Antibody avidity measurements in recipients of Cervarix vaccine following a two-dose schedule or a three-dose schedule

The HPV-16/18 vaccine (Cervarix^®) is a prophylactic vaccine for the prevention of cervical cancer and contains recombinant virus-like particles (VLPs) assembled from the L1 major capsid proteins of human papillomavirus (HPV) strains 16 and 18. Although a correlate of protection has yet to be identified, HPV-specific antibodies are thought to prevent virus infection of the genital mucosa. Therefore, antigen-specific antibodies as assessed by ELISA or pseudovirion-based neutralisation assay are frequently measured in clinical trials to substantiate the immune responses induced by the vaccine. Measuring antigen-antibody binding avidities, which reflects the degree of affinity maturation in the B-cells, is another valuable method to assess the quality of the antibody responses. Here we describe the antigen-specific antibody avidities in samples taken from a clinical trial examining the feasibility of adopting a two-dose (Months 0 and 6) schedule for 9–14 year olds instead of the three-dose schedule (Months 0, 1 and 6). Antibody avidity (i.e. avidity index [AI]) was determined in the ELISA by the ratio of antibody concentrations in serum samples treated or not with the chaotropic agent NaSCN. Importantly, in the comparison between the groups of two-dose and three-dose recipients, no differences in AIs were observed at Months 7, 24 and 48. The results suggest that from Month 7 to 48, the quality of the antibody response in terms of avidity was similar in the two-dose recipients to that in the three-dose recipients. Hence these results support the adoption of a two-dose schedule in 9–14 year-old girls.     

Impact of a statewide childhood vaccine program in controlling hepatitis A virus infections in Alaska

Historically, Alaska experienced cyclic hepatitis A virus (HAV) epidemics, and the HAV rate among Alaska Native people was significantly higher than among other racial/ethnic groups. We evaluated the impact of universal childhood vaccination, initiated in 1996, on HAV epidemiology in Alaska by analyzing HAV cases reported to the State of Alaska. HAV incidence in all age groups declined 98.6% from 60.0/100,000 in 1972–1995 to 0.9/100,000 in 2002–2007. The largest decrease (99.9%) was in Alaska Native people, whose incidence (0.3) in 2002–2007 was lower than the overall U.S. 2007 rate (1.0). Among age groups, the decrease (99.8%) among children aged 0–14 years was the largest. Routine childhood vaccination has nearly eliminated HAV infection in Alaska.     

Development of duck hepatitis A virus type 3 vaccine and its use to protect ducklings against infections

A variant type of duck hepatitis A virus (DHAV), DHAV-3 was recently discovered in South Korea and China. Sequence analyses verified that the variant is genetically or serologically different from the DHAV-1 and DHAV-2 types. Duck hepatitis had been reported in South Korea since 1985 and an attenuated DHAV-1 vaccine had efficiently prevented epidemics of DHAV-1 until 2002. Despite the DHAV-1 based vaccine in use the novel DHAV-3 circulating in South Korea remains to be a threat to duckling farming. To develop a live attenuated vaccine against DHAV-3, a representative isolate, AP-04203, was therefore attenuated by repeated passages in SPF chicken embryos 100 times. The 100th passaged virus, AP-04203P100, did not cause clinical sign and mortality in 1-day-old ducklings as well as reversion of virulence capacity. The ducklings vaccinated with AP-04203P100 virus (10^3.0 ELD₅₀/0.2 ml) on 1-day-old age via the intramuscular injection were well protected from 2 days after challenge with pathogenic AP04203P1 virus via the intramuscular route. In addition, the vaccine candidate also exhibited complete protection against currently circulating pathogenic DHAV-3 isolates.     

