Haemophilus influenzae type b conjugate vaccines

Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children worldwide. During childhood, acquisition of antibody directed against the polysaccharide capsule of the organism, presumably as a result of asymptomatic carriage, confers protection and disease is much less common after the age of 4 years. Like other polysaccharides, the polyribosyl ribitol phosphate (PRP) of the Hib capsule is a T-independent antigen and not immunogenic when administered as a vaccine in infancy. Because the highest rates of disease occur in the first 2 years of life, efficacious Hib vaccines have been designed by covalently linking the PRP capsule to a carrier protein that recruits T-cell help for the polysaccharide immune response and induces anti-PRP antibody production even in the first 6 months of life. Introduction of Hib protein-polysaccharide conjugate vaccines into many industrialized countries over the past 15 years has resulted in the virtual elimination of invasive Hib disease. However, despite the success of the vaccine programme several factors may interfere with the effectiveness of the vaccine in the routine programme, as observed in the UK recently. Such factors may include interference with other concomitant vaccines, waning immunity in the absence of booster doses of vaccine, and reduced natural boosting as a result of decreased transmission of the organism. However, the burden of disease remains highest in resource-poor countries and urgent efforts are needed to provide the benefits of this vaccine for children living in regions where it cannot be used for economic and logistical reasons.     

The acquisition of anti-pneumococcal capsular polysaccharide Haemophilus influenzae type b and tetanus toxoid antibodies, with age, in the UK.

Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and to tetanus toxoid (TT), were measured in serum samples of 750 age-stratified subjects from the UK. The study subjects comprised healthy adult volunteers and hospitalized children undergoing elective surgery, excluding those with a history of infection or under investigation for immunological or haematological disorders. These antibody levels were calibrated by comparison with serum pool obtained from healthy adult volunteers, who were immunized with Hib polyribose-phosphate vaccine (Merieux). The data are intended to provide reference ranges to assist in the interpretation of specific antibody measurements in the clinical setting. Maternal IgG pneumococcal capsular polysaccharide (PCP) specific antibody levels, geometric-mean titre (GMT) 1/22, were lost by 6 months of age (GMT of 1/9). They remained low until 3-5 years (GMT of 1/20), and consisted principally of IgG1. Thereafter, IgG anti-PCP antibody titres increased steadily to adult levels (GMT of 1/275), of which 80% was IgG2. Anti-PCP antibody titres of the IgM isotype rose steadily from a GMT 1/21 (0-6 months) to 1/420 (3-5 years), a level which was maintained until adulthood. Anti-Hib antibody concentrations, determined by RABA, again demonstrated the decline in maternal antibody, from 0.18 micrograms/ml in the 0-6 month age cohort, to 0.09 microgram/ml between 6 and 12 months. Geometric-mean antibody concentrations remained below 0.2 micrograms/ml until 3-5 years, then increased with age, attaining the mean adult level of 1.02 micrograms/ml. Anti-TT antibody concentrations were measured in the same sera, by ELISA. Two peaks in anti-TT antibody levels were seen in children of 0.059 IU/ml and 0.166 IU/ml corresponding to the schedule of routine childhood immunization in the first year and at 5 years of age.     

Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection

Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8–69 months and 15 carefully age-matched healthy controls once with a Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG 1–4 specificity were determined by ELISA. There were no significant differences between the two groups in any single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls ( P = 0.036). Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls ( P = 0.005), whereas 1 month later they had significantly more IgM antibody (P = 0.038). No other significant differences were found between the groups before or after immunization with respect to antipolysaccharide Hib antibodies. Since naturally occurring IgG antibodies are thought to be aquired partly as a consequence of antigenic stimulation on mucosal surfaces, we hypothesize that the low level of specific IgG found before immunization, as well as the low total IgG in the children with RLRI, may reflect an impaired ability to prime through mucosal surfaces. This is supported by our finding of an increased IgM response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory. In conclusion, children with RLRI can be protected against invasive Hib infection as well as healthy children, but may have an immunodeficiency characterized by defective ability to respond to antigenic stimulation on mucosal surfaces.     

