Predictors of hepatitis A vaccination among young children in the United States

We analysed data from the 2009 National Immunization Survey to determine potential predictors of hepatitis A vaccination coverage among children aged 19-35 months. Overall national coverage was 75% for ≥1 dose. Residence in a state with hepatitis A vaccination recommendations prior to 2006, or in a metropolitan statistical area within such state, or being a minority child were among the variables independently associated with higher vaccination coverage. While hepatitis A vaccination coverage has improved since nationwide routine childhood vaccination began in 2006, coverage remains lower than that for other recommended childhood vaccines.     

Antibody persistence and immune memory elicited by combined hepatitis A and B vaccination in older adults

Response to hepatitis A and B vaccines has been reported to decline with age. This open, prospective, single-site study examined the long-term response to the combined hepatitis A/B vaccine Twinrix in 98 primary responders aged 45-67 years. Levels of antibody against hepatitis A virus (HAV) and hepatitis B surface antigen (HBs) were tested 30 months after initial vaccination. At this stage, all participants remained seropositive for anti-HAV and 70% for anti-HBs. A booster vaccination was offered to those who had responded to the first vaccination but then lost protective levels of anti-HBs. An anamnestic response was observed in all cases.     

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 of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children

Hepatitis A and B vaccines are highly immunogenic in three-dose schedules. To obtain an equivalent result in children with two paediatric doses would be of significant benefit. The purpose of this study was to measure the immunogenicity of a two-dose schedule in children with two licensed recombinant HBsAg containing vaccines given at paediatric doses, one of them combined with hepatitis A. Seven-hundred and four healthy school children aged 8-10 years were recruited in an open label study to receive either Twinrix Pediatric (360 El.U HAV antigen; 10 microg HBsAg) or Recombivax (2.5 microg HBsAg) vaccine intramuscularly 6 months apart. The seroconversion (>/=1 mIU/ml for anti-HBs antibodies and >/=33 mIU/ml for anti-HAV antibodies), seroprotection (anti-HBs >/=10 mIU/ml) rates and the geometric mean titers (GMTs) were determined 4-8 weeks after the second dose. The anti-HBs seroconversion rate was 97.1% with Twinrix and 97.2% with Recombivax. The seroprotection rates were 96.5 and 94.4%, respectively (P = 0.17). The GMT was higher with Twinrix than with Recombivax (3248 mIU/ml versus 742 mIU/ml, P < 0.0001). All the children vaccinated with Twinrix seroconverted to HAV and the GMT was 5168 mIU/ml. The obtained results suggest that two paediatric doses of hepatitis vaccines are highly immunogenic in 8-10-year-old children. This schedule could facilitate a greater vaccine acceptance and the addition of hepatitis A vaccine to existing adolescent universal hepatitis B virus immunization programs.     

A combined dual-chamber typhoid/hepatitis A vaccine as a booster dose in hepatitis A primed adults

Vivaxim™ is a combined hepatitis A/typhoid fever vaccine (HA/Vi) licensed for vaccination of travellers, but long-term protection against hepatitis A requires two immunisations at least 6 months apart. A randomised, controlled study was performed in 116 healthy adults primed with hepatitis A vaccine (Avaxim™) to compare immune responses to HA/Vi and Avaxim™ given as booster doses 6 months later. Both vaccines elicited marked booster responses achieving antibody geometric mean titres (GMTs) of 4576 and 3760 mIU/ml in the HA/Vi and Avaxim™ groups, respectively. Although twice as frequent in the HA/Vi group, local reactions (mostly pain) were mainly mild and transient, probably reflecting the larger volume injected (1 ml). Vivaxim™ offers a convenient means of administering both HA and typhoid fever vaccines in subjects already primed for hepatitis A.     

The first combined vaccine against hepatitis A and B: an overview

Hepatitis A and B infections are prevalent world-wide and are a significant cause of morbidity and mortality. A vaccine providing dual protection against hepatitis A and B is now available (Twinrix, SmithKline Beecham Biologicals). Six pivotal vaccine trials, involving 843 healthy adults, aged between 17 and 60 years and vaccinated following a 0, 1, 6 month schedule are discussed. At month 2 more than 99% of the vaccinees were seropositive for anti-HAV and 84% were protected against hepatitis B. The third dose induced a 12-fold increase in geometric mean titres (GMTs) to 5404 mIU/ml. One month after completion of the vaccination course nearly all vaccinees had protective titres against hepatitis B with a GMT of 4818 mIU/ml. Long term follow-up data until month 48 is available for two studies. At month 48 all 129 vaccinees sampled were still positive for anti-HAV antibodies and > 95% were still protected against hepatitis B. The combined hepatitis A and B vaccine Twinrix proves to be consistently safe, well tolerated and highly immunogenic and compares well with serological responses reached with monovalent vaccines. This combined hepatitis A and B vaccine offers more convenience, potentially better compliance and lower administration costs.     