Reduced detection and levels of protective antibodies to hepatitis B vaccine in under 2-year-old HIV positive South African children at a paediatric outpatient clinic

The study evaluated and compared the prevalence of anti-HBs and exposure to hepatitis B virus (HBV) in vaccinated South African babies aged between 5 and 24 months from the Expanded Programme on Immunisation clinic [EPI group] and paediatric outpatient clinic [OPD group], and results were stratified by HIV status. A total of 303 (243 EPI group and 60 OPD group) babies were studied. All sera were tested for anti-HBs, HBsAg and anti-HBc, while IgM anti-HBc and HBV DNA were only tested in samples positive for HBsAg and/or anti-HBc. Overall, there was a gross difference in the prevalence of anti-HBs marker between the EPI and OPD groups. The EPI group demonstrated higher levels of seroconversion (89.3% vs. 81.7%; p=0.105) and seroprotection rates (86.0% vs. 75.0%; p=0.038), compared to the OPD babies. When the overall results were stratified by HIV status, seroprotection was 85.7% for the HIV-negatives and 78.1% for the HIV-positives, although this was not statistically significant (p=0.125). The seroprotection rates were almost comparable between the HIV-positives (84.3%; n=51) and the HIV-negatives (86.5%; n=192) (p=0.695) in the EPI group. In contrast, reduced seroprotection rates were observed between the HIV-positives (63.6%; n=22) and HIV-negatives (81.6%; n=38) in the OPD group, although this was not statistically significant (p=0.123). Interestingly, no HBsAg or anti-HBc marker was detected in the OPD group, compared to total exposure rate of 4.9% (HBsAg carriage was 1.2%) in the EPI group.     

Long-term protection provided by hepatitis B vaccine and need for booster dose: A meta-analysis

The duration of protection provided by hepatitis B vaccine is still unknown but can be estimated through long-term follow-up studies. Electronic databases and conference databases to December 2008 were searched. Reference lists of articles were screened and the studies authors and manufacturers were contacted for additional unpublished references. Randomized clinical trials and prospective cohort studies addressing the long-term protective effect of hepatitis B vaccine were included in this meta-analysis. We assessed 42 separate cohorts involving overall 11,090 subjects; 34 cohorts involving 9356 subjects were included in the final meta-analysis. Results indicate that the overall cumulative incidence of HBV breakthrough infection 5–20 years post-primary vaccination was 0.007 [95% CI: 0.005 to 0.010] with a variation among studies from 0 to 0.094. Available data do not allow us to exclude an increased risk for infection with time since vaccination. We conclude that the protection provided by three or four doses of monovalent HB vaccine persists for at least two decades in the great majority of immunocompetent individuals. Additional studies are needed for assessing vaccine efficacy for longer periods of time and the need of booster doses in different subgroups of population.     

Model based estimates of long-term persistence of inactivated hepatitis A vaccine-induced antibodies in adults

Background

In this paper, we review the results of existing statistical models of the long-term persistence of hepatitis A vaccine-induced antibodies in light of recently available immunogenicity data from 2 clinical trials (up to 17 years of follow-up).

Methods

Healthy adult volunteers monitored annually for 17 years after the administration of the first vaccine dose in 2 double-blind, randomized clinical trials were included in this analysis. Vaccination in these studies was administered according to a 2-dose vaccination schedule: 0, 12 months in study A and 0, 6 months in study B (NCT00289757/NCT00291876). Antibodies were measured using an in-house ELISA during the first 11 years of follow-up; a commercially available ELISA was then used up to Year 17 of follow-up. Long-term antibody persistence from studies A and B was estimated using statistical models for longitudinal data. Data from studies A and B were modeled separately.

Results

A total of 173 participants in study A and 108 participants in study B were included in the analysis. A linear mixed model with 2 changepoints allowed all available results to be accounted for. Predictions based on this model indicated that 98% (95%CI: 94–100%) of participants in study A and 97% (95%CI: 94–100%) of participants in study B will remain seropositive 25 years after receiving the first vaccine dose. Other models using part of the data provided consistent results: ≥95% of the participants was projected to remain seropositive for ≥25 years.

Conclusion

This analysis, using previously used and newly selected model structures, was consistent with former estimates of seropositivity rates ≥95% for at least 25 years.     

Immune response to hepatitis B vaccine with high antigen content in non-responders after standard primary vaccination in Chinese adults

Context

Alternative schedules are needed to provide greater immunogenicity in adults who fail to respond to the standard hepatitis B (HB) vaccine regimen.

Objective

To evaluate the immunogenicity and safety of high antigen content HB vaccine formulations administered to non-responders after routine primary vaccination.

