Immunogenicity and safety of fully liquid DTaP₅-IPV-Hib compared with DTaP₃-IPV/Hib when both coadministered with a heptavalent pneumococcal conjugate vaccine (PCV7) at 2, 3, 4, and 12 to 18 months of age: a phase III, single-blind, randomised, controlled, multicentre study

This study compared immunogenicity and safety of DTaP₅-IPV-Hib to DTaP₃-IPV/Hib coadministered with PCV7 at 2, 3, and 4 months (primary series) and a fourth-dose booster at 12-18 months of age. Seroprotection rates for DTaP₅-IPV-Hib were high (noninferior to DTaP₃-IPV/Hib for the primary series) for antigens common to both vaccines and PCV7 antigens. Geometric mean concentration (GMC) for Hib antibodies were higher in the DTaP₅-IPV-Hib group than the DTaP₃-IPV/Hib group after the primary series and booster dose; GMCs or titers for other antigens were generally similar between groups after the primary series and booster dose. Safety profiles were similar between groups.     

吸附无细胞百白破、灭活脊髓灰质炎和b型流感嗜血杆菌（结合）联合疫苗（DTaP-IPV/Hib五联疫苗）应用技术指南

百日咳、白喉、破伤风、脊髓灰质炎（脊灰）、b型流感嗜血杆菌（Haemophilusinfluenzaetypeb,Hib）引起的感染性疾病是常见的严重危害人类健康,特别是儿童健康的传染病。预防接种是控制这5种疾病最经济、有效的措施,通常预防儿童这5种疾病要分别接种吸附百白破联合疫苗（DPT）、口服脊灰减毒活疫苗（OPV）和Hib疫苗,幼儿完成全程免疫累计需要接种11剂次。     

Risk of Haemophilus influenzae type b meningitis in Polish children varies directly with number of siblings: Possible implications for vaccination strategies

Background: In the absence of an effective vaccine, Haemophilus influenzae type b (Hib) meningitis has frequently been found to be the most common bacterial meningitis among children less than or equal to 5 years of age. This study was conducted prior to the introduction of Hib vaccine in Poland, and is the first case–control study of Hib meningitis in this country. Methods: A 1:3 matched case–control study was nested within a population-based surveillance study of Hib meningitis in children less than or equal to 5 years old in Poland. Controls were matched on the case's age at onset of disease and immunization center. Results: Having one or more siblings is a highly significant risk factor for Hib meningitis and, under the rare disease assumption, risk increases linearly with the increase in the number of siblings. The size of the living area of the home was not itself a significant risk factor for disease. Breast-feeding was not protective in contrast to previous studies. Childcare outside of the home was a significant risk factor for Hib meningitis especially among children greater than 16 months of age, whereas the effect of sibling number on Hib meningitis was much greater among the younger children. Conclusion: Risk of Hib meningitis approximately doubles for every unit increase in the number of siblings. Routine vaccination of Polish infants who have two or more siblings could potentially prevent half of the Hib meningitis cases.     

Lessons learned during the development and transfer of technology related to a new Hib conjugate vaccine to emerging vaccine manufacturers

The incidence of Haemophilus Influenzae type b (Hib) disease in developed countries has decreased since the introduction of Hib conjugate vaccines in their National Immunization Programs (NIP). In countries where Hib vaccination is not applied routinely, due to limited availability and high cost of the vaccines, invasive Hib disease is still a cause of mortality. Through the development of a production process for a Hib conjugate vaccine and related quality control tests and the transfer of this technology to emerging vaccine manufacturers in developing countries, a substantial contribution was made to the availability and affordability of Hib conjugate vaccines in these countries. Technology transfer is considered to be one of the fastest ways to get access to the technology needed for the production of vaccines. The first Hib conjugate vaccine based on the transferred technology was licensed in 2007, since then more Hib vaccines based on this technology were licensed.     

