An open-label randomized study was undertaken to compare a 2-dose regimen (Months 0 and 6) of hepatitis B surface antigen (HBsAg) vaccine formulated with a novel adjuvant (HBsAg/AS04) with a standard 3-dose regimen (Months 0, 1 and 6) of licensed recombinant HBsAg vaccine in terms of immunogenicity and reactogenicity when administered to healthy subjects aged between 15 and 40 y. At 1 and 6 months after the full vaccination course there was a 100% seroprotection rate (anti-HBs > or = 10 mIU/ml) with the HBsAg/AS04 vaccine, compared with a 99% response rate with the licensed vaccine. The corresponding geometric mean titres were significantly higher for the novel vaccine compared to the standard vaccine: 15,468 and 2,745 mIU/ml at Months 7 and 12 vs. 6,274 and 1,883 mIU/ml, respectively. There was a higher prevalence of local symptoms with the adjuvant vaccine (90% of doses) than with the standard vaccine (48% of doses). However, these symptoms (pain, swelling and redness) were predominantly of mild-to-moderate intensity and resolved rapidly without treatment. A 2-dose regimen of the new HBsAg/AS04 adjuvant vaccine therefore compared favourably to the standard regimen in healthy young adults. It is anticipated that the simplified vaccination schedule may improve compliance and reduce costs.
Few data are available concerning the persistence of anti-HBs and the effect of booster doses given several years post-vaccination against hepatitis B during preadolescence. The objective of this open-labelled clinical trial was to evaluate the persistence of antibodies after vaccination with three paediatric doses of Engerix-B at the age of 8-10 years and the effect of a booster dose given 5 (Group Y5) or 10 (Group Y10) years later. Anti-HBs were measured before and one month post-primary vaccination, then 5 and 10 years later, before the booster dose, as well as one month and 1 year post-booster. The anamnestic response was defined as a >or=fourfold increase of anti-HBs post-booster (>or=10 IU/L) when compared to pre-booster. Ten years post-primary vaccination, 559 of the 652 initially randomized subjects (86%) were eligible for analysis. Group Y5, 5 years post-booster results: 99% of subjects had detectable levels of antibodies and 96% a titer >or=10 IU/L. The anti-HBs GMTs decreased from 114,489 IU/L one month post-booster to 3354 IU/L 5 years later. Group Y10 results: 10 years post-primary vaccination 96% of subjects had a detectable level of anti-HBs and 85% were above the threshold of 10 IU/L. The GMTs one month post-booster were 31,030 IU/L. The challenge with a booster demonstrated an anamnestic response in 99% of subjects in group Y5 and 100% of subjects in group Y10. All subjects were anti-HBc negative. The booster doses were well tolerated. The excellent anamnestic response observed after the booster dose demonstrates the persistence of immunity in virtually all young adults vaccinated at the age of 8-10 with three paediatric doses of Engerix-B.
To assess a hepatitis B vaccination program offered to all grade 6 students in British Columbia in 1992.
British Columbia, Canada.
All grade 6 students were offered vaccine. Subsets of 454 and 259 students participated in studies of minor adverse events and seroresponse, respectively.
The vaccine used was Engerix-B, 20 micrograms, given at intervals of 0, 1, and 6 months.
Province-wide acceptance and series completion rates and reports of severe adverse events. Minor adverse events and immunogenicity in subsamples.
A total of 127,922 vaccine doses were administered. Initial enrollment totaled 43,358 students or 95.4% of those eligible. The series was completed by 41,594 students (95.6%). Minor adverse events were infrequent in the cohort assessed: no absenteeism or physician visits resulted from vaccination. Sixty-nine reported severe adverse events met surveillance definitions, the major categories being injection site reactions (23% of reports), fainting (20%), and rashes (17%). There was one instance of anaphylaxis. Only 13 of these events resulted in recommendations to discontinue the series. Of students tested following the series, 98% had levels of antibody to hepatitis B surface antigen considered to be protective (> or = 10 IU/L), the geometric mean titer being 690 IU/L (95% confidence interval, 498 to 957 IU/L).