b型流感嗜血杆菌D蛋白原核可溶性表达研究

目的 通过原核表达系统可溶性表达重组D蛋白,为多糖结合疫苗的制备提供蛋白载体.方法 将Hib CMCC株基因组DNA中去除信号肽的hpd基因片段插入pET43.1a表达质粒,转化入感受态大肠埃希菌BL21 (DE3),IPTG诱导表达.表达的重组蛋白,经过硫酸铵沉淀和DEAE阴离子交换柱层析纯化后,用Western Blot的方法鉴定其免疫反应原性.结果 表达的重组蛋白以可溶性形式存在,表达量约占菌株总蛋白的44％,经过初步纯化后的重组蛋白可以和Hib抗血清发生特异性反应.结论 成功构建了D蛋白重组表达质粒,并在原核细胞中以可溶性形式表达出具有良好免疫反应原性的D蛋白.     

Expression of Haemophilus influenzae type b idiotype 1 on naturally acquired antibodies

The Chinese population in Hong Kong has a low incidence of invasive Haemophilus influenzae type b (Hib) disease, as well as carriage of the microorganism. Likely stimuli for the natural antibodies to Hib, which might protect against Hib infection, are cross-reactive antigens of bacteria like Escherichia coli K100. Our aim was to determine the isotype and idiotype distribution and cross-reactivity of natural antibodies against Hib capsular polysaccharide (CP) in healthy Hong Kong Chinese. Titration of 20 sera by ELISA showed IgG antibodies reacting with Hib CP in all individuals. The antibodies were mainly IgG2, and their avidity index ranged widely. Isoelectric focusing (IEF) combined with immunoblotting showed patterns of IgG2 antibody clones against the CP of Hib and E. coli K100 which were similar in 10 cases. Absorption with Hib CP only eliminated some bands in two sera. Absorption with K100 CP did not remove any anti-Hib CP bands. In three sera additional clones of antibodies reacting to K100 CP only, disappeared after absorption with this CP. Spectrotypic analyses of IgG antibodies reacting with anti-Hib idiotype 1 (Id-1) revealed stronger IEF patterns with bands in differing locations compared with anti-Hib CP antibodies. The strong reactivity of serum IgG, IgA and IgM antibodies with monoclonal anti-Hib Id-1 was confirmed by ELISA. This reactivity was not abolished after absorption of the sera with either Hib CP, or K100 CP. The data indicate a high prevalence of Id-1 among Hong Kong Chinese. However, only one individual had Id-1 antibodies specific for Hib CP, judging from absorption experiments. Others had much lower activity of Id-1 anti-Hib CP antibodies compared with the total IgG Id-1, suggesting that Hong Kong subjects have Id-1-positive antibodies in their serum which are not specific for Hib CP. This is consistent with the nature of Id-1, which is a marker of A2V_L region usage rather than a marker of a Hib CP paratope. We suggest that natural antibodies reacting with Hib CP in healthy Hong Kong Chinese are the product of exposure to some cross-reactive antigen(s), different from both Hib and E. coli K100 CP.     

几株b型流感嗜血杆菌多糖结合物的免疫原性检定

目的 从分子水平检定b型流感嗜血杆菌,研究不同菌株荚膜多糖结合物的免疫原性.方法 提取基因组,通过型特异和荚膜型基因特异引物,利用PCR检定b型流感嗜血杆菌;不同纯化多糖分别与破伤风类毒素(TT)进行耦联结合,结合物原液经稀释免疫小鼠,通过两针免疫,采血进行免疫效力测定.结果 5株b型流感嗜血杆菌通过PCR法均能获得预期大小的型特异(482 bp)和荚膜型(343 bp)基因片段,BLAST分析显示,各菌之间型特异和荚膜型序列比对,其同源性均为100％,各菌型特异和荚膜型序列分别与GenBank X78559.1和M19995.1序列比对,同源性分别为99％和100％;ELISA检测显示,4株不同菌株来源的荚膜多糖结合物(PRP-TT)的小鼠免疫效力差异无统计学意义.结论 通过PCR法从分子水平检定b型流感嗜血杆菌,纯化的不同荚膜多糖结合物小鼠免疫原性基本一致.可供不同Hib多糖结合物免疫原性的研究参考数据.     