Combining hepatitis A and B vaccination in children and adolescents

Hepatitis A and B are common infections worldwide and their severity is related to the individual's age upon initial infection. Furthermore, when hepatitis B infection occurs in infants, the risk of becoming a chronic carrier is 90%. For hepatitis A, the lower incidence of disease arising from an improvement in living conditions leaves a greater number of children, adolescents and young adults susceptible to residual circulating virus. Consequently, initial infection occurs later in life when clinical illness is more frequent and the rate of morbidity and mortality higher. Although both viruses differ greatly, including their modes of transmission, the overlap in their epidemiology warrants the combination of hepatitis A and B vaccination. The immune response elicited by the combined hepatitis A and B vaccine following a three-dose schedule compares well with the anti-hepatitis A virus (HAV) and anti-hepatitis B sero-responses obtained with monovalent vaccines. In addition, it was shown that the seroprotection rate for anti-hepatitis B increased more rapidly with the administration of the combined vaccine, with values of more than 80% within 1 month after the first two doses (schedule, 0, 1 and 6 months). Currently, according to the World Health Organization recommendations, more than 116 countries are vaccinating their infants and/or adolescents against hepatitis B. Recently, several countries were considering or have decided to begin mass vaccination against HAV (more than fifteen states in the US, Spain (Catalonia), Italy (Puglia)). For these countries, the combination of hepatitis A and B antigens in one single vaccine offers the following advantages: fewer injections for protection against two infections, better compliance, lower implementation costs, and fewer missed vaccination opportunities. Further simplification of the schedule, by reducing the number of doses, would improve the compliance rate as well as being more convenient for the vaccinee. This should translate into a reduction in costs associated with vaccine administration. In some recent vaccine studies, the immunogenicity and safety profile of a two-dose schedule (0 and 6 months) of the adult formulation of the combined hepatitis A and B vaccine was investigated in children aged 1-11 years, as well as in adolescents aged 12-15 years. Current results indicate that this two-dose schedule of the adult formulation could be considered a viable alternative for immunization of children and adolescents.     

The effectiveness and safety of hepatitis A vaccine: a systematic review

We report on the conduct of a systematic review to assess the efficacy and the safety of hepatitis A vaccines in adults and children. We identified, retrieved, and assessed all trials evaluating the effects of hepatitis A vaccines on prevention of cases of hepatitis A, death from hepatitis A, and assessing nature and frequency of adverse events. We included eight randomised trials, four containing efficacy outcomes, three containing only safety outcomes and a single study containing efficacy and adverse events outcomes. Combined inactivated vaccine effectiveness was 86% (95% CI: 63-95%). Combined attenuated vaccine effectiveness was 95% (95% CI: 81-99%). Inactivated vaccine effectiveness in the prevention of HAV secondary cases, compared to non-intervention was 82% (95% CI: 23-96%). Safety profile of vaccines was similar to that of their comparators. Despite poor design and reporting of trials, we found convincing evidence of the effectiveness and safety of inactivated HAV vaccines.     

A prophylactic hepatitis B vaccine with a novel adjuvant system

Studies with recombinant hepatitis B vaccines show seroprotection rates varying between 91 and 100%. Thus, a limited risk may remain for non-responding populations (e.g. non-responders, haemodialysis patients, elderly) who could benefit from a more immunogenic hepatitis B vaccine. One strategy to enhance the immune response is the use of novel adjuvants. SmithKline Beecham has developed a new adjuvant system containing alum and 3-deacylated monophosphoryl lipid A: SBAS4 (SmithKline Beecham Adjuvant System 4). Pilot studies showed that SBAS4 improved in vivo humoral and in vitro cellular immune responses compared to the response to classical recombinant hepatitis B vaccines and was safe and well-tolerated. Several studies assessed the profile of the HBsAg/SBAS4 vaccine in a healthy population, non-responders or elderly. In general the HBsAg/SBAS4 vaccine was well tolerated. Compared to an established recombinant hepatitis B vaccine, we observed an increased local reactogenicity but few symptoms were reported as severe. The HBsAg/SBAS4 vaccine elicits a strong immune response: subjects are protected faster and the GMTs are usually much higher. HBsAg/SBAS4 thus has the potential to protect those subjects who fail to be protected by well established hepatitis B vaccines.     

