| [Background]Viral Hepatitis B is one of the major public health problems that endanger the health of the global population,Hepatitis B Virus(HBV)can induce acute and chronic hepatitis and ultimately transformed into liver failure,liver cirrhosis and liver cancer,seriously endangering the population health and life,for the social and economic development has a great impact.China had a large number of people suffering from hepatitis B,the latest national blood serum epidemiology survey in 2014 shows that 1 to 4 years old and 1 to 29 years old people hepatitis B surface antigen(HBsAg)positive rate has been reduced to 0.32%and 2.64%,respectively,while the adult HBsAg positive rate is still at a high level.Hepatitis B vaccine(HepB)vaccination is the most effective measure to prevent and control HBV infection,and its effect has been verified in our country and many other countries and regions.China's implementation of newborns vaccination of hepatitis B vaccine strategy has been more than 20 years,children's HBV infection has been effectively controlled,and uninfected adults have become the main susceptible population.At present,China has only individual pilot areas to carry out adult HepB free vaccination,the rest of areas are still in accordance with the principle of voluntary,at their own expense,this imperfect vaccination strategy led to adult HepB vaccination rate at a low level.Therefore,improving the vaccination rate of HepB in adult population,adjusting and improving the immunization strategy of HepB in adult population has become the urgent task of accelerating the control of hepatitis B in China.The persistence of antibody is an important indicator to determine the effect of vaccine.The positive rate of antibody to hepatitis B virus surface antigen(anti-HBs)and geometric mean concentration(GMC)gradually decreased with age,and the rate of decline decreased with the time of vaccination,so it be an important issue focused by researchers that whether it is needed to carry out hepatitis B reinforce immunization and when to carry out.At present,antibody persistence in the adult after primary vaccination observation is relatively less,andthe results of domestic reports are quite different.Following up immunization persistence obersvation in the adult has great significance for making and adjusting adult hepatitis B immunization strategy.[Objectives]1.To explore the effects of humoral immunity and immune recall reaction persistence with time in 12 years after HepB primary vaccination among the adults by different immunization schedules.2.To analyze influencing factors of humoral immune persistence after HepB primary vaccination in the adults.3.To explore breakthrough infection rates in adults after HepB primary vaccination.Based on the above research results,to provide suggestions about adults' hepatitis B reinforce immunization strategy in China.[Methods]The initial source of this study was the cohort of HepB immunization observational study established in 2003 and belong to the follow-up observation of humoral immune persistence after primary immunization for 12 years.In 2003,three villages were randomly sampled in a Town,Jiyang County,Shandong Province.All 15?40 years old healthy residents of the villages were collected blood samples on the basis of informed voluntary.Hepatitis B surface antigen(HBsAg),anti-HBs and antibody against hepatitis B core antigen(anti-HBc)were detected by Solid Phase Radioimmunoassay(SPRIA);the HBV susceptible population(referring to HBsAg,anti-HBs and anti-HBc three indicators all negative)that no immue history of HepB were randomly divided into two groups for hepatitis B vaccination.Two groups were inoculated with 101?g/dose of recombinant hepatitis B vaccine(yeast)(manufactured by Shenzhen,Guangdong Kangtai Biological Products Co.,Ltd.)on 0-1-6 schedule and 0-6 schedule,and blood samples were collected 1 month after the last vaccination,while quantitative detection of anti-HBs(SPRIA method).In the above study,3 doses of HepB were vaccinated and blood samples collected 1 month after the last vaccination were the subjects of this study.In April 2015,the 5ml venous blood sample were collected from each participant,the isolated sera were frozen and stored in Shandong Province CDC and were detected for quantitative anti-HBc and anti-HBs by chemiluminescence microparticle immunoassay(CMIA)(Abbott reagent,Abbott ARCHITECT-i2000 Immuno-luminescence detector,the same below).Those whose anti-HBs titers were low than protective level(anti-HBs<10 mIU/ml)were given a challenge dose of hepatitis B vaccine and titers of anti-HBs were detected 14 days after the challenge.Through above analysis of the follow up results,the immune persistence and influencing factors after vaccinate HepB by different immunization schedules were comprehensive evaluated.When HepB was first vaccinated,all subjects were questionnered,including age,gender,height,weight,history of HepB vaccination and HBV infection,history of smoking and alcohol consumption.During the 12 years(2015)follow-up,all subjects who completed 3 doses of HepB and agreed to participate in the follow-up survey were asked and filled in the case questionnaire.At the same time,the subjects whose anti-HBs at follow-up were<10mIU/ml and received an additional 1 dose of HepB(challenge dose)were also investigated.All of the above questionnaires were conducted by the local Center for Disease Control and Prevention(CDC)professionals who had been trained by face-to-face manner to investigate all the vaccinated subjects.The researcher is responsible for compiling the unified EPI Data 3.1 database for data double entry,using IBM SPSS Statistics 24.0(online version)and STATA 11.2 softwares for data statistical analysis.?2 test was used to compare ratios in different groups;normal measurement material t test or single factor ANOVA were used to compare GMC in different groups.Researchers regarded age,gender,schedule of vaccines in primary immunization,GMC level and other factors as dependent variables separately and used multi-factor logistic regression model as well as multi-factor linear regression model to analyze influencing factors of anti-HBs positive rate,GMC as follow-up and postchallenge anti-HBs positive rate.