Antibody persistence of two pentavalent DTwP–HB–Hib vaccines to the age of 15–18 months,and response to the booster dose of quadrivalent DTwP–Hib vaccine

Objectives

Antibody persistence in children following three doses of primary vaccination with diphtheria, tetanus, whole-cell-pertussis (DTwP), hepatitis B, and Haemophilus influenzae type b (Hib) vaccines (SIIL Pentavac vaccine vs. Easyfive^® of Panacea Biotec), and response to the booster dose of DTwP–Hib (Quadrovax^®) vaccine.

Methods

Children who completed their primary immunization were assessed for antibodies at 15–18 months of age, and then given a booster dose of DTwP–Hib vaccine. Reactogenicity and safety of the booster dose was evaluated.

Results

Both pentavalent vaccines demonstrated a good immune response at 15–18 months. Following the booster dose, all vaccinated subjects achieved protective titers against diphtheria, tetanus and Hib, whereas the response to pertussis antigen was ∼78%. Fever and irritability was noted in 24%, local pain in 51%, and swelling in 36% of the children following booster dose.

Conclusions

Primary immunization with either pentavalent vaccine induced an excellent immunity lasting till the second year of life. A booster dose with DTwP–Hib (Quadrovax^®) vaccine effectuated a good anamnestic response to all vaccine components, being specially strong for Hib in children previously vaccinated with SIIL liquid pentavalent vaccine (Pentavac^®). Also, the safety profile of SIIL quadrivalent vaccine (Quadrovax^®) administered as booster dose was acceptable.     

Seroprotection associated with infant vitamin A supplementation given with vaccines is not related to antibody affinity to Hepatitis B and Haemophilus influenzae type b vaccines

Vaccines are usually assessed by analyses of their safety and immunogenicity to determine the effectiveness of eliciting antibody responses against target organisms. However, it is equally important to establish antibody affinity because of its specific role in protection from infection. Antibody affinity can be determined by comparisons of various antibody concentrations in dose–response curves. During a study on the immunogenicity of a pentavalent vaccine in 888 infants, antibody affinity analyses of the hepatitis B and Haemophilus influenzae type b components were investigated in infants given 15 mg RE vitamin A with their vaccination and those who were not given vitamin A. In this paper we present the results of 222 infants; a 25% sub-sample of the original study. Analyses were carried out using dilutions of serum samples from fitted values corresponding to optical densities from antibody detection assays. These were obtained from the ligand binding equation and mid point titres in dose–response curves were then calculated. Vitamin A supplementation had no effect on the midpoint titres of Hepatitis B and H. influenzae type b vaccine derived antibodies. The significant effect of vitamin A supplementation on the Hepatitis B vaccine component observed in a previous seroprotection analysis is probably due to the amount of antibodies since affinity was unaffected.     

Safety of a quadrivalent meningococcal serogroups A,C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: Results of an open-label,randomized, phase 3b controlled study in healthy infants

Background

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants.

Methods

Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1–7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%).

Results

A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI −0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference −0.1% [95% CI −4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups.

Conclusion

In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone.     

Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs

In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age.     

Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study

Historically, Haemophilus influenzae (Hi) serotype b (Hib) caused most invasive Haemophilus infections worldwide, mainly in children. In 1989 routine childhood vaccination against Hib was initiated in Iceland. We conducted a population-based study of all patients in the country with Haemophilus spp. isolated from sterile sites (n = 202), from 1983 to 2008. Epidemiology, clinical characteristics of the infections and serotypes of the isolates were compared during the pre-vaccination (1983-1989) and post-vaccination era (1990-2008). Following the vaccination, the overall incidence of Hib decreased from 6.4 to 0.3/100,000 per year (p <0.05) whereas the incidence did not change significantly for infections caused by Haemophilus sensu lato not serotype b, hereafter referred to as non-type b Hi (0.9 vs 1.2, respectively). The most frequent diagnosis prior to 1990 was meningitis caused by Hib, which was subsequently replaced by pneumonia and bacteraemia caused by non-type b Hi. Most commonly, non-type b Hi were non-typeable (NTHi; 40/59), followed by Hi serotype f (14/59) and Hi serotype a (3/59). Pregnancy was associated with a markedly increased susceptibility to invasive Haemophilus infections (RR 25.7; 95% CI 8.0-95.9, p <0.0001) compared with non-pregnant women. The case fatality rate for Hib was 2.4% but 14% for non-type b Hi, highest at the extremes of age. Hib vaccination gives young children excellent protection and decreases incidence in the elderly due to herd effect in the community. Replacement with other species or serotypes has not been noted. Pregnant women are an overlooked risk group.     