Prevalence of indications for adult hepatitis A vaccination among hepatitis A outbreak-associated cases,Three US States, 2016–2019

BackgroundSafe and effective hepatitis A vaccines have been recommended in the United States for at-risk adults since 1996; however, adult vaccination coverage is low.MethodsAmong a random sample of adult outbreak-associated hepatitis A cases from three states that were heavily affected by person-to-person hepatitis A outbreaks, we assessed the presence of documented Advisory Committee on Immunization Practices (ACIP) indications for hepatitis A vaccination, hepatitis A vaccination status, and whether cases that were epidemiologically linked to an outbreak-associated hepatitis A case had received postexposure prophylaxis (PEP).ResultsOverall, 74.1% of cases had a documented ACIP indication for hepatitis A vaccination. Fewer than 20% of epidemiologically linked cases received PEP.ConclusionsEfforts are needed to increase provider awareness of and adherence to ACIP childhood and adult hepatitis A vaccination and PEP recommendations in order to stop the current person-to-person hepatitis A outbreaks and prevent similar outbreaks in the future.     

Combined hepatitis B vaccines

The status and likely impact of existing and potential new combined hepatitis B vaccines were broadly considered at the Viral Hepatitis Prevention Board (VHPB) meeting in Malta, October 2001. The currently available and/or licensed combined hepatitis B vaccines in Europe and the prospects for further such vaccines were reviewed. Data on the safety, immunogenicity, and European licensing status and availability of haxavalent vaccines combining hepatitis B (HepB), Haemophilus influenza type b (Hib), diphtheria, tetanus, and pertussis (acellular) (DTPa), and inactivated poliovirus (IPV) antigens were presented. Finally, the impact of the availability of combined hepatitis B vaccines on hepatitis B immunisation programmes in Europe were examined and the added value of combined hepatitis B vaccines globally was estimated.     

Comparison of the reactogenicity and immunogenicity of a two injection combined high-dose hepatitis A and hepatitis B vaccine to those of Twinrix

Twinrix (SmithKline Beecham Biologicals) is a combined hepatitis A and B vaccine licensed with a three-dose schedule. A two-dose combined hepatitis A and B vaccine would facilitate immunisation programs. In this prospective study, 100 healthy adults, aged between 18 and 40, were enrolled. A first group of 50 was given a high-dose vaccine at month 0 and 6. A second group of 50 received Twinrix at month 0, 1 and 6.The reactogenicity was assessed after each vaccine dose. There were no severe local adverse events. Seven severe systemic reactions occurred, of which five were fatigue, one was headache and one consist in gastrointestinal symptoms. They all resolved during the 4-day follow-up period. One serious general adverse event was reported, but was clearly unrelated to the vaccine. Thus, both vaccines were well tolerated.The immunogenicity was evaluated by testing for anti-HBs and anti-HAV antibodies. Seroconversion rates and geometric mean titres (GMTs) were compared. At month 7, the anti-HAV GMTs were higher in the high-dose group than in the Twinrix group and, inversely, the anti-HBs GMTs were slightly higher in the Twinrix group than in the high-dose group. At month 7, all subjects in both groups were positive for anti-HAV. All subjects in the high-dose group and 97.6% subjects in the Twinrix group had seroconverted for anti-HBs. Therefore, it can be concluded that with two injections of the high-dose hepatitis A and B vaccine, 6 months apart, a similar immune response can be obtained as induced with three doses of Twinrix at months 0, 1 and 6.     

甲型肝炎减毒活疫苗在甲型肝炎爆发中的保护效果

目的 探讨国产Ｈ２株甲型肝炎减毒活疫苗在甲型肝炎爆发中的保护作用。方法 疫苗接种采用非随机对照设计分组,以小学１～３年级及部分学前班儿童５５５１人为对象。效果考核采用流行病学和血清学分析,抗－ＨＡＶ ＩｇＭ检测采用ＥＬＩＳＡ法。结果 疫苗接种１年后发生甲型肝炎爆发,观察对象中发生２６例甲型肝炎,相关村疫苗组发病率０．２８％（１／３５６）,对照组发病率５．９２％（２５／４２２）,疫苗保护率９５．２７     

World-wide control of hepatitis B

It has been 30 years since the Third World Health Assembly convened a WHO Expert Committee to consider investigation, control, and prevention of viral hepatitis. During that time, significant advances have been made in understanding the etiology and epidemiology of viral hepatitis. Technological advances of the 1970s enabled widespread rapid diagnosis and the development of vaccines of high efficacy. These advances have allowed the implementation of control programs on a global scale. Because liver cancer (PHC) is among the 10 most common cancers in the world, the link between PHC and viral hepatitis is important. Up to 80% of these cancers are attributable to the hepatitis B virus. Although the development of PHC is not associated with acute hepatitis B virus itself, the chronic HBV carrier state may be classified as a precancerous lesion. Task forces have been convened consider implementation of hepatitis control programs, especially in countries where the infection is hyperendemic. The most important prevention method is active immunization, but vaccination strategies must consider differences in geographical patterns of prevalence. In areas of low endemicity, such as North America, Western Europe, and Australia, immunization of selected high risk groups is suggested. In areas of high endemicity, such as sub-Saharan Africa, southeast Asia, and China, large-scale vaccination of infants is recommended, similar to DPT and polio vaccination programs. Current hepatitis B vaccines are favorable to mass infant immunization because of their high tolerability, excellent immunogenicity, and their ability to induce primary humeral antibody response. However, these vaccines are available in insufficient quantities and the costs are too high for use on a large scale. Newer vaccines, based on recombinant DNA techniques (rather than plasma-derived vaccines) show promise in increasing the quantity and reducing the cost of hepatitis B vaccines.     