Haemophilus influenzae type b opsonins of intravenous immunoglobulins

Immunoglobulin G may be prepared by different methods for intravenous infusion and administered as replacement therapy for hypogammaglobulinemia. Intravenous immunoglobulins prepared by different methods were comparedin vitro for their ability to opsonizeHaemophilus influenzae type b in the absence of complement and subsequently induce neutrophil chemiluminescence. While the antibody contents, measured by an enzyme-linked immunosorbent assay and radioimmunoassay, were equivalent, the immunoglobulin prepared by a non-molecular modifying method (ion-exchange chromatography) had the greatest ability to induce bacterial-neutrophil interaction, measured by chemiluminescence, while a reduced and alkylated immunolgobulin had the least. Thus, preparative methods may have a profound effect upon the function of intravenous immunoglobulins. The biological function of immunoglobulins for clinical use can be compared easily by neutrophil chemiluminescence.     

Correlation of serum immunoglobulin subclass concentrations with antibody responses of children to immunization withHaemophilus influenzae type b polysaccharide-pertussis vaccine

Children less than 24 months of age respond poorly to immunization with the capsular polysaccharide ofHaemophilus influenzae type b. Because human antibodies to polysaccharide antigens are relatively restricted to IgG₂, a late-maturing subclass, we examined the relationship between serum subclass concentrations and anticapsular antibody responses of 41 healthy children, 9 to 38 months of age, following immunization with type b polysaccharide mixed with pertussis vaccine. Both total and IgG anticapsular antibody responses correlated significantly with preimmune serum concentrations of IgG₂ but not with those if IgG₁. This correlation was age dependent, however, and after the effect of age was removed by partial correlation, the correlation between anticapsular antibody responses and serum IgG₂ concentrations was no longer significant. These findings indicate that the ability to respond to this vaccine coincides with maturation of the ability to secrete immunoglobulin of the IgG₂ subclass; however, individual variation in IgG₂ that is independent of age does not correlate with antibody response to the type b polysaccharide.     

Subclasses of IgA antibodies in serum and saliva samples of newborns and infants immunized against rotavirus

Little is known about subclass levels of IgA in serum or saliva of infants in the perinatal period. We have previously shown that very young infants are capable of responding to an experimental rotavirus vaccine with both serum and salivary IgA, and that small amounts of IgA are already detectable in cord blood of these infants. In the present study, total IgA1 and IgA2 antibodies in serum and saliva samples of some of these infants at birth, at 6 weeks of age, and at 12 weeks of age, were determined by a quantitative ELISA. Also, subclass-specific IgA antibodies to the rotavirus group A common antigen were determined by ELISA. The ratio of average serum concentrations of IgA1 to IgA2 for 14 infants at 6 weeks of age was 19:1, while in saliva it was 5:1. Between 6 and 12 weeks of age levels of serum IgA1 increased by 25%, while levels of IgA2 did not increase perceptibly. Concentrations of IgA1 were higher in infant sera than in saliva, while concentrations of IgA2 were slightly higher in saliva than in serum. When calculated as specific ELISA units per mg IgA1, more salivary IgA1 was specific for rotavirus than serum IgA1. Further studies are needed to determine when infant IgA2 levels rise to values more characteristic of children and adults. This may be of significance for infant mucosal immunizations if secretory IgA2, more resistant to bacterial proteases than IgA1, is required for efficient defence of the respiratory and intestinal tracts.     

Multi locus sequence type comparison of invasive and commensal Haemophilus influenzae isolates from Delhi

Haemophilus influenzae is a major public health concern in the developing world. The most virulent strain is H. influenzae Type b (Hib). Hib also constitutes a major portion of nasopharyngeal commensal flora in otherwise healthy individuals. Through dendogram based on composite gene sequences of seven multi locus sequence type genes, it was observed that invasive and commensal isolates made two completely separate clusters which are indicative of independent evolution of these two groups of H. influenzae in the Indian subcontinent.     

