Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B vaccine during the primary immunization course?

A combined hepatitis A/B vaccine (Twinrix Adult) has been licensed in Germany since 1997. We investigated possible differences in immunogenicity and safety when changing over from vaccinations with monovalent vaccines made by different manufacturers to vaccinations with the combined hepatitis A/B vaccine in an open, randomized, multicenter trial. We therefore compared four different schemes changing over from concomitant vaccinations with monovalent vaccines against hepatitis A and B (Havrix 1440+Engerix-B or Vaqta+Gen H-B-Vax) to combined vaccination against hepatitis A+B with three injections of the combined hepatitis A/B vaccine (0, 1, and 6 month schedule). Local and general symptoms were mostly mild in all five groups. With complete three-dose course using the combined vaccine or an early changeover from monovalent vaccines to the combined vaccine, higher overall anti-HBs seroprotection rates and geometric mean concentrations (GMCs) against hepatitis B could be achieved as early as after 2 months as compared to those groups switching later to the combined vaccine. This study demonstrated for the first time that switching from monovalent hepatitis A and B vaccinations to the combined hepatitis A and B vaccination has no negative influence on the tolerability and improves the immunogenicity.     

New acellular pertussis-containing paediatric combined vaccines

Combined pediatric vaccines have the advantages of conferring protection against multiple common infectious diseases with a reduced number of injections. Their use should lead to better compliance to recommended vaccination schedules. Diphtheria (D), tetanus (T) and whole-cell pertussis vaccine (P) have been successfully combined, with or without inactivated poliovirus vaccine (IPV) in the same syringe for many years. Recently developed acellular pertussis (aP) Haemophilus influenzae type B (Hib), inactivated poliomyelitis virus and hepatitis B vaccines are ideal candidates for inclusion in current combined vaccines. Nevertheless, the development of new combinations has to face preclinical and clinical issues: the appropriate formulation of the new antigen(s) and other vaccine components needs to be determined to ensure compatibility and guard against potential additive or unexpected adverse reactions; potential immunological interference between antigens and the negative impact of other vaccine components on immunogenicity may occur, and these have to be examined also. Whole-cell pertussis vaccines are highly protective against whooping cough, but the severe adverse reactions that these vaccines sometimes produce have led to hesitation over their use, including the decision of some countries to stop pertussis immunization. To increase the acceptability of pertussis vaccination, Pasteur Mérieux Connaught has developed a combined D, T and a two-component acellular pertussis vaccine (DTaP), composed of purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA), which has been shown to be effective in an efficacy trial conducted in Senegal. Acellular DTaP vaccines are immunogenic and have a better safety profile than DTP vaccines, when given either for the primary series, for the booster vaccination or for both. In order to meet worldwide demands, the combined DTaP-IPV or DTP-IPV has been developed for countries where IPV is recommended. Following the encouragement of the WHO, an H. influenzae type B tetanus-conjugated (Act-HIB) vaccine, has been combined in a full liquid formulation with the whole-cell DTP. This vaccine showed a good safety and immunogenicity profile in infants and in toddlers. A combined DTaP-IPV-PRP-T vaccine (where the Act-HIB vaccine is reconstituted by the full-liquid DTaP-IPV) also has been successfully developed both for the primary series and for booster vaccination; although, a reduced immunogenicity against PRP observed after the primary series, this did not affect vaccine priming. Hepatitis B immunization campaigns targeting high-risk groups have failed to control the disease in areas of low endemicity. In 1992, the WHO recommended that hepatitis B vaccination should be integrated into the EPI in all countries by 1997-1999. For that purpose, hepatitis B vaccine is currently evaluated in pediatric combined vaccines. Developing new combination vaccines is a difficult but essential process for maintaining high immunization rates worldwide against infectious diseases, provided that the costs are acceptable. New combined vaccines including pneumococcal and meningococcal component are under wide-scale development.     

Post-licensure monitoring of HPV vaccine in the United States

Post-licensure evaluation of vaccines plays an important role in monitoring the progress of immunization programs, demonstrating population impact of vaccines, and providing data for ongoing policy decisions. Two human papillomovirus (HPV) vaccines are licensed and recommended for use in females in the United States, a quadrivalent human HPV vaccine, licensed in 2006 and a bivalent vaccine HPV vaccine licensed in 2009. HPV vaccination is recommended for females 11 or 12 years of age with catch-up vaccination through age 26 years. Post-licensure monitoring of the HPV vaccine program has included some of the same systems established for other vaccines, such as those for vaccine safety and coverage monitoring. However, monitoring HPV vaccine impact on infection and disease outcomes has required new efforts. While there are well established cancer registries in the United States, it will take decades before the impact of vaccine on cervical cancer is observed. More proximal measures of vaccine impact include outcomes such as prevalence of HPV vaccine types, incidence of cervical precancers and genital warts. We review systems in place or being established for post-licensure monitoring of HPV vaccine in the United States.     

