Evaluation Of The Efficacy Of Live Attenuated And Inactivated Hepatitis A Vaccine

[Purpose]Viral hepatitis type A or hepatitis A is an acute intestinal infectious diseases caused by Hepatitis A virus(HAV).It is known as the one of the most important public health problems in developing countries.With the advance of social economy as well as the improvement of sanitary conditions,the morbidity of hepatitis A has dropped significantly.But there are still 1.5 million cases of hepatitis A being reported each year worldwide.WHO(World Health Organization)has suggested in its Proposals about Viral Hepatitis Type A Vaccine that middle income countries should carry out large-scale inoculation of hepatitis A vaccine.Back in 2007,China has included hepatitis A vaccine in National Immunization Program for Children(NIP).Meanwhile the medical biology research institute of CAMS has produced Weisairuiji,the freeze-dried live attenuated hepatitis A vaccine as well as Weisairuian,the inactivated hepatitis A vaccine.Both these vaccines have been developed and produced independently by China with proprietary intellectual property rights.As an innovative vaccine,it can function as a preventative method for such serious infectious disease as hepatitis A,featuring wide application in NIP.Based on previous research,this IV clinical trial aims to monitor the effectiveness,safety and quality of above two vaccines by carrying out large-scale clinical researches in multiple provinces,multiple centers in mass subject amount and special population groups on hepatitis A attenuated live vaccine and inactivated hepatitis A vaccine IV stage.This article has chosen the titer quantitative detection of anti-HAV serum sample from different time points in Xiangshui County,Jiangsu Province.According to statistical analysis of SR and GMT,the comprehensive evaluation of immunogenicity and immunological persistence of those two vaccines has been drawn.To make sure the results is stable and reliable,lab has verified the test method accuracy,reagent precision and report scope design of linear estimation.In the light of medical lab-quality and capability requirement from ISO 15189(International Standardization Organization 15189),namely lab should design and bring to practice the plan adjusted by measuring system and authentic verification,EP documents have also been used as a reference.[Method]In line with the random,double-blinded and parallel comparison design,children and adults who have not suffered popular hepatitis A or been inoculated with hepatitis A vaccine can be selected as subjects.The total number of vaccination for those two tests has reached 9,000.Among them,900 blood samples have been randomly extracted from each vaccine group with total blood sampling amount toping 1,800.With Roche Cobas e411 automatic electrochemical luminescent immune analyzer and auxiliary reagent,anti-HAV quantitative detection has been conducted.Referring to EP documents.verification for test methods,reagent precision,accuracy,report scope design(linear estimation)has also been made.Besides,researches statistically analyzed test results,calculated SR and GMT after inoculation.Through observing the protection effect and immunological persistence of above two vaccines,further comparison has been conducted.[Result]The verification result for test methods,reagent precision,accuracy,report scope design(linear estimation)indicated that both the batch mean value and total mean value of low-value control A-HAV1 and high-value control A-HAV2 fell into the target value range of ± 3 SD,conforming to US CLIA ' 88 standard and further illustrating hepatitis A antibody test precision was acceptable.The bias of hepatitis A antibody test result accounted for 3.77%,lower than China industrial bias standard 4.3%,suggesting acceptable accuracy.Polynomial regression results showed that within the range of 3.66-83.17 IU/L(apparatus report range as 3.0-60.0 IU/L),fitting data points of cubic polynomial performed way better than linear ones.The gap value between linear fitting and cubic polynomial fitting was less than allowable deviation 4.02 IU/L,declaring that linear verification was acceptable.This test enabled stable and reliable hepatitis A antibody quantitative detection data for hepatitis A vaccine IV clinical trial on the basis of SR and GMT.In this case,both vaccines enjoyed impressive immunogenicity and immunological persistence.In terms of immunogenicity,after 28 days of the live attenuated HAV vaccine inoculation,GMT reached 979.67IU/L(95%CI:842.59-1139.04 IU/L)while SR achieved 98.11%(95%CI:95.65-99.38%).Meanwhile,28 days later following the first dose of inactivated hepatitis A vaccine,GMT topped 894.71IU/L(95%CI:793.08.56-1009.36 IU/L)while SR came to 99.64%(95%CI:98.01-99.99%).After the second dose,namely 28 days into the whole course,GMT attained 3697.67IU/L(95%CI:3373.31-4053.21 IU/L)while SR reached 100.00%(95%CI:99.10-100.00%).Results manifested that organism can been stimulated to generate higher titer anti-HAV and relevant protection,sharing same outstanding immunogenicity as other vaccines at home and abroad.According to consistent research results,anti-HAV titer of whole course was higher than only one dose which displayed that two-dose plan superior to one-dose when it came to inactivated hepatitis A vaccine.As for immunological persistence,during 3-year observation,the GMT and SRs of both vaccines have remained at quite high levels,an indication of great immunological persistence.With regard to live attenuated hepatitis A vaccine,after 1 year of inoculation,GMT and SR stood at 1538.08IU/L(95%CI:1300.71-1818.77 IU/L)and 99.63%(95%CI:97.97-99.99%)receptively.Two years later,GMT was 5472.88IU/L(95%CI:4638.01-6458.02 IU/L)while SR slightly declined to 97.07%(95%CI:94.31-98.73%).Three years later,GMT became 5252.33IU/L(95%CI:4478.40-6160.01IU/L)while SR picked up to 99.62%(95%CI:97.92-99.99%).For inactivated hepatitis A vaccine,one year after inoculation,GMT acted as 4311.00IU/L(95%CI:3635.52-5111.97 IU/L)while SR reached 100.00%(95%CI:98.82-100.00%);two years later,GMT featured 4283.25IU/L(95%CI:3725.27-4924.82 IU/L)and SR dropped to 96.73%(95%CI:94.07-98.42%);three years later,GMT was 7707.92IU/L(95%CI:6944.29-8555.52IU/L)while SR rose back to 00.00%(95%CI:98.75-100.00%).During observation,no GMT decline has been spotted for both vaccines.This made it even harder to reckon longest immune duration via statistic fitting.Meanwhile,both SRs faced a decrease in the second year and recovery in the third year.Besides,the gap between ups and downs for the live attenuated hepatitisA vaccine made no statistic sense.In comparison of immunogenicity and immunological persistence,it was found that with only one dose,there was no statistic difference of GMT 28 days later after inoculation.Nevertheless,comparing whole course of inactivated hepatitisA vaccine with live attenuated hepatitisA vaccine,it was noted that whether it was 28 days,1 year,2 years or 3 years after inoculation,the GMT of inactivated vaccine always boasted a higher level.As for statistic comparison of SR,the statistic meaning existed for difference between 28 days later after live attenuated hepatitis A vaccine inoculation and 28 days later after whole course inactivated hepatitisA vaccine inoculation.Apart from this,in other time points,there was no difference in vaccine SRs.[Conclusion]In a word,this essay has utilized Roche Cobas e411 automatic electrochemical luminescent immune analyzer and auxiliary reagent to verify the precision,accuracy and report scope(linear estimation)of Anti-HAV.After comparison of the inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine,results indicated that both vaccines enjoyed quite impressive immunogenicity and immunological persistence,suitable for further application and promotion.