b型流感嗜血杆菌及其疫苗

 b型流感嗜血杆菌（Haemophilus influenzae type b,Hib）是导致婴幼儿严重细菌性感染的主要致病菌之一。Hib疫苗的研发和使用大大降低了Hib疾病的发病率。研究显示,Hib结合疫苗可有效预防婴幼儿侵袭性Hib疾病,且具有良好的安全性。此文就Hib的病原学、流行病学及疫苗研究进行综述。     

常规免疫接种b型流感杆菌结合疫苗的影响

作者利用丹麦全国疫苗接种登记和其他人口信息，在丹麦儿童中评价了b型流感杆菌(Hib)疫苗接种的免疫效果，主要目的是研究疫苗接种率和免疫接种程度的依从性、疫苗效果及群体免疫效果。丹麦于1993年5月将Hib疫苗纳入儿童免疫计划，免疫程序为5、6月龄初免、16月龄加强免疫，对所有6岁以下儿童给予补救免疫接种。1996年将加强免疫的年龄改为15月龄，1997年则将免疫程序改为3、5、12月龄。     

经DTP 10倍稀释的Hib结合疫苗的免疫原性和安全性

尽管全球每年有近 2 0 0万 b型流感杆菌( Hib)病患者 ,但目前全世界 Hib结合疫苗的接种覆盖率不到 8% ,高额的疫苗费用 (每剂 2 .5美元 )使得 Hib病负荷最高的发展中国家难以负担疫苗接种。作者通过一项随机试验比较了全剂量 ( 1 0 μg) Hib结合疫苗与经DTP1 0倍稀释的 Hib结合疫苗的免疫原性。　　将 1 6 8名健康儿童随机分为两组 ,一组儿童 ( 83名 )接种全剂量 Hib多糖 -破伤风类毒素结合疫苗 ( PRP- T) ,另一组儿童 ( 85名 )接种经 DTP1 0倍稀释的 Hib结合疫苗 (将1 0 μg全剂量 Hib结合疫苗重悬于 1 0人份DTP瓶中 )。婴儿分别…     

用于Hib结合疫苗生产的新型候选菌株的评价

目的 观察b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)760705株在连续传代过程中的稳定性.方法 将Hib 760705株工作种子批菌种连续传代,对第5、第8、第10代Hib培养物进行全面检测,包括培养特性(细菌培养、卫星试验)、染色镜检、生化反应,以检测第5、第8、第10代Hib的生物学特性.同时采用血清凝集试验和聚合酶链反应荚膜分型方法进行b型荚膜多糖稳定性检测.结果 Hib 760705株工作种子批培养物在连续传代过程中具有典型的细菌学特性,能够稳定地产生b型荚膜多糖.结论 Hib 760705株有明确的来源和背景,可以稳定传代,具备作为Hib结合疫苗生产用候选菌株的条件.     

常规免疫接种b型流感杆菌结合疫苗的影响

作者利用丹麦全国疫苗接种登记和其他人口信息 ,在丹麦儿童中评价了 b型流感杆菌 ( Hib)疫苗接种的免疫效果 ,主要目的是研究疫苗接种率和免疫接种程度的依从性、疫苗效果及群体免疫效果。丹麦于 1 993年 5月将 Hib疫苗纳入儿童免疫计划 ,免疫程序为 5、6月龄初免、1 6月龄加强免疫 ,对所有 6岁以下儿童给予补救免疫接种。 1 996年将加强免疫的年龄改为 1 5月龄 ,1 997年则将免疫程序改为 3、5、1 2月龄。　　作者对 758988名儿童进行疫苗接种与免疫接种程序依从性分析 ,结果显示 ,根据年龄、针次和免疫接种程序的不同 ,补救免疫接种程序的…     