Safety and immunogenicity of fully liquid DTaP₅-IPV-Hib pediatric combination vaccine (Pediacel®) compared to DTaP₃-HBV-IPV/Hib (Infanrix® Hexa) when coadministered with heptavalent pneumococcal conjugate vaccine (PCV7) as a booster at 11-18 months of age: a phase III, modified double-blind, randomized, controlled, multicenter study

This study compared the safety and immunogenicity of DTaP?-IPV-Hib vaccine (followed by monovalent hepatitis B vaccine [HBV]) and DTaP?-HBV-IPV/Hib vaccines, both coadministered with PCV7, as a fourth-dose booster in toddlers 11-18 months who had a hexavalent vaccine primary series. The fever rate within 4 days of DTaP?-IPV-Hib was noninferior to DTaP?-HBV-IPV/Hib. DTaP?-IPV-Hib induced a marked immune response and had a similar safety and immunogenicity profile compared with DTaP?-HBV-IPV/Hib. Fully liquid DTaP?-IPV-Hib can be used as a booster after a hexavalent vaccine primary series; where required, a fourth dose of monovalent HBV can be administered after DTaP?-IPV-Hib (NCT ID: NCT00355654).     

Vaccinomics: A scoping review

BackgroundThis scoping review summarizes a key aspect of vaccinomics by collating known associations between heterogeneity in human genetics and vaccine immunogenicity and safety.MethodsWe searched PubMed for articles in English using terms covering vaccines routinely recommended to the general US population, their effects, and genetics/genomics. Included studies were controlled and demonstrated statistically significant associations with vaccine immunogenicity or safety. Studies of Pandemrix®, an influenza vaccine previously used in Europe, were also included, due to its widely publicized genetically mediated association with narcolepsy.FindingsOf the 2,300 articles manually screened, 214 were included for data extraction. Six included articles examined genetic influences on vaccine safety; the rest examined vaccine immunogenicity. Hepatitis B vaccine immunogenicity was reported in 92 articles and associated with 277 genetic determinants across 117 genes. Thirty-three articles identified 291 genetic determinants across 118 genes associated with measles vaccine immunogenicity, 22 articles identified 311 genetic determinants across 110 genes associated with rubella vaccine immunogenicity, and 25 articles identified 48 genetic determinants across 34 genes associated with influenza vaccine immunogenicity. Other vaccines had fewer than 10 studies each identifying genetic determinants of their immunogenicity. Genetic associations were reported with 4 adverse events following influenza vaccination (narcolepsy, GBS, GCA/PMR, high temperature) and 2 adverse events following measles vaccination (fever, febrile seizure).ConclusionThis scoping review identified numerous genetic associations with vaccine immunogenicity and several genetic associations with vaccine safety. Most associations were only reported in one study. This illustrates both the potential of and need for investment in vaccinomics. Current research in this field is focused on systems and genetic-based studies designed to identify risk signatures for serious vaccine reactions or diminished vaccine immunogenicity. Such research could bolster our ability to develop safer and more effective vaccines.     

Considerations for human papillomavirus (HPV) vaccination of mid-adult women in the United States

In the United States, human papillomavirus (HPV) vaccination is recommended for 11 or 12 year old girls, with catch-up vaccination through age 26 years. Data are available for women over the age of 26 years on immunogenicity for both quadrivalent and bivalent HPV vaccines and on efficacy for the quadrivalent HPV vaccine. If HPV vaccines are licensed for use in women over 26 years of age (mid-adult women), recommendations for this age group will need to be considered. This review summarizes vaccine efficacy and immunogenicity data in mid-adult women, and addresses epidemiologic data related to key questions for consideration of vaccine recommendations for women over age 26 years.     