Design setting, and participants

This was a phase III, double-blind, controlled clinical trial in China. We enrolled healthy participants (16–60 years old) seronegative for HB surface (HBs) antigen after primary vaccination, who had HBs antibody (anti-HBs) titres <10 mIU/ml at 28 days following routine vaccination with licensed HB vaccine containing 10 μg of antigen. Participants were randomised (2:2:1) to receive three booster doses of HB vaccine formulations containing 60 μg, 30 μg or 10 μg of antigen per dose 28 days apart. Blood samples were obtained pre-vaccination and 28 days after each dose to assess immunogenicity. Reactogenicity and safety were evaluated up to 28 days after each vaccine dose.

Results

Seroconversion rates were ≥92.1% and ≥87.1% as from the second dose of the 60 μg and 30 μg HB vaccine formulations, respectively, with geometric mean concentrations (GMCs) of ≥286.0 mIU/ml and ≥164.0 mIU/ml. In the 10 μg HB vaccine group the seroconversion rates were ≥83.0% and the GMCs ≥110.1 mIU/ml as from the second vaccine dose. All HB vaccine formulations were well tolerated: 352/1091 (32.3%) participants reported at least one injection-site or systemic adverse reaction (145/434 [33.4%] from the 60 μg group; 138/435 [31.7%] from the 30 μg group and 69/222 [31.1%] from the 10 μg group). Most reactions were mild or moderate and resolved within 24 h. No serious adverse events were reported.

Conclusion

Booster vaccination with a three-dose schedule of a high antigen content HB vaccine formulation was immunogenic and well tolerated in healthy adults.

Clinicaltrials.gov identifier

NCT01203319.     

Two decades of hepatitis B vaccination in mentally retarded patients: effectiveness, antibody persistence and duration of immune memory

Introduction

Institutionalized mentally retarded subjects are well-known to be at-risk for HBV infection. We studied the persistence of vaccine-induced anti-HBs antibodies and the robustness of the HBsAg-specific immune memory in this population, 18–20 years after the first vaccine dose.

Materials and methods

Non-immune residents of 4 institutions were immunized in 1984–1986. In 2004, 207 subjects were bled to determine humoral and cellular immune memory. Immune response to a booster dose was evaluated in subjects with anti-HBs level <100 IU/L.

Results

Four subjects showed anti-HBc seroconversion, without clinical implications. Pre-booster anti-HBs levels <100 IU/L were found in 45 subjects (22%); 34/39 (87%) responded with a rapid and high anti-HBs titer to the booster dose. Robust T and B cell memory was present pre- and post-booster.

Discussion and conclusion

Overall results confirm that hepatitis B vaccines are highly effective and immunogenic, and confer long-term persistence of antibodies and immune memory in an at-risk population.     

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates

Background

A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants.

Methods

Healthy 1–10-day-old neonates (N = 566) received 3 intramuscular doses (5 μg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10 mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1–14.

Results

Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7 mIU/mL for the mpHBV group and 670.1 mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs.

Conclusions

The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority.     

Cost-effectiveness of hepatitis B vaccination using HEPLISAV™ in selected adult populations compared to Engerix-B vaccine

Objective

HEPLISAV™ is an adult hepatitis B vaccine that requires fewer doses over a shorter period of time and elicits higher and earlier seroprotection compared to Engerix-B to reduce the risk of hepatitis B infection. The objective of this analysis was to evaluate the cost-effectiveness of vaccination with HEPLISAV vs. Engerix-B^® to prevent hepatitis B infection in select populations.

Methods

Markov models were developed for the following populations: diabetics, patients with chronic or end stage kidney disease, healthcare workers and international travelers to countries with high HBV infection prevalence. Hepatitis B disease progression was modeled using 11 health states: seroprotected, susceptible, acute infection, chronic infection, fulminant hepatic failure, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-transplant care, and death. Seroprotection rates were obtained from two phase 3 clinical trials comparing HEPLISAV with Engerix-B and ranged across various populations from 89–96% for HEPLISAV and 62–81% for Engerix-B. Higher vaccination completion rates were assumed for HEPLISAV compared with Engerix-B given that fewer doses of HEPLISAV are required in a shorter period of time to achieve seroprotection for the evaluated populations. Each cycle length after the first year in the model was 1-year. All future costs and benefits were discounted at 3%. A lifetime analysis and a U.S. payer perspective were used.