[Results]1.Anti-HBs positive rate in following up:A total of 396 participants were followed up and anti-HBs?10mIU/ml were found of 249(62.88%,249/396).This positive rate in 12 years after primary vaccination declined by 28.53%compared with that in 1 month after primary vaccination.For two immunization schedules,anti-HBs positive rate in following up were 71.78%(145/202)and 53.61%(104/194)by turns of 0-1-6 schedule and 0-6 schedule.The positive rate of anti-HBs in different immunization schedule was statistically significant(?2=14.44,P<0.001).2.Anti-HBs GMC in following up:Anti-HBs GMC as follow up was 19.85(95%CI:16.28?24.20)mIU/ml,0-1-6 schedule and 0-6 schedule anti-HBs GMC were 31.05(95%CI:23.75?40.61)mIU/ml and 12.48(95%C7:9.43?16.52)mIU/ml,respectively,the differences in two schedules were statistically significant(t=4.63,P<0.001).3.Factors influencing anti-HBs positive rate and GMC in following up:After 12 years of follow up,the anti-HBs positive rate and GMC increased with the increase of the anti-HBs level after primary vaccination,the difference was statistically significant(P were less than 0.001).Multivariable analysis showed that the anti-HBs positive rate and GMC at follow-up are unrelated to age when primary vaccination,gender,BMI,history of tobacco and alcohol,family history of hepatitis B and chronic(P>0.050),but it was related to the immunization schedule and anti-HBs titer after primary immunization(P were less than 0.050).4.Breakthrough infection rate in following up:In all 396 individuals,there are 20 breakthrough infection cases and breakthrough infection rate was 5.05%(20/396).This rate in 0-1-6 schedule and 0-6 schedule was 4.95%(10/202)and 5.15%(10/194),respectively,with no statistical significance(?2=0.007,P=0.940).The breakthrough infection rate with subjects at follow up whose family memebers suffering from hepatitis B(28.57%)was higher than that subjects whose family memebers without hepatitis B(4.62%),the difference was statistically significant(P<0.050).5.The observation of humoral immune recall reaction:A total of 396 participants were followed up and anti-HBs<10mIU/ml was found in 148(37.28%,148/397).The challenge dose vaccination and postchallenge antibody detection were completed for 93 participants(62.84%,93/148)and 92(98.92%,92/93)showed immune memory response.The anti-HBs positive rate in 0-1-6 schedule and 0-6 schedule was 97.67%(42/43)and 100%(50/50),respectively,with no statistical significance(P=0.462);anti-HBs GMC after challenge dose was 3045.68mIU/ml(95%CI:2197.52?4221.19)mIU/ml,which was similar between 0-1-6 schedule[3527.48(2145.15?5800.58)mIU/ml]and 0-6 schedule[2684.30(1721.71?4185.08)mIU/ml](t=0.83,P=0.410).Multivariable analysis showed that BMI at primary vaccination and anti-HBs titer at follow-up were independently associated with postchallenge antibody titer(P=0.041 and 0.016,respectively).[Conclusions]1.Antibody positive rate in 12 years after primary vaccination by different schedules was still at a high level(53%?71%),however,the decrease of GMC from 183.25(150.79?222.69)mlU/ml to 19.85(16.28?24.20)mIU/ml,which the rate of decline was close to 90%.The sharp decrease of GMC will increase the risk of breakthrough infection.2.The results of 12 years follow up showed that the antibody positive rate and GMC in the 0-1-6 immunization schedule was significantly higher than that of the 0-6 immunization schedule,and the immune persistence effect was better.3.The higher antibody levelafter primary vaccination,the higher positive rate of follow-up antibody andthe better antibody persistence after 12 years.4.In the vaccinated challenge dose population,the higher the antibody level at follow up,the stronger the immune recall reaction.5.The humoral immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults,besides specific HBV exposure and booster doses were not needed.[Suggestions]1.Adults may have good humoral immune persistence after primary hepatitis B vaccination,but people who are in high risk of specific exposure,such as family members with HBV infection,intravenous drug users and medical personnel who contact blood products frequently,the anti-HBs level should be checked regularly.When the titer of anti-HBs is less than 100 mIU/ml,we should strengthen the immunity to prevent the occurrence of breakthrough infection.2.At the follow-up,it was found that the positive rate of anti-HBs and GMC in 0-1-6 immunization schedule were higher than those of 0-6 immunization schedule,and the immune persistence was better.However,because of the high mobility,poor compliance and other reasons,the whole process of the three doses vaccination rate was low.The simplified 0-6 immune schedule can improve the vaccination rate,and 53%of the populations still reach the level of antibody protection after 12 years.lt is suggested that the 0-1-6 immunization schedule should be adopted as a priority for adults,but the simplified 0-6 immunization schedule can be used for those with high mobility and poor compliance.3.In primary vaccination population,normal weighted and low weighted vaccinees immune recall reaction were stronger than over weighted vaccines.It is suggested that adults should control body weight,arrange diet reasonably and exercise proper amount of physical exercise to improve their immune response ability.4.Because of the large number of adult population and high mobility in China,and the regional immune service resources are not balanced and other reasons,to complete 3 doses of HepB vaccinated in adults is more difficult,it is recommended for different characteristics of the individual to take precise vaccination program. |
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