Immunogenicity and thermal stability of a combined vaccine against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases

The immunogenicity, structure and stability of a combined conjugate vaccine against Haemophilus influenzae type b and meningococcal serogroup C (Hib/MenC) were investigated. A rat model for immunogenicity showed that antibody responses to Hib and MenC in the combined vaccine were similar to or higher than those of individual conjugates given alone, or concomitantly at separate sites. At elevated temperatures, the combination vaccine was slightly more stable than a monovalent Hib-TT vaccine, with respect to molecular size, which could be attributed to differences in the formulations. Following 5 weeks incubation at 56 °C, there was some dissociation of high molecular weight conjugate without significant loss of saccharide integrity; however, this did not significantly affect the vaccine immunogenicity, demonstrating the stability of this lyophilized vaccine.     

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%–99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 µg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 µg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, {"type":"clinical-trial","attrs":{"text":"NCT01214889","term_id":"NCT01214889"}}NCT01214889).     

Immunogenicity and safety of the quadrivalent meningococcal vaccine MenACWY-TT co-administered with a combined diphtheria-tetanus-acellular pertussis vaccine versus their separate administration in adolescents and young adults: A phase III,randomized study

BackgroundThis study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults.MethodsIn this phase III, randomized, partially-blind study (NCT01767376), healthy 11–25-year-olds (N = 660) were randomized (1:1:1) to receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1 (Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum bactericidal assay using rabbit complement (rSBA). Anti-diphtheria (D), anti-tetanus (T), anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibody concentrations were assessed using enzyme-linked immunosorbent assays. Non-inferiority of immunogenicity was assessed using pre-defined clinical criteria. Safety was also evaluated.ResultsNon-inferiority of immunogenicity of MenACWY-TT and Tdap when co-administered versus their separate administration was demonstrated in terms of rSBA geometric mean titers (GMTs) for 4 meningococcal serogroups and of the percentage of participants with antibody concentrations >1 IU/ml for D and T. Among the pertussis antigens, non-inferiority criteria for geometric mean concentrations (GMCs) were reached for PT, but not met for FHA and PRN. Across all groups, ≥93.2% of participants had vaccine responses to each meningococcal serogroup, ≥99.1% were seroprotected against T and D, and ≥85.5% had booster responses to each pertussis antigen. Robust increases in antibody GMTs/GMCs were observed for all antigens between pre-and post-vaccination. Both vaccines had clinically acceptable safety profiles.ConclusionImmune responses to MenACWY-TT and to the T and D antigens from Tdap were not impacted by their co-administration. The lower antibody concentrations observed against the pertussis components may be of limited clinical relevance since robust anti-pertussis booster responses were observed. This study supports concurrent administration of the 2 vaccines in adolescents.     

Examination of universal purchase programs as a driver of vaccine uptake among US States, 1995–2014

BackgroundImmunization against numerous potentially life-threatening illnesses has been a great public health achievement. In the United States, the Vaccines for Children (VFC) program has provided vaccines to uninsured and underinsured children since the early 1990s, increasing vaccination rates. In recent years, some states have adopted Universal Purchase (UP) programs with the stated aim of further increasing vaccination rates. Under UP programs, states also purchase vaccines for privately-insured children at federally-contracted VFC prices and bill private health insurers for the vaccines through assessments.MethodsIn this study, we estimated the effect of UP adoption in a state on children’s vaccination rates using state-level and individual-level data from the 1995–2014 National Immunization Survey. For the state-level analysis, we performed ordinary least squares regression to estimate the state’s vaccination rate as a function of whether the state had UP in the given year, state demographic characteristics, other vaccination policies, state fixed effects, and a time trend. For the individual analysis, we performed logistic regression to estimate a child’s likelihood of being vaccinated as a function of whether the state had UP in the given year, the child’s demographic characteristics, state characteristics and vaccine policies, state fixed effects, and a time trend. We performed separate regressions for each of nine recommended vaccines, as well as composite measures on whether a child was up-to-date on all required vaccines.ResultsIn the both the state-level and individual-level analyses, we found UP had no significant (p < 0.10) effect on any of the vaccines or composite measures in our base case specifications. Results were similar in alternative specifications.ConclusionsWe hypothesize that UP was ineffective in increasing vaccination rates. Policymakers seeking to increase vaccination rates would do well to consider other policies such as addressing provider practice issues and vaccine hesitancy.