Our experience indicates that school-based programs for universal vaccination of preadolescents can be highly acceptable and efficient.
Comment In: JAMA. 1995 Oct 18;274(15):1242-37563516
The aim of our analysis was to investigate the association between acculturation and the vaccination coverage among pre-school children.
We performed a study of vaccination status for measles-mumps-rubella and hepatitis B among pre-school children, during mandatory school entry examinations, in a district of Bavaria, Germany, in 2004 and 2005 (N = 2,043). Prior to the examinations, parents were asked to fill out a self-administered questionnaire assessing socio-demographic information, including variables related to migration background (response rate 73%, N = 1,481). We used Categorical Principal Component Analysis (CATPCA) to create an acculturation index and assessed the association between the acculturation and vaccination status for both vaccines.
We found no difference in vaccination status with the measles-mumps-rubella vaccine in relation to acculturation. The coverage with at least three doses of hepatitis B vaccine was similar among migrants and in the indigenous population, but the risk of incomplete (1 or 2 doses) versus full vaccination was higher (OR = 2.74, 95% CI 1.34-5.61) and the risk of lacking vaccination lower (OR = 0.30, 95% CI 0.12-0.77) among less acculturated migrants compared to the indigenous population.
For multi-dose vaccines lower acculturation was associated with incomplete vaccination, but the partial protection in this group was higher compared to indigenous population.
Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, we investigate the relationship between prior clinical infection or vaccination and the risk of MS.
Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls.
Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p
The aim of the study was to find out why there was a low attendance at a vaccination campaign against hepatitis B carried out amongst hospital staff in Copenhagen (Bispebjerg Hospital). An anonymous questionnaire was sent to 653 employees in June 1991. Subjects were asked to describe occupational percutaneous and mucocutaneous blood exposure and vaccination status, as well as why they had not become vaccinated. Three hundred and forty-three (51%) subjects responded. Sixty percent had been exposed to blood during the last six months, especially doctors (79.6%), both physicians and surgeons, registered nurses (66.7%) and laboratory technicians (39.4%). Sixty-seven percent had started vaccination against hepatitis B and 86.7% had completed three vaccinations. Reasons not to become vaccinated were: afraid of secondary effects, doubt about the security of the vaccine, didn't receive any offer of vaccination, low risk of blood exposure and had not thought about it. In conclusion, a lot of hospital staff members have a high risk of blood exposure and thus possibility of infection with a blood-transmitted disease. Information about hepatitis B and information about the vaccine is important. All doctors, both physicians and surgeons, ought to be vaccinated against hepatitis B. Instructions against blood exposure need to be repeated over and over again.
Denmark is a country with low prevalence and incidence of blood borne viral infections. Among health care workers (HCWs) vaccination for hepatitis B is only offered to high-risk groups. The aims of this cross sectional survey were to determine the prevalence of hepatitis B, -C, and human immunodeficiency virus (HIV) among the staff at a Danish University hospital and to correlate this with risk factors for transmission. Additionally, we wanted to examine the current frequency of blood exposure, reporting habits and hepatitis B vaccination status in the staff. Of 1439 eligible hospital staffs included, 960 (67%) were HCWs. The overall human immunodeficiency virus (HIV)-, hepatitis C Virus (HCV)- and hepatitis B Virus (HBV)-prevalence was 0% (0/1439), 0.14% (2/1439) and 1.6% (23/1439), respectively. Twenty-three percent of HCWs were vaccinated against HBV. Age, blood transfusion and stay in endemic areas were associated independently to HBV infection as opposed to job-category, duration of employment, HBV vaccination status and blood exposure. Based on a 4-week recall period, the incidence of percutaneous blood exposure was 1.5/person-year. In conclusion the HIV and hepatitis prevalence was low despite frequent blood exposure and the principal risk factors were unrelated to work. Danish HCWs do not seem to be at increased risk of hepatitis B even though universal HBV vaccination has not been implemented.
To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).
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.
The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates =10mIU/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.
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.
ClinicalTrials.gov registration number NCT00652938.