宣传教育在提高Hib疫苗接种率中的作用探讨

目的:探讨宣传教育在提高Hib疫苗接种率中的作用。方法:对2008年1月1日～2009年10月31日期间来我院接受预防接种的所有Hib疫苗适龄儿童5164人,进行随机化分为普通接种组和宣传教育组,开展Hib疫苗接种工作,对两组儿童接种率进行比较,然后对普通组未接受接种儿童家长进行宣传教育,再次比较两组接种率。结果:普通组首次接种率明显低于宣传组P<0.01,经宣传教育后,普通组接种率明显上升,与宣传组无明显差异0.5>P>0.25。结论:接受预防接种Hib疫苗,可以降低我国的Hib疾病的发生,增进广大儿童的健康。     

An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children

Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥97.3% of ACWY-TT vaccinees had rSBA titres ≥1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.     

Bacterial meningitis and Haemophilus influenzae type b conjugate vaccine, Malawi

A retrospective database review showed that Haemophilus influenzae type b conjugate vaccine decreased the annual number of cases of H. influenzae type b meningitis in children in Blantyre, Malawi. Among young bacterial meningitis patients, HIV prevalence was high (36.7% during 1997-2009), and pneumococcus was the most common etiologic agent (57% in 2009).     

Pertussis vaccines: WHO position paper--recommendations

This article presents the WHO recommendations on the use of pertussis vaccines excerpted from the recently published Pertussis vaccines: WHO position paper. This document replaces the WHO position paper entitled Pertussis vaccines: WHO position paper published in the Weekly Epidemiological Record in January 2005. Footnotes to this paper provide a limited number of core references; their abstracts as well as a more comprehensive list of references may be found at http://www.who.int/immunization/documents/positionpapers/en/index.html. Grading tables which assess the quality of scientific evidence for key conclusions are also available through this link and are referenced in the position paper.In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This updated paper reflects the recent recommendations of WHO's Strategic Advisory Group of Experts on immunization, or SAGE.     

Immunoglobulin deficiency in children with Hib vaccine failure

Immunoglobulin deficiency has been reported in 21% of UK children with Hib vaccine failure but its clinical significance and long-term consequences are not known. This study aimed to estimate the prevalence of immunoglobulin deficiency in children with Hib vaccine failure several years after infection and to determine their risk of recurrent infections. The families of children who developed invasive Hib disease after prior immunisation were identified through national surveillance. A completed questionnaire and blood sample was provided by 170 children at a median of 4 years after infection, equivalent to 1035 child-years of follow-up. Nineteen (11.2%) children had immunoglobulin deficiency, including IgA (n = 12), IgM (n = 5) and all three immunoglobulin classes (n = 2). Immunoglobulin deficiency was associated with younger age (<2 years) at initial Hib disease (12/19 [63.2%] vs. 60/151 [39.7%], P = 0.05) and parental reporting of their child receiving >2 antibiotic courses annually in early childhood (11/19 [57.9%] vs. 39/151 [25.8%], P = 0.004].). In a logistic regression model, Hib vaccine failure cases that had received multiple antibiotic courses in early childhood were 3.8 times (95% CI, 1.4-10.6; P = 0.01) more likely to be immunoglobulin deficient at follow-up than those with fewer or no antibiotic courses. Thus, the prevalence of immunoglobulin deficiency in children with Hib vaccine failure at a median of four years after infection is half that reported at the time of the original infection. A proportion of children with Hib vaccine failure, especially where it occurs at a young age, appear to have a maturational delay in development of normal immunoglobulin concentrations.