Comparison of two combined vaccines against typhoid fever and hepatitis A in healthy adults

A prospective, randomised, observer-blind, comparative study was performed in healthy adults with a new hepatitis A/typhoid combined vaccine, Viatim, and the marketed Hepatyrix vaccine. Both vaccines induced high levels of protective antibodies, but typhoid responses were higher and hepatitis A responses more rapid with Viatim compared with Hepatyrix. Both vaccines were well tolerated, no serious adverse events (SAEs) occurred, but more Viatim vaccinees had more mild or moderate local reactions (82.7%) than Hepatyrix (53.1%, p < 0.001). In this direct comparison Viatim induced more local reactions, but elicited a more rapid and higher immune response to both antigens than Hepatyrix.     

Viral hepatitis

Three forms of viral hepatitis can be recognized: hepatitis A, hepatitis B, and hepatitis non-A, non-B. Hepatitis A is caused by a picornavirus, is transmitted by the faceal—oral route, does not become chronic, and no chronic virus carriers exist. The virus can be grown in cell cultures, and killed as well as live attenuated virus vaccines are under development. Hepatitis B is caused by an enveloped virus containing a circular, double-stranded form of DNA. The disease is transmitted parenterally through inoculation of blood or blood products containing virus or through close personal contact with a virus-positive person. Hepatitis B becomes chronic in a certain number of cases and can lead to cirrhosis and primary liver cell carcinoma. The blood and certain body secretions of individuals with a persistent or chronic infection may remain infectious for many years. The hepatitis B virus cannot be grown in cell cultures but the entire genome has been sequenced and cloned in bacterial and eukaryotic cells. An inactivated virus vaccine has been prepared from hepatitis B surface antigen present in the plasma of hepatitis B virus carriers and further vaccines are under development. The agents of hepatitis non-A, non-B have not been identified. It is possible to distinguish between a predominantly parenterally transmitted and an orally transmitted form of hepatitis non-A, non-B. The latter is reported to be caused by a picornavirus that does not, however, have any antigenic relationship with hepatitis A virus.     

A hepatitis B vaccine formulated with a novel adjuvant system

Although more than 95% of the vaccinated population responds to the currently licensed vaccines against hepatitis B, some groups were found to be low responders. Lipid A as adjuvant, through its ability to activate macrophages, might improve humoral as well as cellular immune response. Therefore we evaluated the profile of a hepatitis B vaccine with the new adjuvant system SBAS4. 150 young adults were enrolled and randomized into three groups: one received the SBAS4 hepatitis B vaccine, the second Engerix-B(TM) and the third a hepatitis B vaccine with an alternative formulation on alum. Vaccinations were at 0 and 6 months. The vaccine was well tolerated. At month 7 all vaccinees were protected but with significant differences in GMTs between groups: 13,271 mIU/ml for the SBAS4 group versus 1203 and 1823 mIU/ml. Hence the hepatitis B vaccine with the new adjuvant system is more immunogenic compared to the other vaccines containing the same antigen and could be suitable for a two dose schedule.     

Comparison of two combined vaccines against typhoid fever and hepatitis A in healthy adults

A prospective, randomised, observer-blind, comparative study was performed in healthy adults with a new hepatitis A/typhoid combined vaccine, Viatim™, and the marketed Hepatyrix™ vaccine. Both vaccines induced high levels of protective antibodies, but typhoid responses were higher and hepatitis A responses more rapid with Viatim™ compared with Hepatyrix™. Both vaccines were well tolerated, no serious adverse events (SAEs) occurred, but more Viatim™ vaccinees had more mild or moderate local reactions (82.7%) than Hepatyrix™ (53.1%, p < 0.001). In this direct comparison Viatim™ induced more local reactions, but elicited a more rapid and higher immune response to both antigens than Hepatyrix™.     

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals) compared with simultaneous administration of the two corresponding monovalent vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS: At month 1, 100% of subjects in the combined group and 99% of the controls were seropositive for anti-HAV antibodies. The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95% confidence intervals (CIs) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2% in the combined group and 95% in the control group. For anti-HBs, this was 94 and 91.6%, respectively. All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre was 26002 and 29,196mIU/ml, respectively. Both groups had a similar reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation.     

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.