Persistence of anti-HBs 5 years after the introduction of routine infant and adolescent vaccination in Italy. Hepatitis B immune memory in children primed with hexavalent vaccines and given monovalent booster vaccines: an open-label, randomised, controlled, multicentre study. Long-term efficacy of recombinant hepatitis B vaccine and risk of natural infection in infants born to mothers with hepatitis B e antigen. Serologic response to oral polio vaccine and enhanced-potency inactivated polio vaccines. Twelve-year follow-up of a prospective randomized trial of hepatitis B recombinant DNA yeast vaccine versus plasma-derived vaccine without booster doses in children. Hepatitis B vaccination in high-risk infants: 10-year follow-up. Single dose inactivated hepatitis A vaccine: rationale and clinical assessment of the safety and immunogenicity. Early immunisation with hepatitis B vaccine: a five-year study. Prevalence of anti-hepatitis B and anti-hepatitis A antibodies among school aged children in Western Saudi Arabia. Assessment of hepatitis B vaccine-induced seroprotection among children 5-10 years old in Ulaanbaatar, Mongolia. A 7-year follow-up of newborns vaccinated against hepatitis B. Long-term protection of hepatitis B vaccine 18 years after vaccination.
A population survey was conducted to assess the duration of anti-HBs levels > 10 IU/l in vaccinees living in Lazio Region ( Italy ) 5 years after the introduction ( 15 June 1991 ) of compulsory vaccination of new-borns and 11-year-old children . A r and om sample of 1192 ( 533 children born in 1991 - -92 and 659 adolescents born in 1979 - -81 ) was selected . In 92.9 % of children and 94.1 % of adolescents anti-HBs titres were protective ( > or = 10 IU/l ) . These subjects with protective titres were divided into three categories : low responders ( anti-HBs titres = 10 - -500 IU/l ) , medium responders ( anti-HBs titres = 501 - -2000 IU/l ) and high responders ( anti-HBs titres > 2000 IU/l ) . Factors associated with the level of response were analysed , using a multiple politomic logistic regression analysis . Greater age at first dose ( 11 - -12 years ) was associated with higher titres ( OR = 2.1 , 95 % CI = 1.4 - -3.2 for medium responders and OR = 3.0 , 95 % CI = 1.9 - -4.8 for high responders ) . Simultaneous administration of DT vaccine was associated with lower titres ( OR = 0.4 , 95 % CI = 0.2 - 0.8 for medium responders and OR = 0.3 , 95 % CI = 0.1 - -0.7 for high responders ) BACKGROUND In 2000 , hexavac and infanrix hexa were licensed in Europe for primary immunisation of children against diphtheria , tetanus , pertussis , poliomyelitis , hepatitis B , and invasive infections caused by Haemophilus influenzae b. In 2005 , hexavac was suspended because of concerns about the long-term immunogenicity of its hepatitis B component . We aim ed to assess the duration of immunity and need for booster injections in children primed with these vaccines . METHODS In an open-label , r and omised , controlled , multicentre study in six local health units and at the Bambino Gesù Paediatric Research Hospital in Italy , antibody concentrations were measured 5 years after immunisation of infants with hexavac or infanrix hexa . Children with concentrations of antibodies to hepatitis B surface antigen ( anti-HBs ) lower than 10 mIU/mL were r and omly assigned by simple r and omisation to receive a booster of HBVaxPro or engerix B monovalent hepatitis B vaccine and tested 2 weeks later . Primary endpoints were the proportion of children with anti-HBs concentrations of at least 10 mIU/mL , geometric mean concentrations ( GMCs ) of antibody 5 years after vaccination , and the proportion of children with anti-HBs concentrations lower than 10 mIU/mL who had anamnestic response to booster . The study is registered with Agenzia Italiana del Farmaco , code FARM67NFPN . FINDINGS 1543 children were enrolled , 833 had received hexavac and 710 infanrix hexa . 831 children who received hexavac and 709 who received infanrix hexa  were included in the analysis . 319 children who received hexavac ( 38.4 % , 95 % CI 35.1 - 41.7 ) had anti-HBs concentrations of at least 10 mIU/mL compared with 590 who received infanrix hexa ( 83.2 % , 80.5 - 86.0 ; p<0.0001 ) . GMCs before booster were 4.5 mIU/mL in the hexavac group compared with 61.3 mIU/mL in the infanrix hexa group ( p<0.0001 ) . After booster 409 ( 92.1 % , 89.6 - 94.6 ) of 444 children primed with hexavac and 99 ( 94.3 % , 89.8 - 98.7 ) of 105 primed with infanrix hexa had anti-HBs concentrations of at least 10 mIU/mL ( p=0.4 ) ; GMCs were 448.7 mIU/mL and 484.9 mIU/mL ( p=0·6 ) . The two booster vaccine groups did not differ in number of side-effects ; no serious adverse events were reported . INTERPRETATION 5 years after immunisation with