Cost-benefit analysis of haemophilus influenzae type B immunization in Korea

An economic evaluation of Haemophilus influenzae type b (Hib) immunization was conducted to examine whether Hib immunization should be included in Korea's national immunization program. The costs and benefits included direct and indirect values and an estimation of the economic efficiency. We determined that a universal Hib immunization program in Korea would prevent 17 deaths and 280 invasive Hib cases. When we assumed the one Hib immunization cost as 26,000 won, the national Hib immunization would cost 34.6 billion won. Costs for various Hib diseases were estimated at 26.8 billion won (11.8 billion won from direct costs and 14.9 billion won from indirect costs). A benefit-cost ratio of 0.77 showed that the economic efficiency of the integration of Hib immunization in Korea is low because of the low incidence rate of Hib disease and high price of vaccine. However, if the Hib immunization cost decrease to less than 20,000 won, a benefit-cost ratio increase to 1.0 and above, integrating Hib immunization into the national immunization program with economic efficiency can be considered.     

Bacteroides gingivalis-specific serum IgG and IgA subclass antibodies in periodontal diseases

The level of serum IgM, IgG and IgA antibodies including IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2 subclass-specific antibodies to Bacteroides (Porphyromonas) gingivalis fimbriae and to lipopolysaccharide (LPS) were analysed in patients with different forms of periodontal disease (PD) and control subjects by ELISA. Among PD subjects, sera obtained from adult periodontitis (AP), rapidly progressive periodontitis (RPP) and gingivitis contained high titres of fimbriae-specific IgG antibodies (7500-15,000 ELISA units) followed by IgA (90-700 units) and IgM (30-90 units). In contrast, sera from localized juvenile periodontitis (LJP) subjects exhibited much lower titres of fimbriae-specific IgG (89 +/- 11 units), IgA (31 +/- 5 units) and IgM (17 +/- 3 units) antibodies. A similar response pattern was also seen in sera from normal subjects aged 35-41 years who practice normal oral hygiene, while sera of younger adults (aged 18-24) with superior hygiene did not have any antigen-specific antibodies. Analysis of IgG subclass anti-fimbriae responses revealed that the major response was IgG3 followed by IgG1, IgG2 and IgG4 in AP, RPP and gingivitis. Although lower, a similar pattern of IgG subclass titre was seen in LJP and normal subjects aged 35-41 years. When IgA subclass responses were measured in AP and RPP, higher titres of the fimbriae-specific response were noted with IgA1 when compared with IgA2. However, lower but approximately equal levels of fimbriae-specific IgA1 and IgA2 titres were seen in other PD groups. When anti-B. gingivalis LPS-specific responses were measured, the sera of AP patients contained high levels of IgG antibodies (2265 +/- 224 units) followed by IgA (411 +/- 90 units) and IgM (214 +/- 56 units). Further, IgG anti-LPS responses were mainly IgG2 followed by IgG4, IgG3 and IgG1. For IgA subclass responses, higher titres of anti-LPS-specific antibodies were noted in IgA2 subclass over IgA1. These results showed that higher anti-B. gingivalis antibody responses occur in PD when compared with healthy individuals and protein and lipid-carbohydrate antigens of B. gingivalis induce distinct patterns of antigen-specific IgG and IgA subclass responses.     

Immunization with Haemophilus influenzae Type b Conjugate Vaccine in Children Given Bone Marrow Transplantation: Comparison with Healthy Age-Matched Controls

Forty-seven patients (age range, 7 months–18 years)with malignant (38 cases) and nonmalignant (9 cases)disorders given an allogeneic or an autologous bone marrowtransplantation (BMT) were immunized with Haemophilusinfluenzae type b (Hib) polysaccharide–diphtheriatoxoid conjugate vaccine administered in a single dose at different timepoints after transplantation. Results were compared with those of 13healthy children matched for age and sex who received the sameimmunization schedule. Serum and saliva samples for measurement of totalIgG subclass and specific antibody levels were obtained from patientsand healthy controls before and 3 weeks after vaccination. Twenty-fiveof the 47 patients (53%) had a specific anti-Hib IgGresponse, while an effective IgA and IgM response was mounted by 23(49%) and 11 (23%) children,respectively. In the control group, 13 of 13 subjects mounted a specificIgG antibody production (P < 0.005 in comparison to thepatients' response rate), while an IgA and IgM response wasdemonstrated in 12 (92%; P < 0.01compared to transplanted patients) and 7 (54%;P < 0.05 in comparison to BMT recipients) children,respectively. Lapse of time from BMT to immunization was the mostimportant factor predicting antibody response, as proved by an effectiveincrease in prevaccination specific IgG levels in the majority ofpatients vaccinated after 2 years from transplant. Our data demonstratethat BMT recipients have a reduced capacity to mount an antibodyresponse to polysaccharide antigens compared to normal controls, evenwhen a protein-conjugated vaccine is employed. Since time aftertransplant is the major factor influencing the recovery of immunereactivity to polysaccharide antigens, the ontogeny of the B cellrepertoire seems to follow a predetermined sequential program ofdevelopment.     

