[Abstract] With a view to evaluate the immunogenicity of different immunization schedules of the Healive inactivated hepatitis A vaccine in five mountain area villagcs, 167 children aged 5-11 years old. seronegative for hepatitis A virus were randomly divided into five groups. Four groups administered 250U/dose vaccine according to 0、1,0、3,0、6 and0、12 schedules respectively. The control group administered Havrix 720EIU inactivated hepatitis A vaccine. The results showed that the positive seroconversion rate were 97.0% and 95.5%, the geometric mean titers (GMTs) were 355mIU/ml and 251 mIU/ml, respectively by two and four weeks after the primary dose in trial groups. The seroconversion rate were all 100%, the GMT were 417mIU/ml, 391mIU/ml and 361mIU/ml by 3、6 and 12 montbs after the primary dose, respectively. Seroconversion rate were all 100% by the booster dose after one month in four groups, GMT were 14,893mIU/ml(0.12),>5,963mIU/ml(0、6)>3, 265mIU/ml(0、3), and 1,973mIU/ml(0、1),it had significant statistical difference. In control group, seroconveraion rare were 71.0% and 71% 4 weeks and 6 months after the primary dose respectively and were 100% by one month after the booster dose;GMT were 158mIU/ml、152mIU/ml and 1,104mIU/ml respective. The GMT protective level was over 12 time after receiving one dose of Healive inactivated Hepatitis A vaccine. 0、1immunlzation schedule can be used to accelerate the immunity. 0、3,0、6 and0、12 schedules can be fiexibaly applied according to requirements of diferent population. The 0、12 months is the best schedule.
[Author] Ren Yinhai, Chen Jiangting Wu wenting, et al
[key words] Inactivated hepatitis A vaccine; Immunogenicity; Immunization schedule
Healive Inactivated Hepatitis A (HA) Vaccine has been commercialized. Its children dose-type is 250U/dose and its 0-6month immune schedule is better than 0-3, 0-1month immune schedules and is our recommendation. In 2001-2002, we observed the immunogenicity of different immune schedules for (250U/dose) Healive Inactivated Hepatitis A Vaccine used by children in order to test the best schedule. Our report is as follows:
Materials and Methods
1. Vaccine Healive children-type dose inactivated hepatitis A vaccine produced by of Sinovac consists of viral antigen 250U/dose, which was compared with HavrixTM 720EIU inactivated hepatitis A vaccine produced by SmithKline Beecham.
2. Vaccinated object Healthy children were chosen from the villages with similar economic level, sanitary conditions and living habits in some mountainous area. These children were aged 5~10, who were segonegative for anti-hepatitis A viral antibodies (anti-HAV), had normal serum alanine aminotransferases (ALT) and had no anaphylactic experience before. They were divided into 4 groups randomly by unit of village, i.e., of 0-1, 0-3, 0-6 and 0-12 schedule groups.
3. Vaccination method and schedule It used the upper arm deltoid muscle injection. The 1st injection was the primary immunization and then the 2nd vaccine was injected respectively 1, 3, 6 and 12month afterwards through immunization, i.e., in 0-1, 0-3, 0-6 and 0-12 schedules.
4. Serology test Venous blood 3ml was sampled on an empty stomach each time, and blood serum was separated aseptically and stored for test under –20°C. The anti-HAV standard crystal for test, the freeze-dry crystal, was provided by WHO, which was dissolved in distilled water by 1amp./1.0ml, and the anti-HAV content 98.6IU/ml. They were bottled and stored under –20°C separately.
Anti-HAV seroconversion rate test used Abbott ELISA Anti-HAV reagent boxes with the batch No. 80450M200, and the sensibility was 22mIU/ml. The sample of competition restrain rate > 50% was decided as anti-HAV positive. Anti-HAV GMT test used the standard anti-HAV reagent produced by Tangshan Yian Biotech Co., Ltd. with the batch No. 021105 and the sensibility was 55mIU/ml. The relevant antibody GMT (mIU/ml) was calculated compared with the standard GMT OD value within the proper-dilute limit and different dilute samples.
5. Method of statistical analysis The SAS system process was used. The comparison of Anti-HAV seroconversion rates was tested by c2; anti-HAV GMT was shown by mIU/ml; the two-group comparison was tested by t.
Results
1. Domestic change of primary immunization of inactivated hepatitis A vaccine
By the 2nd week after the primary immunization of Healive inactivated hepatitis A vaccine, the anti-HAV seroconversion rate was 97.0%, and after 4 weeks, 3 months, 6 months and 12 months following the primary immunization, which gradually increased to 100%. GMT was 251mIU/ml~417 mIU/ml. For HavrixTM 720EIU inactivated hepatitis A vaccine, by the 4th week, the anti-HAV seroconversion rate was 71.0% which lasted 6 months, and GMT was mIU/ml~158 mIU/ml(See Table 1).
