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J Zhejiang Univ Sci B. Nov 2012; 13(11): 948–954.
PMCID: PMC3494034

Immunological effects of a 10-μg dose of domestic hepatitis B vaccine in adults*

Abstract

Objective: To evaluate the immunological effects of three types of domestic 10-μg/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to provide scientific evidence in support of adult hepatitis B vaccination. Methods: Adults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City, Shaoxing County and Tongxiang County, Zhejiang Province, China were selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc using a chemiluminescence immunoassay. Adults, aged 16 to 49 years and who were anti-HBs negative at baseline, received hepatitis B immunizations at 0, 1, and 6 months. Anti-HBs levels were assessed one month after the third and final vaccination. Results: A total of 1 872 adults were immunized and the average positive rate was 89.5%. Four types of hepatitis B vaccine were used, including three from Chinese companies (Shenzhen Kangtai, Dalian High-Tech, and North China Pharmaceutical) and one from a UK company (GlaxoSmithKline). Their seroconversion rates were 81.67%, 95.05%, 89.64%, and 86.81%, respectively. There was a significant difference between the anti-HBs positive conversion rates of the four types (P<0.005) but the seroconversion rates among the different vaccines were not significantly different (χ 2=2.123, P=0.145). The average anti-HBs geometric mean titers (GMTs) of non-immune adults immunized with each of the four vaccines were 177.28, 473.23, 246.13, and 332.20 mIU/ml, respectively. There were no statistically significant differences in the GMTs between the three types of domestic vaccine and the foreign vaccine (t=−1.575, P=0.116). Conclusions: Domestic recombinant hepatitis B vaccines can achieve immunization effects comparable to those of a foreign vaccine.

Keywords: Hepatitis B, Vaccines, Immunization, Geometric mean titer

1. Introduction

Hepatitis B virus (HBV) infection is a current global public health concern (Ganem and Prince, 2004). It is estimated that more than 2 billion people have been infected with HBV, including 360 million chronic carriers of the virus. HBV is responsible for about 600 000 to 1 200 000 deaths annually worldwide (WHO, 2000; Lavanchy, 2004; Goldstein et al., 2005; Ganczak et al., 2009). HBV infection is especially severe in China; according to a national seroepidemiological survey conducted in 2006, the rate of HBsAg carriers in the general population within the age range of 1 to 59 years is 7.18% (Liang et al., 2009a; 2009b). Thus, more than 93 million people are chronically infected with HBV in China (Lu and Zhuang, 2009). As there is currently no satisfactory treatment for chronic hepatitis B infection and related diseases, hepatitis B vaccination is regarded as the most economical and effective method to prevent and control hepatitis B infection (Chang et al., 2004; Ganem and Prince, 2004; Weinbaum et al., 2008; Shen and Yao, 2011).

Hepatitis B control has been administered through immunization planning management in China since 1992. There have been improvements in hepatitis B prevention and control in China within the past 20 years through mass vaccination with the hepatitis B vaccine. According to the 2006 survey, the HBV infection rate among Chinese children under the age of 15 has declined from 10% in 1992 to 2.08% today (Liang et al., 2009a; 2009b). With these advances in hepatitis B prevention and control, more attention is now being devoted to adult hepatitis B immunization in China. To protect the privacy of patients with hepatitis B, the Ministry of Public Health prohibits testing for HBV infection markers in medical examinations, so adult hepatitis B vaccine immunization is especially important. There is a lack of immunological performance data for hepatitis B vaccines in adults as adult hepatitis B vaccination has not been systematically carried out in many places. To assist the advancement of the hepatitis B control process and to further reduce the adverse effects of contracting HBV, we studied the effects of Chinese hepatitis B vaccines compared with a foreign vaccine in adults. Selected adults between the ages of 16 and 49 years were given a 10-μg dose of one hepatitis B vaccine at 0, 1, and 6 month intervals. The immune effects of different types of hepatitis B vaccines were then evaluated.

2. Materials and methods

2.1. Subjects

Subjects from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City and from Shaoxing County, Zhejiang Province, China were selected as experimental groups in this study. Subjects underwent serological screening and only those negative for HBsAg, anti-HBs, and anti-HBc could be deemed eligible and included in the study. About 700 subjects from each county were selected and each was given one vaccine. Subjects from Tongxiang County, as the compared group, were given the vaccine from GlaxoSmithKline, UK. All the counties had a similar economic status. The study was approved by the Institutional Ethics Committee of the Zhejiang Center for Disease Control and Prevention, China.