Recombinant versus plasma-derived hepatitis B vaccines: issues of safety, immunogenicity and cost-effectiveness

Any attempt to reduce the incidence of hepatitis B on a worldwide scale requires the availability of large quantities of potent, safe and affordable hepatitis B vaccine. However, ongoing doubts or concerns--justified or not--persist about the comparative safety, immunogenicity and cost-effectiveness of commercially available hepatitis B vaccines, whether derived from plasma or produced via recombinant expression systems. This review compares plasma versus recombinant hepatitis B vaccines in terms of these alleged differences and in the light of increasing clinical data acquired following administration of recombinant yeast-derived hepatitis B vaccines.     

Immunogenicity and reactogenicity of the combined hepatitis A and B vaccine in young adults

The combination of hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccinations can offer convenience, increased compliance and cost saving. We have studied the immunogenicity, reactogenicity and safety of combined hepatitis A and B vaccination in young adults (16-35 years old). Eighty healthy young adults were divided into two random groups. One group received the combined hepatitis A and B vaccine (HAB) in one arm while the other group was administered concomitant hepatitis A and B vaccines (HAV + HBV) in the right and left arms, respectively. The immunogenicity, reactogenicity and safety were assessed after each dose in both the groups. In local symptoms, the percentage of the combined HAB group was lower than the HAV + HBV group, and the general symptoms were noted in approximately 30% of each group without any significant difference. No serious adverse effects were noted. All the subjects were seropositive for antibody to hepatitis A virus (anti-HAV) after one dose of vaccine, and remained seropositive after three doses in both groups. The seropositive rate for antibody to hepatitis B surface antigen (anti-HBs) was significantly higher (84%) in the combined HAB group than the concomitant HAV + HBV group (62%), (p<0.05) after dose two, and all the subjects were seropositive (100%) after the third dose. The GMTs of anti-HAV and anti-HBs were not significantly different between groups 1 and 2 (p>0.1) except in month 6 when the GMT of anti-HBs was higher in HAB group (p=0.0039). The combined HAB vaccine was found to be safe, well tolerated and had less local symptoms in young adults. The immunogenicity and reactogenicity were similar to the concomitant HAV + HBV vaccines.     

Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

Purpose

This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone.

Methods

Healthy girls (9-15 years) were age-stratified (9, 10-12, and 13-15 years) and randomized to receive HPV (n = 270), HAB (n = 271), or HPV + HAB (n = 272). Vaccines were administered at months 0, 1, and 6. Immunogenicity was evaluated at months 0 and 7.

Results

The hepatitis A immune response was noninferior for HPV + HAB, versus HAB, for seroconversion rates (100% in each group) and geometric mean antibody titers (GMTs) (95% CI) (4,504.2 [3,993.0-5,080.8] and 5,288.4 [4,713.3-5,933.7] mIU/mL, respectively). The hepatitis B immune response was noninferior for HPV + HAB, versus HAB, for anti-HBs seroprotection rates (98.3% and 100%); GMTs were 3,136.5 [2,436.0-4,038.4] and 5,646.5 [4,481.3-7,114.6] mIU/mL, respectively. The HPV-16/18 immune response was noninferior for HPV + HAB, versus HPV, for seroconversion rates (99.6% and 100% for both antigens) and GMTs (22,993.5 [20,093.4-26,312.0] and 26,981.9 [23,909.5-30,449.1] EL.U/mL for HPV-16; 8,671.2 [7,651.7-9,826.6] and 11,182.7 [9,924.8-12,600.1] EL.U/mL for HPV-18, respectively). No subject withdrew because of adverse events. No vaccine-related serious adverse events were reported. Immune responses and reactogenicity were similar in girls aged 9 years compared with the entire study population.

Conclusions

Results support coadministration of HPV-16/18 vaccine with HAB vaccine in girls aged 9-15 years. The HPV-16/18 vaccine was immunogenic and generally well tolerated in 9-year-old girls.     

Immunogenicity and safety of human papillomavirus vaccine coadministered with other vaccines in individuals aged 9–25 years: A systematic review and meta-analysis