b型流感杆菌结合疫苗接种后的免疫持久性

尽管目前建议在全球使用b型流感杆菌( Hib)结合疫苗,但尚不知其提供的免疫保护持久性。本文对8年前接种过Hib结合疫苗或Hib多糖( PS)疫苗的9～1 0岁的儿童进行研究,以评估Hib结合疫苗的免疫持久性及是否需要加强。　　作者将9～1 0岁的儿童分成3组:Hib结合疫苗组,37人,在3～1 8月龄接种过4针Hib结合疫苗;对照组,39人,以前未接种过任何Hib疫苗;Hib PS疫苗组,1 3人,在3～1 8月龄接种过4针Hib PS疫苗。3组儿童均注射1针Hib PS疫苗,免疫前及免疫后4周采血并分离血清,测定抗体浓度、亚类和亲和力。结果表明,Hib结合疫苗组儿童在2～1 0岁…     

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。     

婴儿初免DTPa-HBV-IPV/Hib六价联合疫苗的安全性、反应原性和免疫原性

由于推荐婴儿通过主动免疫来预防的儿童疾病种类逐渐增多,使得儿童6岁前的免疫程序日益复杂,免疫针次增多.为此,比较了初免六价联合疫苗--无细胞百日咳疫苗DTP(DTPa)-乙型肝炎疫苗(HBV)-脊髓灰质炎灭活疫苗(IPV)/b型流感杆菌(Hib)结合疫苗(DTPa-HBV-IPV/Hib)与分开接种DTPa-IPV/Hib和HBV在婴儿中的安全性、反应原性和免疫原性.     

Hib结合疫苗初免后9年加强免疫载体蛋白对抗Hib和TT抗体水平的影响

过去10年间，许多国家将b型流感杆菌（Hib）结合疫苗纳入婴儿免疫接种程序，但迄今为止，对婴儿期免疫过Hib疫苗的学龄儿童的血清抗Hib荚膜多糖（CPS）抗体浓度情况知之甚少。为此，瑞典哥德堡大学Claesson等在先前免疫过Hib-破伤风类毒素（TT）结合疫苗的儿童中分析了初免Hib—TT疫苗9年后的抗HibCPS抗体水平，并研究了此时加强1剂载体蛋白（如TT）能否提高抗Hib抗体水平。     

b型流感杆菌结合疫苗

b型流感杆菌(Hib)多糖-蛋白结合疫苗能有效控制侵袭性Hib病的流行.本文介绍了Hib结合疫苗的研制及应用情况,并对英国Hib结合疫苗免疫失败的原因进行了探讨.     

DTPa-HBV-IPV/Hib vaccine (Infanrix hexa)

Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B recombinant (adsorbed)-inactivated poliomyelitis-adsorbed conjugated Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib; Infanrix hexa)-inactivated poliomyelitis-absorbed conjugated Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) refers to Infanrix hexa trade mark.) provided high levels of seroprotection against diphtheria toxoid, tetanus toxoid, poliovirus 1, 2 and 3, pertussis antigens (pertussis toxoid, filamentous haemagglutinin and pertactin), hepatitis B virus surface antigen and H. influenzae polyribosyl-ribitol-phosphate (PRP) antigen. Most infants (97%) had anti-PRP levels >/=0.15 micro g/mL after a booster dose at 18 months. Primary vaccination with the DTPa-HBV-IPV/Hib vaccine produced a similar immune response to that with two different pentavalent plus monovalent vaccine combinations. Coadministration of DTPa-HBV-IPV/Hib vaccine and a heptavalent pneumonococcal conjugate vaccine resulted in a high level of seroprotection and was well tolerated. Primary or booster vaccination with DTPa- HBV-IPV/Hib vaccine was well tolerated. Commonly reported local adverse reactions included redness, pain and swelling. Systemic symptoms were usually mild to moderate, and included fussiness, fever, restlessness and sleepiness.     