Simultaneous single-tube PCR assay for the detection of Neisseria meningitidis, Haemophilus influenzae type b and Streptococcus pneumoniae

Rapid, accurate and inexpensive diagnosis of bacterial meningitis is critical for patient management. This study describes the development and evaluation of a multiplex PCR assay for the detection of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b, which globally account for 90% of cases of bacterial meningitis. The single-tube assay, based on the ctrA, ply and bex targets, respectively, enabled detection of 5-10 pg DNA. When the assay was tested with clinical samples (n = 425), its sensitivity for the three targets was 93.9%, 92.3% and 88%, respectively, while the overall specificity and positive predictive value of the assay was 100%. The negative predictive value was 99.1-99.5%. The methodology permits rapid and accurate detection of the three main pathogens that cause bacterial meningitis.     

Both IgA subclasses are reduced in parotid saliva from patients with AIDS

Secretory IgA (SIgA), the isotypes IgA1 and IgA2, and IgM were measured by ELISA in stimulated parotid saliva from patients with AIDS (n = 16), subjects with asymptomatic HIV infection (n = 28), and HIV-seronegative healthy controls (n = 19). SIgA was significantly reduced in the AIDS group (10.4 micrograms/ml) compared with the asymptomatic HIV-infected subjects (17.1 micrograms/ml) and the controls (23.0 micrograms/ml). This decrease comprised both IgA1 and IgA2 to a similar extent on a relative basis. The SIgA decrease in AIDS patients was in striking contrast to their serum IgA level, which was significantly increased (6.9 g/l) compared with the asymptomatic HIV-infected subjects (2.9 g/l) as well as the controls (2.8 g/l). Low parotid output of SIgA in patients with HIV infection was associated with low numbers of CD4+ lymphocytes in peripheral blood as well as the presence of oral infections. The parotid output of IgM was similar in all groups. A low level of SIgA in the external secretions of patients with AIDS may well contribute to their frequent mucosal infections of opportunistic microorganisms.     

Clinical characteristics of Haemophilus influenzae meningitis in Denmark in the post-vaccination era

The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nation-wide registration, clinical information and laboratory findings were collected from all 65 confirmed cases of H. influenzae meningitis during the period 1994–2005. Twenty-nine patients (45%) were <13 years old [median 15 months (range 0–147)], and 36 patients (55%) were >24 years old [median 62 years (range 25–96)]. Hib accounted for 31% (20/65) of the cases, and significantly more children were infected with Hib compared with adults [53% (16/29) vs. 11% (4/36), respectively, p 0.0003]. Overall, 38% of cases had an otogenic focus and this was thus the most frequent primary focus of infection. Among children infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83–96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults. The presence of a lung focus was an independent prognostic factor for an unfavourable outcome (p 0.03). In conclusion, meningitis caused by Hib has been infrequent in Denmark after introduction of the Hib vaccine in the childhood vaccination programme, and no increase in meningitis cases due to non-b type H. influenzae has been observed. Cases with H. influenzae meningitis frequently had an otogenic focus, with low risk of an unfavourable outcome.     

