Brief Reports
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 15, 2004; 10(2): 306-308
Published online Jan 15, 2004. doi: 10.3748/wjg.v10.i2.306
Can HB vaccine yield a booster effect on individuals with positive serum anti-HBs and anti-HBc markers ?
Ru-Xiang Wang, Ying Guo, Chang-Hong Yang, Yu Song, Juan Chen, Fu-Sheng Pang, Shao-Ping Lei, Xiao-Ming Jia, Jin-Ying Wen, Christina Y. Shi
Ru-Xiang Wang, Ying Guo, Yu Song, Juan Chen, Shenyang Center for Disease Control and Prevention, Shenyang 110031, Liaoning Province, China
Chang-Hong Yang, Dongling District Anti-epidemic Station, Dongling District, Shenyang 110015, Liaoning Province, China
Fu-Sheng Pang, Shao-Ping Lei, Liaoning Center for Disease Control and Prevention, Shenyang, 110003, Liaoning Province, China
Xiao-Ming Jia, No.2 Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Jin-Ying Wen, Shenyang 606 Hospital, Shenyang110015, Liaoning Province, China
Christina Y. Shi, Vita-Tech Canada, 1345 Denison Street, Markham, Ontario, Canada L3R 5V2
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Ru-Xiang Wang, Shenyang Center for Disease Control and Prevention, 37 Qishanzhong Road, Huanggu District, Shenyang 110031, China. rxwtxh@pub.sy.ln.cn
Telephone: +86-24-86853243 Fax: +86-24-86863778
Received: April 12, 2003
Revised: October 4, 2003
Accepted: October 11, 2003
Published online: January 15, 2004

Abstract

AIM: To evaluate if HB vaccination can yield a booster effect on the anti-HBs level of those naturally acquired HBV positive markers.

METHODS: Sera were collected from 1399 newly enrolled university students aged between 18-20 years at the entrance medical examination in 2001. Forty-four students (28 males and 16 females) with positive serum anti-HBs and anti-HBc markers served as an observation group and another 44 students (24 males and 20 females) without any HBV markers as the control. HB vaccination was given to all the students without positive serum HBsAg according to 0, 1, 6 month regimen and the peripheral venous blood was sampled from those of both observation and control groups for anti-HBs detection one month after the second and third doses. Anti-HBs levels were measured by ELISA.

RESULTS: The seroconversion rate of anti-HBs in the control group was 100% after the second dose, but the geometric mean titers (GMTs) were low. The tendency of serum anti-HBs changes after the 3rd dose was completely different between the two groups. Although more than half of those with positive anti-HBs and anti-HBc showed a mild increase of anti-HBs levels after the 2nd boosting dose (mean anti-HBs level was 320:198 mIU), but the increase of serum anti-HBs titer was much smaller than that in the control group. The averages of their initial serum anti-HBs levels and the levels after the 2nd and 3rd doses were 198, 320 and 275 mIU respectively. All the subjects from the control group had an obvious increase in their serum anti-HBs levels which was nearly 4 times the baseline level (302:78 mIU).

CONCLUSION: HB vaccination can not enhance anti-HBs levels in those with positive serum anti-HBs and anti-HBc markers.




INTRODUCTION

HB vaccination program has been well developed for neonates and younger adults in China. Nowadays, according to Chinese regulation all the newly enrolled university students are required to have their blood detected for HBsAg and those with negative HBsAg are eligible to receive HB vaccination. Since it has been well demonstrated that an additional dose can induce a booster effect on vaccinees’ serum anti-HBs titers, it is natural for most people to get the idea that the more doses they get, the more benefits they will gain. Our previous survey in a group of university students showed that HBsAg carrier rate in those of the 18-20 age group was about 4%-6% and when gained entrance to the university more than 50% students with positive serum anti-HBs or anti-HBc or both were vaccinated each year. Is it necessary to vaccinate the people with positive anti-HBc and anti-HBs markers To answer this question, we followed up the newly enrolled students from a university to observe the changes of their serum anti-HBs titers after HB vaccination, especially those with positive serum anti-HBs and anti-HBc markers before. The changes of serum anti-HBs titers in students without any HBV markers before the vaccination were observed after HB vaccination as the experimental control. The results might be helpful for the establishment of a scientific, reasonable and economic vaccination program against HBV infection in the adult population.

MATERIALS AND METHODS
Reagents

Ten µg of yeast recombinant HB vaccine (Lot No: 2990104-1) was produced in Kangtai Biological Pharmaceutical Company, China. ELISA kits of HBV markers were from Sino-American Biotechnology Company, Luoyang, China. ELISA kit of Measles antibody was provided by Institute of Virus, Chinese Center of Disease Control and Prevention, Beijing, China.

Subjects and vaccination methods

Forty-four students with positive serum anti-HBs and anti-HBc and 44 without any HB markers who experienced a regular medical examination in one college were selected to be investigated after vaccinated with HB vaccine according to 0, 1, 6 month scheme, in which the vaccine was intramuscularly injected into the deltoid muscle. All the subjects were also injected measles vaccine one week before the first dose of HB vaccination. An informed consent was given by each participant before the beginning of observation.

Determination of serum anti-HBs antibody

Serum anti-HBs antibody was measured respectively at one month after the 2nd and 3rd doses of HB vaccine. The sera were randomly chosen from 35 subjects with positive anti-HBs and anti-HBc to measure the antibodies (IgG) to both measles and HBsAg according to the manufacturer’s instructions. The resulting value was determined according to Holliger formula: mIU = 418×[EXP×0.9(S-N)/(P-N)-1] in the light of OD values. mIU of anti-HBs titers greater than 10 was considered as positive anti-HBs. t test was used to compare GMTs between groups and the difference was considered significant when P < 0.05.