hexavalent vaccines , immunological memory seems to persist in children with anti-HBs concentrations lower than 10 mIU/mL , suggesting that booster doses are not needed . Additional follow-up is needed . FUNDING Agenzia Italiana del Farmaco To evaluate the long-term protection afforded by the vaccine , recombinant hepatitis B ( HB ) vaccine was given to 171 infants born to hepatitis B e antigen-positive carrier mothers . Group A ( 53 infants ) and group B ( 57 infants ) received four doses of HB vaccine at birth and at 1 , 2 , and 12 months of age , with a dose of 20 micrograms in group A and 10 micrograms in group B. Group C ( 61 infants ) received three 20 micrograms doses of HB vaccine at birth and at 1 and 6 months of age . These children were followed up annually up to 5 years of age . Six children ( 4 % ) became HB carriers before 1 year of age , and the carrier state persisted to the end of follow-up . The overall seropositive rate of HB surface antibody ( anti-HBs ) dropped from 99 % at 1 year of age to 83 % at 5 years of age . Among 548 serum pairs taken at 1-year intervals from children negative for HB surface antigen ( HBsAg ) , a fourfold rise of anti-HBs titer was noted in 58 ( 11 % ) and a 10-fold rise of anti-HBs was noted in 17 ( 3 % ) . Maternal HB core antibody disappeared in most children ( 151/152 , 99 % ) before 2 years of age . Natural infections , as judged by persistence or reappearance of HB core antibody , occurred in 19 of 163 ( 12 % ) HBsAg-negative children . None of these episodes was associated with HBsAg positivity . We conclude that the long-term protection afforded by recombinant HB vaccine is satisfactory and that a further booster dose before 5 years of age is not necessary In a r and omized , controlled trial carried out from November 1980 to July 1983 involving 1,114 infants in Baltimore City and in Baltimore and Prince George 's counties , Maryl and , the serologic response to three doses of two enhanced-potency inactivated polio vaccines was compared with the response to three doses of oral polio vaccine .  The mean ages at vaccination were 2.2 , 4.7 , and 19.9 months , respectively , for the three doses .  Seroconversion after the first dose varied from 35 % to 84 % , and it was higher after oral polio vaccine than after either of the enhanced-potency inactivated polio vaccines for polioviruses types 2 and 3 . Approximately two and one-half and 16 months after the second dose , almost all inactivated polio vaccine recipients had antibodies against all three virus types ( 98 - 100 % ) . Fewer oral polio vaccine recipients had detectable antibodies to type 1 ( 89 - 92 % ) and to type 3 ( 96 % ) . After three doses of vaccine , all children had antibodies against types 2 and 3 . Approximately 1 % of the inactivated polio vaccine recipients and 3 % of the oral polio vaccine recipients lacked antibody to type 1 . One or two doses of oral polio vaccine stimulated higher reciprocal geometric mean antibody titers against type 2 poliovirus than did the inactivated polio vaccine . For the other two types , the results were mixed . The third dose of inactivated polio vaccine produced significant increases in the reciprocal geometric mean titers against each of the three poliovirus types and result ed in significantly higher reciprocal geometric mean titers after three doses of vaccine for recipients of inactivated polio vaccine than for recipients of oral polio vaccine A total of 318 children were prospect ively r and omized in group 1 with two 5-microg doses of recombinant vaccine given at 0 and 1 month ; in group 2 with three 5-microg doses of recombinant vaccine given at 0 , 1 , and 6 months ; or in group 3 with three doses of plasma-derived vaccine given at 0 , 1 , and 6 months . Eleven subjects with a hepatitis B surface antigen antibody ( anti-HBs ) titer of less than 10 mIU/mL at 12 months were given an extra dose of  vaccine and were excluded from analysis . No booster doses were given to any other subjects . All children were followed up yearly for the level of anti-HBs titers and for the detection of hepatitis B infection . At the 12th year of follow-up , there were significantly fewer subjects with anti-HBs of 10 mIU/mL or above in group 1 ( 60.4 % ) when compared with group 2 ( 81.4 % ; P = .0287 ) and group 3 ( 79.0 % ; P = . 