A new DTPw-HBV/Hib vaccine: immune memory after primary vaccination and booster dosing in the second year of life

The response to booster vaccination at 15-18 months of age and the presence of immune memory in 10-month old children, primed with a new combined diphtheria-tetanus-hepatitis B-whole cell pertussis vaccine extemporaneously mixed with Haemophilus influenzae type b-tetanus toxoid conjugate (DTPw-HBV/Hib) from new antigen sources and containing 2.5 microg polyribosyl-ribitol-phosphate (PRP) was assessed. Primary vaccination with the new DTPw-HBV/Hib vaccine was immunogenic and of comparable tolerability to commercially available Tritanrix HepB/Hiberix. Children were boosted with DTPw-HBV, DTPw-HBV/Hib or separate DTPw-HBV+Hiberix. Immune memory was assessed through administration of 10 microg PRP polysaccharide. Anti-PRP antibody GMCs increased substantially after the challenge in DTPw-HBV/Hib-primed subjects indicating the presence of immune memory. One month after the booster dose, 100% of subjects had seroprotective antibody concentrations against PRP, diphtheria and tetanus, >95% were seroprotected against hepatitis B, > or =94.0% had a pertussis booster response. Substantial increases in antibody GMCs against all antigens were observed. Swelling >20 mm was the most common Grade 3 solicited symptom reported (up to 26.0% of subjects). Fever >39.5 degrees C was uncommon (>2.5%). Eleven large swelling reactions were reported; none involved an adjacent joint. One serious adverse event occurred that was considered unrelated to vaccination. This new DTPw-HBV/Hib vaccine with new vaccine components and 2.5 microg PRP induced effective priming against Hib evidenced by a vigorous anamnestic response on exposure to PRP polysaccharide. The booster dose was immunogenic and the safety profile was acceptable. Combined DTPw-HBV and DTPw-HBV/Hib vaccines using new vaccine antigen sources will promote continued supply of combined DTPw-based vaccines to global mass vaccination campaigns.     

Haemophilus influenzae type b (Hib) vaccine: an effective control strategy in India

Haemophilus influenzae type b (Hib) is an encapsulated, non-motile and non-spore-forming Gram-negative coccobacillus which causes severe pneumonia, meningitis and other life threatening illnesses. Hib disease affects almost exclusively (95%) children aged less than 5 years throughout the world. The mean age of onset is 6-24 months after which it declines gradually until age 5 years. The World Health Organization (WHO) estimates that Hib is responsible for 3 million cases of serious illnesses and approximately 386,000 deaths worldwide each year in children aged under 5 years. In the latest position paper on Hib vaccine, WHO recommended the inclusion of Hib conjugate vaccines in all routine infant immunization programs without waiting for local disease-burden data. The WHO and the Global Alliance for Vaccine Immunization (GAVI) have been working to expand supplies of Hib vaccine, reduce vaccine cost, and assist especially low-income countries with vaccine introduction. Hib vaccine is safe, highly effective and readily available in the market. Hib vaccine has been shown to be > 95% efficacious in diverse populations around the world. Globally, hundreds of millions of doses of Hib vaccine have been administered in the last 2 decades. More than 160 countries are using Hib vaccine in national immunization programmes and around 25 countries planning to introduce. Hib vaccination fits into the India's national immunization schedule.     

冻干b型流感嗜血杆菌结合疫苗强制降解的稳定性研究

目的  通过强制降解试验观察冻干b型流感嗜血杆菌（Haemophilus influenzae type b，Hib）结合疫苗在高温、高湿、强光照射下的稳定性，为疫苗生产工艺、包装材料和贮存条件的确定提供科学依据。 方法  分别采用40 ℃温度、（75±5）%相对湿度、（4 500 ±500）lx光照处理冻干Hib结合疫苗，取样进行疫苗的全部项目检测。 结果  疫苗经40 ℃处理10 d，水分由2.0%上升至2.9%，多糖分子大小（分配系数小于0.2的洗脱液回收率）由94%下降至85%，但仍分别符合≤3.0%和＞60%的质量标准；而高分子结合物含量由87%降至75%，不符合≥80%的质量标准。（75±5）%相对湿度和（4 500±500）lx光照处理10 d对疫苗的影响不明显，疫苗质量指标仍符合规定。结论  高温是影响冻干Hib结合疫苗稳定性的主要因素。     