IntroductionAdolescents and young adults are at a high risk of developing human papillomavirus (HPV) infections, which can be prevented with the use of vaccines. Moreover, a combined immunization strategy for administration of HPV vaccines with other routine vaccines may lead to better compliance. We aim to comprehensively evaluate immunogenicity and safety in the case of concomitantly administered HPV vaccine in individuals aged 9–25 years.MethodsRelevant studies, published up to December 27, 2018, were identified through searches of Medline/PubMed, EMBASE, Web of Knowledge. The pooled relative risk (RR) of immunogenicity and safety information pertaining to the concomitant administration of HPV vaccines with other routine vaccines in healthy participants aged 9–25 years were evaluated.ResultsA total of 13 papers (11,657 participants) were included in this meta-analysis. The analyses showed that, between the concomitant and nonconcomitant administration groups, the seroconversion rate for the specific antibodies against all HPV types (type 16-, 18-, 6-, 11-, 31-, 33-, 45-, 52-, and 58) were the same (the pooled RR = 1.00, 95% confidence interval (CI) of 1.00–1.00); for the bivalent HPV (2vHPV) vaccine, the risks of local adverse events showed no significant difference (the pooled RR = 1.00, 95%CI: 0.97–1.04), and the risks of systemic adverse events were almost similar (the pooled RR = 1.10, 95% CI: 1.03–1.18); for the non-bivalent HPV (4vHPV and 9vHPV) vaccines, the risks of local adverse events were slightly higher in the concomitant administration groups (the pooled RR = 1.31, 95%CI: 1.17–1.47), and the risks of systemic adverse events were higher in the concomitant administration groups (the pooled RR = 2.09, 95% CI: 1.69–2.59).ConclusionsWe believe that the concomitant administration of other vaccines along with HPV vaccine is acceptable and there is no interference with the immune response to HPV vaccine. Concomitant vaccine administration has the potential to minimize the number of vaccination visits, leading to increased compliance, hence more effective disease prevention.     

Safety and immunogenicity of co-administered quadrivalent human papillomavirus (HPV)-6/11/16/18 L1 virus-like particle (VLP) and hepatitis B (HBV) vaccines

Adolescents and young adults are at high risk for human papillomavirus (HPV) and hepatitis B virus (HBV) infections, which are preventable by currently available, safe and effective, prophylactic vaccines. However, development of a combined immunization strategy may lead to better compliance for these vaccines, thereby contributing to the overall goal of protection against these diseases. This study assessed the safety and immunogenicity of co-administered quadrivalent HPV-6/11/16/18 L1 VLP and HBV vaccines in women (n=1877) aged 16-23 years. Co-administration of HPV and HBV vaccines induced robust anti-HPV-6, HPV-11, HPV-16, HPV-18 geometric mean titers (GMTs) and > or =99% seroconversion rates (Month 7) that were both non-inferior (p<0.001) to those induced by HPV vaccine alone. High Month 7 anti-HBs GMTs were also observed following concomitant vaccination. These GMTs were lower compared to those induced by the HBV vaccine itself; however, >96% of subjects achieved an anti-HBs seroprotection level of > or =10 mIU/mL that was non-inferior (p<0.001) to that of HBV vaccine alone. Overall, co-administered and individual vaccines were generally well-tolerated and did not interfere with the immune response of either vaccine (ClinicalTrials.gov number, NCT00092521).     

Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1-11-year-old children

This study was conducted to compare the reactogenicity, immunogenicity and safety of a combined two-dose (0, 6 months) hepatitis A and B vaccine (720ELU HAV, 20 mcg HBsAg) with the established three-dose (0, 1 and 6 months) hepatitis A and B vaccine (360ELU HAV, 10 mcg HBsAg). A total of 511 children aged 1-11 years who had not previously received a hepatitis A or B vaccine were enrolled in the study. Both vaccines were well tolerated, and were shown to be safe and immunogenic. The analysis, stratified according to two age groups (1-5 year and 6-11-year-old children) demonstrated that the reactogenicity profile of the two-dose schedule was at least as good as that of the established schedule. Both vaccines and schedules provided at least 98% seroprotection against hepatitis B and 100% seroconversion against hepatitis A, 1 month after the end of the vaccination course (Month 7).     

Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles-mumps-rubella or a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12-18 months

Two studies were undertaken to investigate the concomitant administration of combined hepatitis A/B vaccine with a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with Haemophilus influenzae vaccine (DTPa-IPV/Hib), or with a measles-mumps-rubella vaccine (MMR), during the second year of life. On completion of the vaccination course, all subjects were seropositive or seroprotected against all antigens except for one subject who was seronegative for anti-PT. Seropositivity and seroprotection rates for all other antibodies were comparable to reference values for each vaccine component, indicating that the immunogenicity of MMR, DTPa-IPV/Hib and combined hepatitis A/B vaccines is not impaired by co-administration. All vaccines were well tolerated.     