Table 1 Domestic Change following Primary Immunization of Inactivated Hepatitis A Vaccine
| Vaccine |
After-immunization period |
No. of people |
Anti-HAV seroconversion |
Antibody GMT (mIU/ml) |
| No. of people |
% |
| HealiveÒ |
2weeks |
33 |
32 |
97.0 |
355 |
| 4weeks |
67 |
64 |
95.5 |
251 |
| 3months |
34 |
34 |
100.0 |
417 |
| 6months |
33 |
33 |
100.0 |
391 |
| 12months |
36 |
36 |
100.0 |
361 |
| HavrixTM |
4weeks |
31 |
22 |
71.0 |
158 |
| 6months |
31 |
22 |
71.0 |
152 |
HealiveÒ seroconversion rates and GMTs compared with those of HavrixTM: c2(4weeks)= 9.717, P<0.05; t(4weeks) = 1.989, P<0.05; c2(6months)= 8.875, P<0.01; t(6months) = 2.006, P<0.01.
2. Comparison of different immune schedule inactivated hepatitis A vaccines
As to the four groups of 0-12, 0-6, 0-3, 0-1month immune schedules to vaccinate Healive inactivated hepatitis A vaccine, by the 1st month after the through immunization, their anti-HAV seroconversion rates were 100.0%l, and their GMTs were 14893mIU/ml, 5963mIU/ml, 3265mIU/ml and 1973mIU/ml respectively. 0-12month immune schedule anti-HAV GMT > 0-6month schedule’s > 0-3month schedule’s > 0-1month schedule’s, the difference has statistical significance. After 0-6 through immunization, HavrixTM 720EIU inactivated hepatitis A vaccine anti-HAV GMT was 1104mIU/ml(Sea Table 2).
Table 2 Anti-HAV Reactions after Through Immunication of Different Schedule HealiveÒ Inactivated Hepatitis A Vaccines
|
Immune schedule (month) |
No. of people |
Anti-HAV seroconversion |
Antibody GMT (mIU/ml) |
95% confidence interval |
| No. of people |
% |
| HealiveÒ |
0-1 |
33 |
33 |
100.0 |
1973 |
2757~1412 |
|
0-3 |
34 |
34 |
100.0 |
3265 |
4433~2403 |
|
0-6 |
33 |
33 |
100.0 |
5963 |
6300~5642 |
|
0-12 |
36 |
36 |
100.0 |
14893 |
18159~12209 |
| HavrixTM |
0-60 |
31 |
31 |
100.0 |
1104 |
1188~1025 |
t(0-12months,0-6months)=4.911,P<0.01;t(0-6months,0-3months)=1.997, P<0.01;
t(0-3months, 0-1month) = 1.997, P<0.05; HavrixTM(0-6months)= 2.000, P<0.01.
Discussion
By the 2nd week and the 4th week after the primary immunization of HealiveÒ inactivated hepatitis A vaccine, the anti-Hav seroconversion rates were 97.0% and 95.5% respectively; and by the 3rd month, 6th month and 12th month, which increased to 100%. The anti-HAV GMT was 251mIU/ml ~417mIU/ml, which changed little within 1 year. It showed that for children injecting one dose HealiveÒ inactivated hepatitis A vaccine, the antibody seroconversion rate was 100% and the GMT bottom value (251mIU/ml) was more than 12 times of the protective value limit, which greatly exceeded the GMT effective to prevent from infection. According to Van Herck K’s report, after immunization of inactivated hepatitis A vaccine, if GMT >200mIU/ml, the antibody could last more than 25 years. From observing 9-18 children susceptible to HAV infection, Lss SI stated that perhaps a single dose inactivated hepatitis A vaccine was applicable. Yong Poovorawan thought that an inactivated hepatitis A vaccine could weaken the cell adjustment immunization so it was unnecessary to boost immunization in order to obtain long-term protection. We thought that though the anti-HAV GMT of one injection immunization was lower than two-injection schedule’s, currently there was no evidence to show that the antibody lasted shorter. Therefore we should observe the long-term immunization effect of one-injection schedule and experimented the one-injection inactivated hepatitis A vaccine on village children in poor areas.
After the through immunization of 0-1month schedule, the anti-HAV seroconversion rate was 100.0%, and GMT was 1973mIU/ml, which was applicable to fasten immunization of tourists and working personnel in some hepatitis A epidemic area.
By the 1st month after the through immunization of 0-3, 0-6 and 0-12month schedules, the anti-HAV GMT were 3265mIU/ml, 5963mIU/ml, and 14893mIU/ml, therefore the 0-12month schedule GMT was much better than other schedule GMTs. Recent research has shown that longer injection interval of inactivated vaccines could produce better immunization feedback, especially for the vaccines containing adsorbent, vaccination interval longer than the prescription could not reduce the finally antibody titer. P Tandry and other researchers reinforced immunization for 124 people who had been vaccinated inactivated hepatitis A vaccines more than 24 months, even up to 66 months, after the primary immunization, who showed stronger immunization feedbacks. Therefore they concluded that HealiveÒ inactivated hepatitis A vaccine anti-HAV GMT was 0-12month schedule >0-6month schedule >0-3month schedule>0-1month schedule; HealiveÒ inactivated hepatitis A vaccine antibody seroconversion rate and GMT were averagely higher than those of HavrixTM. According to Chinese condition, one-injection immune schedule could be introduced in poor village areas; 0-1month schedule could be used to fasten immunization among special groups of people; and 0-3, 0-6 and 0-12month schedules could be applied according to different people’s needs. In a word, HealiveÒ inactivated hepatitis A vaccine convenient and flexible immune schedules provide wide applications for users of different purposes.
References:
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Original: Chinese J of Vaccines and Immunization August 2003, Vol.9 No.4
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