RESULTS
Anti-HBs titers before and after HB vaccination in those with positive anti-HBs and anti-HBc

The tendency of serum anti-HBs changes after the 3rd dose was completely different between the two groups. Although more than half of those with positive anti-HBs and anti-HBc markers showed a mild increase of serum anti-HBs titer after the 2nd booster dose, the increase of serum anti-HBs titer (mean anti-HBs level was 198:320 mIU) was much smaller than that in the control group, in which 100% subjects had an obvious increase in their serum anti-HBs levels which was nearly 4 times their baseline (302:78 mIU).

It was interesting to note that the serum anti-HBs levels did not change in most of the subjects with positive anti-HBs and anti-HBc markers after the 3rd dose. The mean serum anti-HBs level of the baseline, after the 2nd and 3rd doses was 198, 320 and 275 mIU (Table 1) respectively.

Table 1 Comparison of booster effect on anti-HBs levels be-tween two groups.
Anti-HBs (anti-HBc pos.)
Anti-HBs (anti-HBc neg.)
No.BeforeAfter 2ndAfter 3rdNo.After 2ndAfter 3rd
dosedosedosedose
233381615783622240448471
233062662931631323625268
233104062952931324045598
233041684173372433248324
231164486762432763144
2314030374324311186314
2313937245634424105344656
231293094592251723913583
231051454514611723858253
231191622692521722683598
271385923875331721453384
271284064944492324063268
271303412721992320140370
2710318214814523141201340
27137533282112310826512
270013264242691712922970
271099912211617125178318
27133573373316171224522
271201514202071711878466
2222211543858817108236414
222254424173381710688350
2221428329346617102197264
2220617628220813139186291
222055472753771312917158
222011831931581312673264
241201285583931312593191
241072393562571311817176
24140354264091311453263
2414121227523113108216280
221383925346591310735338
2213066064350413102130252
1321424733124413101113216
1322349131517614130320520
232351062321991413165407
2413710847228014129320365
2220261205253183023063
182382443023031831073336
233224224635031611953395
182233333143891611230370
2512235531528616122200375
251392063613371610445420
251291163913031610830365
251213811920416107441476
182206550750616110107499
Total GMT198320275GMT78302
Effect of a boost dose on antibody titers of HBsAb and measles Ab

In order to confirm that all the subjects in this study had a normal immune competence, the serum antibodies to measles were detected in 35 subjects and an increased antibody level was observed in 91.4% (32/35) subjects after a booster dose. A comparison of antibody levels before and after a booster dose was made and the difference was statistically significant (P < 0.05, Table 2).

Table 2 Effect of a boost on antibody titers of HBsAb and measles Ab.
BoostA-HBsAb
B-HBsAb
C-HBsAb
MealsesAb
No.GMTNo.GMTNo.GMTNo.GMT
Before4419844198447835322
After443204427544302351 207
DISCUSSION

Hepatitis B vaccination has been implemented for 20 years, however, the disease remains a global problem[1-4]. Although the safety and efficacy of HB vaccine have been well demonstrated[5-16], few papers regarding the immune response of those with positive anti-HBs and anti-HBc to HB vaccination are available. In this study, we observed if a booster effect and a better protection against HBV infection could be obtained after HB vaccination in those with positive serum anti-HBs and anti-HBc markers.

It has been well demonstrated that the HB vaccine-induced antibody might gradually decline or was even undetectable some years after primary immunization[17-20]. It is not clear if such persons could be protected against HB infection following exposure to HBV[21]. Although some studies have proved that memory cells to HBsAg might exist in vaccinees for a long time even the serum anti-HBs was undetectable[19,22,23]. Whether additional booster doses should be used has been under discussion[17-20,23-25]. Considering the available data on measles vaccine, which showed that loss of detectable antibody following vaccination was correlated with the waning of immunity[26], a booster HB vaccination might be necessary.

Our data revealed that the serum anti-HBs levels in the subjects with positive serum anti-HBs and anti-HBc markers did not significantly increase one month after the 2nd dose of HB vaccination. Although a mild increase was seen in some cases, the elevation of serum anti-HBs levels in the observatory group was much less than that in the control in which 100% subjects had an obvious increase of serum anti-HBs levels that was nearly 4 times their baseline. After the 3rd dose, anti-HBs levels remained unchanged in most of the subjects with positive serum anti-HBs and anti-HBc markers compared with that in the control, in which a sharp increase of serum anti-HBs levels was observed after the 3rd dose. The phenomenon might be related to the following possibilities. First, the subjects with positive serum anti-HBs and anti-HBc markers before the vaccination might not be in a normal condition of immune competence during the observation period. In the present study, their increased response to measles after the booster dose was observed in 91.4% (32/35) subjects. Because measles vaccination has been well practiced in China and normally all the subjects have to be vaccinated in their early age, the increased immunological response could prove that the subjects had the normal immune competence. Second, the immune response to viruses can damage the host via the formation of immune complexes, or directly damage the infected cells. Thus, the poor response to the HB vaccine might probably relate to the damage caused by HBV before the vaccination.

HB vaccination program is implemented in children and adults in China. But the problem is that our current vaccination regimen is not completely suitable for adult vaccination. An appropriate vaccination program for the adult population has to be established to prevent the prevalence of HBV. Our results indicate that it is not necessary to vaccinate those with positive serum anti-HBs and anti-HBc because no significant increase of anti-HBs titers was observed after a standard HB vaccination. It suggests that the vaccine-induced anti-HBs can not be elevated in those infected with HBV naturally before the HB vaccination.

Footnotes

Edited by Wang XL

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