Edited by Wang XL
Published online Jan 15, 2004. doi: 10.3748/wjg.v10.i2.306
Revised: October 4, 2003
Accepted: October 11, 2003
Published online: January 15, 2004
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.
- Citation: Wang RX, Guo Y, Yang CH, Song Y, Chen J, Pang FS, Lei SP, Jia XM, Wen JY, Shi CY. Can HB vaccine yield a booster effect on individuals with positive serum anti-HBs and anti-HBc markers ? World J Gastroenterol 2004; 10(2): 306-308
- URL: https://www.wjgnet.com/1007-9327/full/v10/i2/306.htm
- DOI: https://dx.doi.org/10.3748/wjg.v10.i2.306
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.
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.
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.
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.
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.
|Anti-HBs (anti-HBc pos.)||Anti-HBs (anti-HBc neg.)|
|No.||Before||After 2nd||After 3rd||No.||After 2nd||After 3rd|
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).
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. 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, 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.
|1.||Cassidy WM. Adolescent hepatitis B vaccination. A review. Minerva Pediatr. 2001;53:559-566. [PubMed]|
|2.||Kralj N, Hofmann F, Michaelis M, Berthold H. [Current hepatitis B epidemiology in Germany]. Gesundheitswesen. 1998;60:450-455. [PubMed]|
|3.||Bayas JM, Bruguera M, Vilella A, Carbó JM, Vidal J, Navarro G, Nebot X, Prat A, Salleras L. [Prevalence of hepatitis B and hepatitis A virus infection among health sciences students in Catalonia, Spain]. Med Clin (Barc). 1996;107:281-284. [PubMed]|
|4.||Bonanni P. Universal hepatitis B immunization: infant, and infant plus adolescent immunization. Vaccine. 1998;16:S17-S22. [PubMed] [DOI]|
|5.||Kojouharova M, Teoharov P, Bahtchevanova T, Maeva I, Eginlian A, Deneva M. Safety and immunogenicity of a yeast-derived recombinant hepatitis B vaccine in Bulgarian newborns. Infection. 2001;29:342-344. [PubMed] [DOI]|
|6.||Liao SS, Li RC, Li H, Yang JY, Zeng XJ, Gong J, Wang SS, Li YP, Zhang KL. Long-term efficacy of plasma-derived hepatitis B vaccine among Chinese children: a 12-year follow-up study. World J Gastroenterol. 1999;5:165-166. [PubMed]|
|7.||Li H, Li RC, Liao SS, Yang JY, Zeng XJ, Wang SS. Persistence of hepatitis B vaccine immune protection and response to hepatitis B booster immunization. World J Gastroenterol. 1998;4:493-496. [PubMed]|
|8.||Rendi-Wagner P, Kundi M, Stemberger H, Wiedermann G, Holzmann H, Hofer M, Wiesinger K, Kollaritsch H. Antibody-response to three recombinant hepatitis B vaccines: comparative evaluation of multicenter travel-clinic based experience. Vaccine. 2001;19:2055-2060. [DOI]|
|9.||Ozaki T, Mochizuki H, Ichikawa Y, Fukuzawa Y, Yoshida S, Morimoto M. Persistence of hepatitis B surface antibody levels after vaccination with a recombinant hepatitis B vaccine: a 3-year follow-up study. J Oral Sci. 2000;42:147-150. [PubMed] [DOI]|
|10.||Jain A, Mathur US, Jandwani P, Gupta RK, Kumar V, Kar P. A multicentric evaluation of recombinant DNA hepatitis B vaccine of Cuban origin. Trop Gastroenterol. 2000;21:14-17. [PubMed]|
|11.||Al-Faleh FZ, Al-Jeffri M, Ramia S, Al-Rashed R, Arif M, Rezeig M, Al-Toraif I, Bakhsh M, Mishkkhas A, Makki O. Seroepidemiology of hepatitis B virus infection in Saudi children 8 years after a mass hepatitis B vaccination programme. J Infect. 1999;38:167-170. [PubMed] [DOI]|