Results

HEPLISAV has a favorable cost-effectiveness profile with incremental cost effectiveness ratios <$25,000 across all populations studied. In the patients with chronic or end stage kidney disease, HEPLISAV was the dominant option and was cost-saving compared with Engerix-B. The cost of vaccine, regimen completion rates, and seroprotection rates were the sensitive variables in the models.

Conclusions

HEPLISAV is a cost-effective option to provide high rates of seroprotection and early seroprotection across a range of populations from health care workers to patients with chronic or end stage kidney disease.     

Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine

BackgroundThe exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence.MethodsSubjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12–15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11–15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: <15 mIU/mL; anti-HBs: <10 mIU/mL).Results209 subjects returned for follow-up at Year 15 of whom 162 were included in the long-term according-to-protocol immunogenicity cohort. All subjects remained seropositive for anti-HAV antibodies, while 81.1% and 81.8% still had anti-HBs antibodies ≥10 mIU/mL in the 2- and 3-dose groups, respectively. Following hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience.ConclusionImmunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination.Trial registrationhttp://www.clinicaltrials.gov NCT00875485.     

Evaluating functional antibodies in rhesus monkeys immunized with hepatitis B virus surface antigen vaccine with novel adjuvant formulations

Effective and safe novel adjuvants are of great interest to the vaccine research community. In this study, we describe our evaluation of adjuvant formulations containing a TLR9 agonist adjuvant (ISS1018) or ISCOMATRIX™ adjuvant for a two-dose regimen of hepatitis B virus surface antigen virus-like particle vaccine in mice and rhesus macaques. Our results show a 10-20 fold improvement in Ab binding titers determined in an antigen-sandwich assay for adjuvant formulations with ISCOMATRIX™ adjuvant, in comparison to routine aluminum formulation. Furthermore, we optimized a competition assay to evaluate a functional component of immune sera, using a conformation-dependent and protective mAb, RFHBs1, as the probe. Although good correlation was observed between Ab binding titers from the antigen-sandwich assay and functional titers from the in-solution competition against RFHBs1, the latter assessment provided a much more stringent ranking of adjuvant formulations than the former. These results indicate the importance of evaluating functional Abs when assessing and comparing novel adjuvant formulations, as it provides another angle to investigate the effects of change in adjuvant composition on antigenic integrity of the testing vaccines.     

甲、乙型肝炎联合疫苗在儿童中0、6月程序接种的安全性和免疫原性研究

目的 观察和评价在儿童中接种2剂倍尔来福~(TM)甲、乙型肝炎(分别简称为甲肝、乙肝)联合疫苗的安全性及免疫原性.方法 本研究以江苏省常州市116名1～10岁完成乙肝疫苗全程免疫同时无甲肝疫苗接种史的抗甲肝病毒抗体(anti-hepatitis A virus,抗-HAV)阴性儿童为研究对象,按0、6个月程序接种甲、乙肝联合疫苗(倍尔来福~(TM)).每剂疫苗0.5 ml,含HAV抗原250 U和乙肝表面抗原5μg.观察接种疫苗后72 h内局部反应和全身反应,检测免疫后1、6、7个月的血清抗-HAV阳转率、乙肝病毒表面抗体(抗-HBs)保护率及抗体滴度.结果 倍尔来福~(TM)接种后局部和全身不良反应发生率分别为12.1%(14/116)和6.0%(7/116),其中局部不良反应以注射部位红、肿、硬结为主,占6.9%(8/116)～11.2%(13/116),全身不良反应发生率为6.0%(7/116),以发热为主.免疫后1、6、7个月,抗.HAV阳转率为92.9%(92/99)～100.0%(101/101),抗体几何平均滴度(GMT)为47.0～2762.3 mIU/ml;疫苗免疫前抗-HBs阳性保护率为86.1%(87/101),免疫后1个月达到100.0%(101/101),免疫后1、6、7个月抗-HBs GMT为894.3～3314.3 mlU/ml.结论 倍尔来福~(TM)甲、乙肝联合疫苗2剂接种程序在乙肝基础免疫儿童中应用具有良好的安全性和免疫原性.     