Antibiotic susceptibilities of Haemophilus influenzae in central Scotland

Objective: To ascertain the incidence of antibiotic resistance in Haemophilus influenzae in central Scotland and the β-lactamases produced by these isolates.
Methods: A total of 213 H. influenzae isolates from four medical centers in Scotland [Aberdeen ( n = 58), Edinburgh ( n = 55), Glasgow ( n = 64) and Dundee ( n = 36)] were tested for susceptibility to a range of antimicrobials including β-lactams, β-lactam/β-lactamase-inhibitor combinations, and a representative 4-quinolone, antifolate and macrolide. Susceptibility testing of the β-lactam/β-lactamase-inhibitor combination amoxicillin plus clavulanic acid was conducted at both 2:1 and 4:1 ratios and with clavulanic acid fixed at a concentration of 2 mg/L. Each strain was further investigated for the presence of β-lactamase activity.
Results: Although the incidence of resistance to amoxicillin was 15%, in the presence of clavulanic acid, this resistance was reduced to 4.2%, 5.6% and 4.2% with the 2:1 ratio, 4:1 ratio and 2 mg/L fixed concentration, respectively. Sixteen percent of the isolates demonstrated immediate β-lactamase production. Isoelectric focusing showed that 77.4%, 16.1% and 6.5% of the β-lactamase-positive strains were found to contain TEM-1, VAT-1 and both TEM-1 and VAT-1 β-lactamases, respectively. A further 29% of the strains were recognized as being β-lactamase-positive after prolonged incubation with nitrocephin.
Conclusions: This study suggests that current testing for β-lactamases may underestimate the prevalence of β-lactamase production in H. influenzae.     

Porphyromonas gingivalis-specific serum IgG and IgA antibodies originate from immunoglobulin-secreting cells in inflamed gingiva.

Patients with adult periodontitis (AP) exhibit elevated serum antibody levels to Porphyromonas (Bacteroides) gingivalis; however, it is not known whether these antibodies originate from plasma cells in the local disease site or from peripheral lymphoid tissues. We studied the isotype and subclass levels and origin of antibodies to P. gingivalis fimbriae, since elevated serum anti-fimbriae responses were seen when compared with sera of healthy controls. IgG anti-fibriae titres were dominant and the subclass response was IgG3 much greater than IgG1 greater than IgG2 much greater than IgG4; however, some IgA anti-fimbriae antibodies were also seen. The IgA subclass fimbriae-specific response was mainly IgA1; however, significant IgA2 anti-fimbrae antibodies were seen. We also assessed numbers of anti-fimbriae antibody producing cells from peripheral blood mononuclear cells (PMBC) and from either healthy or inflamed gingiva of AP subjects. Gingival mononuclear cells (GMC) of AP patients exhibited high numbers of immunoglobulin-producing (spot-forming) cells (SFC) including fimbriae-specific antibody secreting cells in a pattern of IgG greater than IgA greater than greater than greater than IgM. However, low numbers of SFC were seen in GMC from healthy gingiva; further, no anti-fimbriae SFC responses were noted in healthy GMC. Although no fimbriae-specific immunoglobulin-producing cells were seen in PBMC, low numbers of antigen-specific SFC were found in pokeweed mitogen-triggered PBMC from AP subjects. Treatment of AP patients for plaque and surgical removal of inflamed gingiva resulted in significant reductions in serum anti-fimbriae responses. These studies show that AP patients exhibit brisk serum IgG and IgA subclass anti-fimbriae antibodies, whose origin appear to be the plasma cells present in the localized inflamed tissues.     

Immunogenicity of Haemophilus influenzae Type b Conjugate Vaccines in Korean Infants: A Meta-analysis

A meta-analysis was performed on the immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines after 2 (2 and 4 months) and 3 doses (2, 4, and 6 months) in Korean infants. A database search of MEDLINE, KoreaMed, and Korean Medical Database was done. The primary outcome measure was the proportion of infants with anti-polyribosylribitol phosphate (PRP) concentrations ≥1.0 µg/mL. Eight studies including eleven trials were retrieved. One trial reported on the diphtheria toxoid conjugate vaccine (PRP-D) and 2 trials each on the mutant diphtheria toxin (PRP-CRM) and Neisseria meningitidis outer-membrane protein (PRP-OMP) conjugate vaccine. Heterogeneity in study designs between trials on PRP-CRM was noted and one trial reported on a monovalent and another on a combination PRP-OMP vaccine. Thus, a meta-analysis was conducted only on the tetanus toxoid conjugate vaccine (PRP-T). After a primary series of 2 doses and 3 doses, 80.6% (95% confidence interval [CI]; 76.0-85.1%) and 95.7% (95% CI; 94.0-98.0%) of infants achieved an antibody level ≥1.0 µg/mL, respectively. The immunogenic response to the PRP-T vaccine was acceptable after a primary series of 3 doses and also 2 doses. A reduced number of doses as a primary series could be carefully considered in Korean infants.