The inclusion criteria (Yao et al., 2011) included: (1) between the ages of 16 to 49 years and willing to participate in the study and provide informed consent; (2) willing to participate in the follow-up study and to provide blood samples after vaccination.

The exclusion criteria included: (1) reluctant to participate in this study; (2) history of allergies or severe reaction to vaccination; (3) known or anticipated immune dysfunction; (4) had previously received immune suppressive therapy (intravenous or oral cortisone or chemotherapy); (5) had previously received immunostimulation therapy; (6) high risk of becoming immunologically compromised; (7) history of hepatitis B vaccination; (8) history of any kind of vaccination within the previous four weeks; (9) had received any kind of observational or experimental drugs during the past four weeks; (10) acute illness within the past seven days; (11) infection that required treatment with antibacterial or antiviral therapy within the past seven days; (12) fever within the past three days (armpit temperature ≥38 °C); (13) HBsAg positive and/or anti-HBs positive.

2.2. Vaccines and vaccination

Subjects were assigned to one of four groups depending on the vaccine they were to receive: (1) Group I: hepatitis B vaccine (lot No. 20090521; dosage: 10 μg; produced by the Shenzhen Kangtai Biological Products Co., Ltd., China); (2) Group II: hepatitis B vaccine (lot Nos. 2009030906 and 2010010106; dosage: 10 μg; produced by the Dalian High-Tech Biopharmaceutical Co., Ltd., China); (3) Group III: hepatitis B vaccine (lot No. 200904A3101; dosage: 10 μg; produced by the North China Pharmaceutical Company, GeneTech Biotechnology Pharmaceutical Co., Ltd.) (Chinese Hamster Ovary (CHO)); (4) Group IV, the compared group, was given the foreign hepatitis B vaccine (lot No. XHBVB554AA; dosage: 10 μg; produced by the GlaxoSmithKline Company, UK).

We then administered hepatitis B vaccination by intramuscular injection in the upper deltoid muscle, according to the recommended immunization procedure at 0, 1, and 6 months.

2.3. Methods

Subjects were interviewed using the pre-designed questionnaire “Research Questionnaire on Adult Immunization Strategy of Hepatitis B”, which included information such as each patient’s date of birth, age, and gender. We collected 3 ml blood samples from each eligible HBsAg, anti-HBs, and anti-HBc negative subject prior to vaccination. Eligible subjects received three hepatitis B vaccinations. One month after the third vaccination, we collected 3 ml blood samples from each subject and preserved them for anti-HBs quantification.

2.4. Specimen collection and testing

We collected 3 ml blood samples from each subject and then froze the serum from the samples at −20 °C. The samples were sent to ADICON Clinical Laboratories Inc. in Hangzhou for HBsAg, anti-HBs and anti-HBc quantification by chemiluminescence immunoassay (CLIA). If the HBsAg and anti-HBs results did not match, samples were re-tested. Samples with an anti-HBs titer level greater than 15 000 mIU/ml were excluded from further dilution testing. An Architect-i2000 (Abbott, US) analyzer was used to perform the CLIA. The HBsAg test reagent lot number was 86040LF00, and a signal-to-noise ratio (S/N) ≥0.05 was considered to be positive. The anti-HBs test reagent lot number was 82521M100; an anti-HBs antibody level greater than or equal to 10 mIU/ml was considered to be positive and was defined as having protective effects against HBV infection. The anti-HBc test reagent lot number was 85276M500, and an anti-HBc antibody level greater than or equal to 1 mIU/ml was defined as positive.

2.5. Data collation and analysis

A database using EpiData3.2 (EpiData; Norway and Denmark) was established, and double data entry performed. Statistical analysis was performed using SPSS 13.0. A chi-square test or Fisher chi-square test was used for enumeration data, a U test was used for data that followed a normal distribution before or after logarithmic transformation, and a rank-sum test was used for data that did not follow a normal distribution. We used a two-tailed probability in statistical tests, with a P value of 0.05 considered to be significant.