|12.||Li H, Li RC, Liao SS, Gong J, Zeng XJ, Li YP. Long-term effectiveness of infancy low-dose hepatitis B vaccine immunization in Zhuang minority area in China. World J Gastroenterol. 1999;5:122-124. [PubMed]|
|13.||Liu HB, Meng ZD, Ma JC, Han CQ, Zhang YL, Xing ZC, Zhang YW, Liu YZ, Cao HL. A 12-year cohort study on the efficacy of plasma-derived hepatitis B vaccine in rural newborns. World J Gastroenterol. 2000;6:381-383. [PubMed]|
|14.||Li H, Wang L, Wang SS, Gong J, Zeng XJ, Li RC, Nong Y, Huang YK, Chen XR, Huang ZN. Research on optimal immunization strategies for hepatitis B in different endemic areas in China. World J Gastroenterol. 2000;6:392-394. [PubMed]|
|15.||Zeng XJ, Yang GH, Liao SS, Chen AP, Tan J, Huang ZJ, Li H. Survey of coverage, strategy and cost of hepatitis B vaccination in rural and urban areas of China. World J Gastroenterol. 1999;5:320-323. [PubMed]|
|16.||Shokri F, Jafarzadeh A. High seroprotection rate induced by low doses of a recombinant hepatitis B vaccine in healthy Iranian neonates. Vaccine. 2001;19:4544-4548. [PubMed] [DOI]|
|17.||Peces R, Laurés AS. Persistence of immunologic memory in long-term hemodialysis patients and healthcare workers given hepatitis B vaccine: role of a booster dose on antibody response. Nephron. 2001;89:172-176. [PubMed] [DOI]|
|18.||Li H, Li R, Liao S, Yang J, Zeng X. [Persistence of HB vaccine immune protection and response to hepatitis B booster immunization]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1998;20:54-59. [PubMed]|
|19.||Watson B, West DJ, Chilkatowsky A, Piercy S, Ioli VA. Persistence of immunologic memory for 13 years in recipients of a recombinant hepatitis B vaccine. Vaccine. 2001;19:3164-3168. [PubMed] [DOI]|
|20.||García Llop L, Asensi Alcoverro A, Coll Más P, Ramada Benedito MA, Grafiá Juan C. [Anti-HBs titers after a vaccination program in children and adolescents. Should a booster dose be given]. An Esp Pediatr. 2001;54:32-37. [PubMed]|
|21.||Wood RC, MacDonald KL, White KE, Hedberg CW, Hanson M, Osterholm MT. Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers. JAMA. 1993;270:2935-2939. [PubMed] [DOI]|
|22.||Wismans PJ, van Hattum J, De Gast GC, Endeman HJ, Poel J, Stolk B, Maikoe T, Mudde GC. The spot-ELISA: a sensitive in vitro method to study the immune response to hepatitis B surface antigen. Clin Exp Immunol. 1989;78:75-79. [PubMed]|
|23.||Trivello R, Chiaramonte M, Ngatchu T, Baldo V, Majori S, Moschen ME, Simoncello I, Renzulli G, Naccarato R. Persistence of anti-HBs antibodies in health care personnel vaccinated with plasma-derived hepatitis B vaccine and response to recombinant DNA HB booster vaccine. Vaccine. 1995;13:139-141. [PubMed] [DOI]|
|24.||Coursaget P, Yvonnet B, Chotard J, Sarr M, Vincelot P, N'doye R, Diop-Mar I, Chiron JP. Seven-year study of hepatitis B vaccine efficacy in infants from an endemic area (Senegal). Lancet. 1986;2:1143-1145. [PubMed] [DOI]|
|25.||Hadler SC, Francis DP, Maynard JE, Thompson SE, Judson FN, Echenberg DF, Ostrow DG, O'Malley PM, Penley KA, Altman NL. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med. 1986;315:209-214. [PubMed] [DOI]|
|26.||Measles prevention. MMWR Morb Mortal Wkly Rep. 1989;38 Suppl 9:1-18. [PubMed]|