0381 ) . The geometric mean titers ( GMTs ) of subjects of group 1 were significantly lower than those of group 2 and group 3 throughout the 12 years of follow-up . A total of 65 subjects had one or more episodes of anamnestic response . No subject became positive for hepatitis B surface antigen ( HBsAg ) ; 2 became positive for hepatitis B core antigen antibody ( anti-HBc ) . In conclusion , the long-term protective immunity was better with three doses of hepatitis B vaccine ( either the recombinant or plasma-derived ) than with two doses . However , protection from hepatitis B infection could be equally achieved by either two doses or three doses of the vaccine . Booster doses were not necessary , probably because of effective anamnestic response The long-term efficacy of  hepatitis B vaccination among high-risk infants was determined in 805 vaccine responders , immunized at birth in Taiwan during 1981 - 1984 and followed to age 10 years , via life table survival and Cox multivariate analyses . At 10 years , cumulative persistence of antibody to hepatitis B surface antigen ( anti-HBs ) was 85 % , and cumulative incidence of hepatitis B virus ( HBV ) infection was 15 % . Three children became carriers . Twelve-month anti-HBs titer was the strongest predictor of efficacy . The higher the initial titer , the lower the risk of anti-HBs loss ( relative risk [ RR ] , 0.26 for titer of 100 - 999 mIU/mL ; RR , 0.08 for titer > 1000 mIU/mL ; P<.001 ) and HBV infection ( RR , 0.55 and 0.27 ; P<.05 ) . Maternal hepatitis B e antigen positivity but not hepatitis B immunoglobulin dose or gender predicted greater antibody persistence to age 10 years . Because the level of antibody persistence remained high and few became carriers , booster revaccination within 10 years seems unnecessary In comparison with the classical immunisation schedules ( 0 - 1 - 6 or 0 - 1 - 12 months ) for hepatitis A , a 0- and 12- or a 0- and 6-month schedule would have important advantages by reducing the number of injections and discomfort and increasing scheduling convenience and patient compliance . It would be convenient if a single dose with enough antigen could protect both rapidly and for at least 12 months , when the booster dose would be given . Several clinical trials have been carried out with an inactivated hepatitis A vaccine containing 1,440 EL.U. ( 1 ml ) , according to a 0 - 12 and a 0 - 6 vaccination schedule . This hepatitis A vaccine is safe and well tolerated . It offers a rapid seroresponse : 14 days after a single dose the seroconversion is 88 % ( 95 % C.I. : 84.6 - 90.9 ) . The 0 - 12 schedule study showed good persistence of hepatitis A virus ( HAV ) antibodies with a seroconversion rate of almost 95 % at month 12 . Booster doses given at 6 or 12 months result in a substantial rise in antibody levels ; according to these antibody titres , the 1,440 EL.U. vaccine can be expected to confer comparable duration of protection as the 720 EL.U. vaccine , i.e. , 10 - 20 years . Preliminary data show that timing of the booster may not be critical for the antibody response . In conclusion , the 1,440 EL.U. hepatitis A vaccine is safe , offers rapid seroconversion , and is highly immunogenic . The persistence of HAV antibodies until month 12 allows a certain flexibility in the administration of the booster : month 6 or 12 , and a 0 - 12 or 0 - 6 schedule can increase the vaccination compliance We evaluated the response to the recombinant Hepatitis B vaccine using an accelerated schedule versus the traditional schedule by study ing the immunologic memory induced in 200 children with HBs-Ag negative mothers . At seroconversion , the traditional schedule presented a higher percentage of children with serum HBs-Ag concentrations over 100 mIU/ml than the accelerated schedule . After five years this difference was no longer statistically significant and children who presented anti-HBsAg concentrations below 10 mUI/ml  received an additional booster dose which stimulated the antibody concentration to exceed 100 mIU/ml in all cases . Recombinant HBV vaccine induced better long term immunologic memory when it was administered earlier OBJECTIVE To determine the seroprevalence of antibodies to hepatitis B virus ( HBV ) and hepatitis A virus ( HAV ) among children in Jeddah , Kingdom of Saudi Arabia ( KSA ) and to evaluate the need of anti-HAV mass vaccination . METHODS This study was carried out on r and om sample s of schools located at different regions in Jeddah , KSA during the year 2004 . A total of 527 sera , ( 285 males and 242 females ) , collected from children aged ( 4 - 14 years ) were tested for anti-hepatitis B surface ( antigen ) ( HBsAb ) and anti-HAV viruses antibodies by enzyme linked immunosorbent assay technique . RESULTS Approximately 98 % of children received HBV while 49 % of received HAV vaccine . For HBV the overall seropositivity was 75 % while HAV was 28.7 % , whereas seronegativity was 14 % for HBV and 70.5 % for HAV . Percentage of seropositivity against HBV was elevated in vaccinated versus non-vaccinated children ( p < 0.000 ) . In vaccinated children against HBV , percentage of seropositivity was elevated in children attending public versus those attending private and no schools ( p < 0.000 ) and