenzae type b disease has occurred. The data suggest that vaccination may be protecting against disease, as well as decreasing the spread of infection to unvaccinated infants.

Bacterial Capsules↗