Immunologic response to Hib tetanus toxoid conjugated vaccine coadministered with DTPa either mixed or in two separate injections in toddlers not primed with Hib vaccine

This open randomized study compared the immunogenicity and safety of a diphtheria-tetanus-acellular pertussis (DTPa) and H. influenzae polyribosylribitol phosphate conjugated to the tetanus toxoid (Hib-PRP-T) vaccine (mixed prior to administration) with separate injections of DTPa and Hib vaccines in toddlers aged two years. A total of 119 children (60 mixed; 59 separate administration), primed with DTPw, but not with Hib vaccine were enrolled. Prior to immunization only 10.3% of toddlers had anti-PRP antibody titres > or =1.0 microg/ml, compared with all children on Days 7 and 30. The anti-PRP and anti-tetanus antibody geometric mean concentrations were lower after the combined DTPa/Hib vaccine compared to separately administered vaccines (47.16 microg/ml vs 78.36 microg/ml and 24.95 IU/ml vs 40.63 IU/ml, respectively). One month after vaccination all children had anti-tetanus and anti-diphtheria antibody titres above the protective level of > or =0.1 IU/ml. The rates of recorded adverse events were similar and mostly mild or moderate in intensity whether the vaccines were combined as a single injection or given separately. We conclude that in 2-year old children, previously not immunized against Hib, a single dose of DTPa and Hib was safe and highly immunogenic irrespective of whether it was given as a combined vaccine or separate injections. Although the increase in anti-T and early (7-10 days after) anti-PRP concentrations was greater when the vaccine components were given separately than after combined administration, the DTPa/Hib combined vaccine would provide an effective method of delivering primary Hib vaccination in unprimed toddlers.     

Preventing Haemophilus influenzae type b disease

The pathogenesis of Haemophilus influenzae type b (Hib) disease and methods for limiting spread of outbreaks of Hib disease are reviewed. Many strains of H. influenzae are surrounded by an outer polysaccharide capsule; of the six antigenically distinct capsular types, Hib is the predominant cause of such serious infections as meningitis, especially among children younger than five years of age. The age-specific incidence of Hib disease appears to be related to the relatively small concentrations of anti-Hib antibody present in young children. Children younger than 48 months of age who reside in the same house or attend the same day-care center as a child who develops Hib disease appear to be at increased risk for contracting systemic Hib infections. Prophylactic administration of rifampin 20 mg/kg once daily for four days can substantially decrease asymptomatic carriage of Hib in household contacts of the index patient and reduce the incidence of secondary Hib disease. The index patient should also receive prophylactic rifampin therapy before discharge from the hospital; i.v. antibiotics may cure the systemic infection but allow nasopharyngeal colonization to persist. A vaccine formulated from purified Hib capsular polysaccharide confers protection to more than 90% of children vaccinated at a minimum age of 24 months. Other candidates for vaccination include children between the ages of two and five years who attend day-care centers and children with anatomic or functional asplenia or malignancies. The vaccine is not effective in children younger than 18 months of age (who account for 60% of Hib disease in the U.S.); methods to increase vaccine immunogenicity in young infants are being evaluated. Reduction of Hib disease in the U.S. may be possible through widespread use of the new vaccine.     

Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults

The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.     

DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa™): A Guide to Its Use in Infants

Infanrix hexa?, a diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis, and Haemophilus influenzae type b (Hib) conjugate vaccine, is indicated for primary and booster vaccination of infants. Available clinical data from more than a decade of experience with the vaccine indicate that primary and booster vaccination with Infanrix hexa? is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B, and disease caused by Hib.     

用于Hib结合疫苗生产的新型候选菌株的评价

目的 观察b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)760705株在连续传代过程中的稳定性.方法 将Hib 760705株工作种子批菌种连续传代,对第5、第8、第10代Hib培养物进行全面检测,包括培养特性(细菌培养、卫星试验)、染色镜检、生化反应,以检测第5、第8、第10代...