3. Results

3.1. General information

Of the 2 600 subjects analyzed, 1 872 adults completed the immunization schedule and their blood serum was tested after completing the three vaccinations. Among these subjects, 771 were males whose average age was 32.59 years (95% confidence interval (CI): 32.01‒33.17) and whose median age was 32.33 years. There were 1 101 female subjects whose average age was 32.42 years (95% CI: 31.94‒32.91) and whose median age was 31.96 years. There were no statistically significant differences in age or gender among the four groups (Table (Table1;1; χ 2=1.555, P=0.670).

Table 1

Subject characteristics

3.2. Comparison of the anti-HBs positive seroconversion rate and the geometric mean titer (GMT) in different vaccines

The seroconversion rates of the three types of domestic vaccine were not significantly different from that of the foreign vaccine (χ 2=2.123, P=0.145). The anti-HBs-positive seroconversion rate was variable after the third dose of the different vaccines (χ 2=24.13, P<0.001). There were no statistically significant differences in the seroconversion rates between Group I and Group III (χ 2=3.30, P=0.069), Group I and the compared group (χ 2=0.06, P=0.81), or Group III and the compared group (χ 2=1.35, P=0.25). The Group II seroconversion rate was significantly higher than those of Group I (χ 2=23.00, P<0.001), Group III (χ 2=10.34, P=0.001), and the compared group (Table (Table2;2; χ 2=14.91, P<0.001).

Table 2

Anti-HBs positive seroconversion rate and GMT after the third dose of hepatitis B vaccine

There were no statistically significant differences in the GMTs between the three types of domestic vaccine and the foreign vaccine (t=−1.575, P=0.116). The GMTs of all groups were significantly different from each other (F=25.48, P<0.001).

3.3. Comparison of the anti-HBs positive seroconversion rate in different age groups after vaccination

Table Table33 shows that there were no significant differences among the different age groups (χ 2=8.576, P=0.073). In the three domestic vaccine groups, there were no significant differences in the positive seroconversion rate among the different age groups (χ 2=5.850, P=0.211), but there was a significant difference when these groups were compared with the foreign vaccine group (χ 2=11.546, P=0.021). The chi-square trend test also showed a significant decrease in the anti-HBs positive rate with increasing age (χ 2=4.940, P=0.026).

Table 3

Anti-HBs positive seroconversion rate in different age groups after vaccination

3.4. Comparison of the anti-HBs GMT in different age groups after vaccination

A total of 1 670 subjects were anti-HBs positive after vaccination, with a GMT of 271.95 mIU/ml. There was no significant difference in the anti-HBs GMT among the three domestic vaccines but the results for these vaccines were significantly different from those for the compared foreign vaccine (Table (Table4;4; F=5.139, P=0.001).

Table 4

Anti-HBs GMT distribution in different age groups

4. Discussion

Currently, hepatitis B vaccine is widely used to prevent HBV infection in China and abroad. The Advisory Committee on Immunization Practices (ACIP) proposed that non-immune adults should be encouraged to be immunized with the hepatitis B vaccine (Goldstein et al., 2005). An American report in 2007 showed that the highest proportion of new hepatitis B infections occurs in the 25 to 44 years old age group (Daniels et al., 2009). Vaccination for high-risk adults had already begun in USA in 1998 (Mast et al., 1998), and in 2006, adult hepatitis B vaccination was brought into the system of community primary health care and rehabilitation clinics (Mast et al., 2006). There were also immunization programs for high-risk adults in Britain and Italy (Bonanni, 1995; Zuckerman and Langer, 2005). The usual adult hepatitis B vaccine dose in China is 10 μg. There are three main types of hepatitis B vaccine in China: one is made by recombinant deoxyribonucleic acid (DNA) techniques in Hansenula polymorpha yeast, one is made by recombinant DNA techniques in CHO cells, and one is a recombinant hepatitis B vaccine (Saccharomyces cerevisiae). We chose all three for our research, as together they account for more than 90% of adult vaccinations. The results of this study indicated that high anti-HBs seroconversion rates and GMT were observed in adults who received the 10 μg immunization dose. It was also shown that good protective effects can be obtained using the 10 μg dose of the hepatitis B vaccine in China (Gong and Zhong, 2009; Yao and Chen, 2009).