Safety and immunogenicity of the pneumococcal pneumolysin derivative PlyD1 in a single-antigen protein vaccine candidate in adults

Background

Pneumococcal vaccines based on conserved protein antigens have the potential to offer expanded protection against Streptococcus pneumoniae.

Objective

This study examined the safety and immunogenicity in adults of three doses of a pneumococcal single-antigen protein vaccine candidate formulated with aluminum hydroxide adjuvant and recombinantly derived, highly detoxified, genetically mutated pneumolysin protein (PlyD1).

Methods

This phase I, randomized, placebo-controlled, observer-blinded, dose-escalating study enrolled adults (18–50 years). In a pilot safety study, participants received a single injection of 10 μg PlyD1 and were observed for 24 h. Following review of the pilot safety data, participants were randomized (2:1) to receive two injections of PlyD1 at one of three doses or placebo 30 days apart. Assignment of second injection and successive dose cohorts was made after blinded safety reviews after each injection at each dose level. Safety endpoints included rates of solicited injection site reactions, solicited systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included geometric mean concentrations of anti-PlyD1 IgG as determined by ELISA and functional assessment in an in vitro toxin neutralization assay.

Results

The study included a total of 100 participants, including 10 in the pilot study and 90 in the randomized study. None of the participants in the pilot study had SAEs, allergic reactions, or other safety concerns. Ninety participants received two doses of or placebo (n = 30) or active vaccine candidate at 10 (n = 20), 25 (n = 20), or 50 μg (n = 20). No vaccine-related SAE or discontinuation due to an AE occurred. Most solicited reactions were mild and transient. The most frequently reported solicited reactions were pain at the injection site and myalgia. Antigen-specific IgG levels and functional activity showed dose-related increases. When comparing the three dose levels, a plateau effect was observed at the 25 μg dose.

Conclusions

All dose levels were safe and immunogenic. Repeat vaccination significantly increased the level of anti-PlyD1 antibodies. Functional antibody activity was demonstrated in sera from vaccinated individuals (ClinicalTrails.gov no. NCT01444352).     

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls

Background

To evaluate co-administration of GlaxoSmithKline Biologicals’ human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).

Methods

This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n = 247), HepB (n = 247) or HPV co-administered with HepB (HPV + HepB; n = 247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort.

Results

The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10 mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated.

Conclusions

The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years.

Clinical trials registration

ClinicalTrials.gov registration number NCT00652938.     

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy

Introduction

HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired.

Methods

We analysed the response to vaccination (antiHAV titres ≥20 IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression.

Results

The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05–0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14–0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3–10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22–5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48–3.63).

Conclusion

The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers.     

国产甲乙型肝炎联合疫苗的安全性和免疫原性初步研究

目的评价国产甲、乙肝联合疫苗的安全性和免疫原性。方法对278名健康儿童和312名健康成人接种国产甲、乙肝联合疫苗，并与单价甲肝灭活疫苗和乙肝灭活疫苗进行对照，观察其免疫后的副反应和检测抗体阳转率。结果接种国产甲、乙肝联合疫苗成人和儿童中均未观察到严重全身反应和局部反应。首针免疫后7个月，儿童组甲肝抗体和乙肝抗体阳转率分别达到100％和96．88％，GMT达到29144mIU／ml和102mlU／ml；成人组甲肝抗体和乙肝抗体阳转率也达到100％和98．84％，GMT达到21891mIU／ml和112mlU／ml。儿童和成人接种甲乙肝联合疫苗后，甲肝和乙肝抗体阳转率和GMT均高于单价疫苗。结论国产甲、乙型肝炎联合疫苗是安全的，并可诱导较高的甲肝抗体和乙肝抗体应答。     