Comparison of the implementation of human papillomavirus and hepatitis B vaccination programs in the United States: Implications for future vaccines

Vaccines for two viruses which cause cancer, human papillomavirus (HPV) and hepatitis B virus (HBV), are recommended for all children in the United States. Numerous parallels exist between the two vaccines in addition to their roles in cancer prevention, including transmission through sexual contact, multiple doses needed for series completion, and vaccine administration in adolescence for HPV and in the initial phase of the HBV vaccination program. All of these factors were viewed as potential barriers to achieving high rates of coverage, yet the ultimate success of the HBV vaccination program led to predictions that similarly high rates of coverage could be achieved for the HPV vaccine. However, currently, only the recommendation for HBV vaccination is supported by mandates for school entry in most states. Uptake of the HPV vaccine has lagged far behind U.S. goals for public health promotion. The aim of this paper is to examine factors which may account for the divergent pathways of the two vaccines. Four main factors are identified: logistical challenges of vaccine administration, attitudes of parents and healthcare providers, safety concerns, and cost. For each factor examined, recommendations are offered to confront similar barriers likely to arise for future vaccines. The authors conclude that gender-neutral state mandates coupled with school-located vaccination programs, stronger gender-neutral messaging from pharmaceutical companies and healthcare providers, and younger age of vaccine administration, if approved, present the most promising approaches to improving uptake of the HPV vaccine, and similar vaccines down the road.     

Immunogenicity of a combined hepatitis A and B vaccine in healthy young adults

Combining several vaccines in a single formulation can change the potency of the vaccine antigens. Previous studies suggested a higher immunogenicity of a new combined hepatitis A and B vaccine compared with the monovalent hepatitis B vaccine. We investigated the immune response to hepatitis B surface antigen 1 month after the third vaccine dose in 282 healthy adults who had received either a monovalent hepatitis B vaccine (n=148) or the combined hepatitis A/B vaccine (n=134). A slight trend towards higher geometric mean titres of anti HBs was found at this point in time in the group immunised with the combined vaccine, especially in the few vaccinees with preexisting antibodies against hepatitis A virus. However none of these differences was statistically significant, arguing against an advantage of the combined vaccine regarding hepatitis B immunisation.     

A tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when co-administered with Twinrix(®) in subjects aged 11-17 years: an open, randomised, controlled trial

The co-administration of the tetravalent meningococcal conjugate vaccine, MenACWY-TT, with a licensed hepatitis A and B vaccine, HepA/B (Twinrix^®), was compared to their separate administration in this open, randomised, controlled study. Healthy subjects 11-17 years of age (n = 611) were randomised (3:1:1) to receive both vaccines, MenACWY-TT alone or HepA/B alone. The co-administration of both vaccines was shown to be non-inferior to their individual administration. At seven months after the first vaccination, 99.4-100% of the subjects who received both vaccines co-administered showed seroprotection against all meningococcal serogroups and at least 99.1% of them were seropositive for hepatitis A and seroprotected against hepatitis B. This study suggests that MenACWY-TT vaccine could be co-administered with HepA/B without adversely impacting the immunogenicity, safety and reactogenicity of either of the vaccines.     

Country recommendations on the inclusion of HPV vaccines in national immunization programmes among high-income countries, June 2006-January 2008

We analysed country recommendations and funding plans finalized through January 2008 for the inclusion of quadrivalent and bivalent human papillomavirus (HPV) vaccines in national immunization programmes. Fifteen industrialized countries have recommended HPV vaccine use based on careful review of scientific evidence and cost-effectiveness. There was a strong consensus among the guidelines regarding assessment of vaccine safety and efficacy, selection of primary target populations for vaccination, vaccine delivery strategies, and the need for vaccinated females to seek cervical cancer screening. The analysis informs ongoing discussions in several countries considering HPV vaccines for national immunization programmes and discussions at the World Health Organization about global recommendations for HPV vaccine use for national immunization programmes.     

Awareness among adults of vaccine-preventable diseases and recommended vaccinations,United States, 2015