in Saudi versus non-Saudi children ( p < 0.05 ) . In vaccinated and non-vaccinated children against HAV , percentage of seropositivity was elevated in children attending public versus those attending private schools ( p < 0.000 ) and no schools ( p < 0.000 ) and in males ( p < 0.05 ) versus females ( p < 0.01 ) . In vaccinated children , percentage of seropositivity for HBV obtained by age range from 4 - 6 years was 78.7 % , for 7 - 11 years 74.4 % and for 12 - 14 years 72.6 % , whereas for HAV virus , seropositivity was 14.8 % for 4 - 6 years , 38.3 % for 7 - 11 years and 28.6 % for 12 - 14 years . CONCLUSION Despite successful coverage of mass vaccination against HBV among school aged children , in Jeddah , KSA , there are high prevalence levels of seronegative with increasing age suggesting outbreak of disease among adolescent . Low prevalence of protective antibodies against HAV in vaccinated and non-vaccinated children may suggest application of mass vaccination program Hepatitis B virus infection is a serious public health problem . Mongolia is one of the countries with the highest rates of hepatitis B virus infection in the world . The routine immunization with the hepatitis B vaccine began nationwide in 1991 . The purpose of this study was to determine the persistence of seroprotection ( anti-HBs > or= 10 mlU/mL ) in children 5 - 10 years old that were immunized with the hepatitis B vaccine as infants . In total , 438 children were selected from six health facilities in Ulaanbaatar through a multistage r and om sampling method . Vaccination information was confirmed by checking the vaccination records kept in the health facilities . A blood sample was obtained from each child for anti-HBs , HBsAg and anti-HBc . Of 438 children , five ( 1.1 % ) were HBsAg positive and 58 ( 13.2 % ) were anti-HBc positive . Sixty infected children were excluded and a total of 378 ( 86.3 % ) sera were evaluated . The seroprotective antibodies were detected in only one-fourth of the children at the age of ten . Titres of anti-HBs decreased significantly with age ( Linear regression p = 0.01 ) . This decrease is primarily due to the rapid decrease in children living in ger areas ( p < 0.001 ) compared to children living in apartment areas ( p = 0.152 ) . On the other h and , children living with higher socio-economic status had more exposure to blood-borne pathogens , probably due to inappropriate health-seeking behaviors Of 79 children born to asymptomatic HBsAg chronic carrier mothers and vaccinated at birth against hepatitis B , a total of 71 , 66 and 56 could be serologically assessed after 1 , 5 and 7 years , respectively . Anti-HBs titres ( geometric means ) of responders decreased from 2475 to 143 IU l-1 between 1 and 5 years of age and dropped to 82 IU l-1 by 7 years . At this time , a booster dose given to 34 children who showed anti-HBs titres lower or slightly higher than 100 IU l-1 significantly increased titres from 34 to 2985 IU l-1 ( p < 0.001 ) . Children whose titres following perinatal vaccination reached 100 to 1000 IU l-1 or above 1000 IU l-1 maintained protective levels ( > 10 IU l-1 ) for 3 and 5 years , respectively . As in adults , anti-HBs titres recorded after the initial vaccination indicate the time at which infants should receive booster vaccination INTRODUCTION This is the third evaluation study of the hepatitis B virus ( HBV ) vaccination program , initiated in 1989 in Saudi Arabia . AIMS This study sought to assess the efficacy and long-term protection of the hepatitis B vaccine among Saudi adolescents . METHODS School students between the ages of 16 and 18 years were r and omly chosen from high endemic ( Aseer ) , intermediate endemic ( Madinah ) , and low endemic ( Al-Qaseem ) areas of the country .  Hepatitis B surface antigen ( HBsAg ) , hepatitis B core IgG antibody ( anti-HBc ) , and hepatitis B surface antibody ( anti-HBs ) were measured using st and ard techniques . RESULTS A total of 1355 students ( 689 males and 666 females ) were selected r and omly from the three areas . No cases of positive HBsAg or anti-HBc were detected among the study population . Five hundred and ten students ( 38 % ) showed protective anti-HBs titers ( > /= 10mIU/ml ) , while 528 ( 39 % ) students had undetectable anti-HBs titers ( < 1 mIU/ml ) . CONCLUSIONS This study shows the excellent efficacy of the HBV vaccination program in Saudi Arabia 18 years after its launch . Based on this study and others , a booster dose for the adult population appears to be unnecessary
BACKGROUND The duration of protection after  hepatitis B vaccination in early infancy is unclear and may be related to vaccination schedule , dosage , vaccine type and population characteristics .
Factors potentially influencing waning immunity were assessed .