孩尔来福甲型肝炎灭活疫苗0,12个月免疫程序研究

目的　对孩尔来福 (HealiveR○)甲型肝炎 (甲肝 )灭活疫苗的安全性、免疫原性及适宜儿童的剂量进行研究。方法　在某山区两个农村筛选 4～ 10岁甲肝病毒抗体 (抗 HAV)阴性的 85名易感儿童。以自然村随机分为两组 ,按 0 ,12个月免疫程序分别接种北京科兴生物制品有限公司生产的每剂 2 50U 0 .5ml和 50 0U 1ml甲肝灭活疫苗 ,观察免疫后局部反应和全身反应 ,检测初次免疫 (初免 )后 2 1天、12个月及全程免疫后 1个月抗 HAV阳转率和抗体几何平均滴度 (GMT )。结果　两组均未见严重局部反应和全身反应 ;2 50U 0 .5ml组和 50 0U 1ml组初免后 2 1天 ,抗 HAV阳转率分别为94.4%和 10 0 .0 % ,GMT分别为 195mIU ml和 3 70mIU ml ;初免后 12个月抗 HAV全部阳转 ,GMT分别达 3 61mIU ml和 456mIU ml(P >0 .0 5) ;全程免疫后 1个月 ,GMT分别达 14 893mIU ml和2 1696mIU ml。结论　孩尔来福甲肝灭活疫苗的安全性和免疫原性好 ;每剂 2 50U 0 .5ml适宜儿童 ;0 ,12个月免疫程序更适宜中国儿童     

Evaluation of immune responses to combined hepatitis A and B vaccine in HIV-infected children and children on immunosuppressive medication

Objective

A phase IV interventional study with a combined hepatitis A and B vaccine was conducted in HIV-infected children and children receiving immunosuppressive medication for treatment of rheumatic diseases to evaluate immune responses.

Methods

Both groups (1–16 years of age) received combined (inactivated) HAV and (rDNA) HBV vaccine Ambirix^® at months 0 and 6. Serum samples were taken at four time points and tested for anti-HAV and anti-HBs antibodies. Anti-HAV concentrations ≥20 mIU/mL or anti-HBs concentrations ≥10 mIU/mL were considered protective. Seropositivity percentages were calculated and geometric mean concentrations (GMCs) were compared by nonparametric Mann–Whitney U-test or Kruskal–Wallis one-way-analysis-of-variance.

Results

Of 80 HIV-infected children who completed the study, 67 were HAV-susceptible and 68 HBV-susceptible at enrolment. Of 80 children with rheumatic diseases who completed the study, 65 were HAV-susceptible and 74 HBV-susceptible at enrolment. Immune responses to HAV after first dose of vaccine in both study groups were low: 71% and 55% respectively, whereas immune responses after the second dose were 99% and 100% respectively. Immune response to HBV after first dose of vaccine in both groups was also low: 27% and 17% respectively. Immune responses after the second dose were 97% and 93%, respectively. A larger proportion of children on combination antiretroviral therapy (cART) and of children with viral load <50 copies/mL responded to HBV, and also showed a significantly higher GMC.

Conclusions

Although immune response after full series of combined HAV and HBV vaccine in both groups was excellent and comparable to healthy children, a substantial proportion of both groups was not protected for HAV after first dose of vaccine. This protection gap is especially important for HAV in travel health and postexposure prophylactic treatment: both groups of children should be serologically tested for anti-HAV prior to travel to ensure protection if there is no time to await second dose of vaccine.     

Shifts in the rates and levels of antibody to hepatitis A virus associated with hepatitis A infection in children's communities

In order to investigate the shift in the rates and levels of antibody to hepatitis A virus, 567 children in 20 isolated groups of five day-care centers were observed over a period of 8 months during which the seasonal rise in hepatitis A morbidity occurs. Increases in the proportion of seropositive ranging from 5 to 37% were demonstrated in 6 groups, and were always associated with the occurrence of either overt or sub-clinical hepatitis A infection. High rates of seropositivity were also noted in the groups in which cases of hepatitis A had been registered prior to the period of observation. In some children with low and medium antibody levels, antibody titres showed further increases after reinfection. A substantial part of children retained low antibody titres during the entire period of observation, and eight previously sero-negative children developed low antibody levels after asymptomatic hepatitis A infections. In one group the spread of hepatitis A infection (clinical and asymptomatic) was prevented by the administration of commercially available immunoglobulin immediately after the discovery of an infected food handler. Passive antibodies were found in previously sero-negative children, and these antibodies dropped to undetectable levels two months after administration.