BackgroundAdults are recommended to receive select vaccinations based on their age, underlying medical conditions, lifestyle, and other considerations. Factors associated with awareness of vaccine-preventable diseases and recommended vaccines among adults in the United States have not been explored.MethodsData from a 2015 internet panel survey of a nationally representative sample of U.S. adults aged ≥19 years were analyzed to assess awareness of selected vaccine-preventable diseases and recommended vaccines for adults. A multivariable logistic regression model with a predictive marginal approach was used to identify factors independently associated with awareness of selected vaccine-preventable infections/diseases and corresponding vaccines.ResultsAmong the surveyed population, from 24.6 to 72.1% reported vaccination for recommended vaccines. Awareness of vaccine-preventable diseases among adults aged ≥19 years ranged from 63.4% to 94.0% (63.4% reported awareness of HPV, 71.5% reported awareness of tetanus, 72.0% reported awareness of pertussis, 75.4% reported awareness of HZ, 75.8% reported awareness of hepatitis B, 83.1% reported awareness of pneumonia, and 94.0% reported awareness of influenza). Awareness of the corresponding vaccines among adults aged ≥19 years ranged from 59.3% to 94.1% (59.3% HZ vaccine, 59.6% HPV vaccine, 64.3% hepatitis B vaccine, 66.2% pneumococcal vaccine, 86.3% tetanus vaccines, and 94.1% influenza vaccine). In multivariable analysis, being female and being a college graduate were significantly associated with a higher level of awareness for majority of vaccine-preventable diseases, and being female, being a college graduate, and working as a health care provider were significantly associated with a higher level of awareness for majority of corresponding vaccines.ConclusionsAlthough adults in this survey reported high levels of awareness for most vaccines recommended for adults, self-reported vaccination coverage was not optimal. Combining interventions known to increase uptake of recommended vaccines, such as patient reminder/recall systems and other healthcare system-based interventions, and ensuring patients’ vaccination needs are assessed, are needed to improve vaccination of adults.     

龙口市健康儿童甲乙型肝炎联合疫苗加强免疫效果评价

[目的]评价甲乙型肝炎联合疫苗一针加强免疫程序的免疫效果和安全性,为完善甲肝疫苗和乙肝疫苗免疫预防策略提供决策依据。[方法]选择210名24～38月龄儿童,随机分为2组：实验组接种1剂次甲乙肝联合疫苗,对照组接种1剂次甲肝灭活疫苗。免后1个月,采用定量微粒子酶联免疫法检测甲肝抗体,采用抗-HBs化学发光法检测乙肝抗体,评价免疫前后甲、乙肝抗体水平（GMC）和阳性率。并对受试者进行连续3d体温及可能发生的任何临床症状观察和随访,以评价其安全性。[结果]对照组（甲肝疫苗组）加强免疫1个月后甲肝抗体阳性率由免前的95．20％上升到100．00％,GMC增长倍数达55．74倍。实验组（甲乙联苗组）甲肝抗体阳性率由免前的88．80％上升到98．90％,GMC增长58．35倍。乙肝抗体阳性率由免前的的72．90％上升到97．80％,增长24．90％;GMC由免前的22．20mIU／ml上升到1226．10mIU／ml,增长54．50倍。观察到12例不良反应,均为发热,发生率为5．74％,未发现其他不良反应。[结论]甲乙型肝炎联合疫苗进行加强免疫具有良好的免疫原性和安全性,建议增加1剂次甲乙联苗加强免疫程序,帮助接种者获得长期的甲肝、乙肝抗体保护。     

Aluminum in vaccines: Does it create a safety problem?

For almost a century, aluminum (Al) in the form of Al oxyhydroxide (a crystalline compound), Al hydroxyphosphate (an amorphous Al phosphate hydroxide), Al phosphate, and Al potassium sulfate has been used to improve the immunogenicity of vaccines. Al is currently included in vaccines against tetanus, hepatitis A, hepatitis B, human papillomavirus, Haemophilus influenzae type b, and infections due to Streptococcus pneumoniae and Neisseria meningitidis. Official health authorities consider the inclusion of Al in most of the presently recommended vaccines to be extremely effective and sufficiently safe. However, the inclusion of Al salts in vaccines has been debated for several years because of studies that seem to indicate that chronic Al exposure through vaccine administration can interfere with cellular and metabolic processes leading to severe neurologic diseases. Children, who in their first years of life receive several vaccine doses over a reduced period of time, would be most susceptible to any risk that might be associated with vaccines or vaccine components. The main aim of this paper was to discuss the data presently available regarding Al neurotoxicity and the risk for children receiving vaccines or other pharmaceutical preparations containing Al. Analysis of the literature showed that no apparent reason exists to support the elimination of Al from vaccines for fear of neurotoxicity. The only problem that deserves attention is the suggested relationship between Al oxyhydroxide-containing vaccines and macrophagic myofaciitis or myalgic encephalomyelitis/chronic fatigue syndrome. Currently, definitive conclusions cannot be drawn on these risks and further studies must be conducted. Until then, Al remains the best solution to improve vaccine efficacy.