The seroconversion rates of the different hepatitis B vaccine types indicated that the average anti-HBs seroconversion rate was 89.92% after vaccination with the three types of domestic 10 μg hepatitis B vaccines. This was not significantly different from that of the compared group whose anti-HBs seroconversion rate was 86.81%, which indicates that the immune effects of the different types of hepatitis B vaccines were consistent. These results are similar to those of Gong and Zhong (2009), Zhang et al. (2010), and others (Bryan et al., 1995; Rendi-Wagner et al., 2001). Gong and Zhong (2009) used 10 μg of hepatitis B vaccine made by recombinant DNA techniques in Saccharomyces cerevisiae yeast by the Beijing Tiantan Company. The seroconversion rate was 90.69%. They selected 873 HBsAg negative subjects.

Another study of 321 subjects, using 10 μg hepatitis B vaccine produced by the North China Pharmaceutical GeneTech Biotechnology Pharmaceutical Co., Ltd.) (CHO), had an 88.8% seroconversion rate. Factors such as smoking, drinking, and obesity were reportedly associated with immune failure, in addition to a strenuous job, stressful lifestyle, and mental pressure, which may overload the body and lead to a decline in immune function and thereby affect the seroconversion rate. The immune effect of the Dalian High-Tech 10 μg Hansenula hepatitis B vaccine was the best of the four types. Its seroconversion rate reached 95.05%, a rate significantly higher than those of the other three groups. This seroconversion rate was also similar to that of the 20 μg hepatitis B vaccine reported by Young et al. (2001). This similarity might be caused by the high purity of the Hansenula hepatitis B vaccine, which uses a chemosynthesis complete medium only, and not a selective medium, peptone or yeast powder. The seroconversion rates of the 10 μg hepatitis B vaccine produced by the North China Pharmaceutical Company and GlaxoSmithKline were slightly higher than that of the 10 μg hepatitis B vaccine previously reported by Young et al. (2001). Regarding the anti-HBs GMT, the immune effects for all the vaccines were good, except those of the Shenzhen Kangtai vaccine. These results suggest that the immune effects of the four hepatitis B vaccine types were good, and that they could provide good protection for the population. Considering the high anti-HBs seroconversion rate and GMT produced by the Dalian High-Tech vaccine, and considering that the persistence of immune protection would be extended as a result of the high GMT peak value (Jilg et al., 1988; Trivello et al., 1995; Yuan et al., 2003), we recommend the Dalian High-Tech vaccine.

An analysis of the hepatitis B vaccine immune effects in adults of different age groups was conducted. After dividing the subjects into five age groups, the relationship between the positive hepatitis B vaccine seroconversion rates and the subjects’ ages was analyzed. The results showed that there was no significant difference in the positive seroconversion rate for 10 μg hepatitis B vaccines among different adult age groups (χ 2=8.576, P=0.073). The chi-square trend test also showed a significant decrease in the anti-HBs positive rate with increasing age (χ 2=4.940, P=0.026). The positive anti-HBs seroconversion rates were different between the 10 μg hepatitis B vaccine produced by the North China Pharmaceutical Company and that produced by GlaxoSmithKline in the different vaccination age groups. There was a negative correlation (using the chi-square trend test) between the 10 μg hepatitis B vaccine produced by the North China Pharmaceutical Company and the subject’s age. These results indicate that the anti-HBs level attained after vaccination with hepatitis B vaccine was related to age, which was consistent with previous studies (Coates et al., 2001; Gilbert et al., 2011). There were no significant differences in the anti-HBs GMT among the three domestic vaccines but compared with the foreign vaccine, a significant difference was found (F=5.139, P=0.001). Overall, the study shows that vaccination of adults of different ages can result in good immune effects. The results of these studies provide good data in support of expanding immunization programs to adults.

After a long development, domestic hepatitis B vaccines have achieved some advantages, including a lower price compared to other hepatitis B vaccines. In our study, we selected three kinds of domestic vaccine and one foreign vaccine, and evaluated the immune effects of the four vaccines at the same time in a large-scale population. The results of this study confirm that there is little difference in the immune effects between the domestic hepatitis B vaccines (10 μg/dose) and the hepatitis B vaccine (10 μg) produced by GlaxoSmithKline. The immune effect of the hepatitis B vaccine produced by Dalian High-Tech was better than that of the hepatitis B vaccine produced by GlaxoSmithKline. Thus, the evidence supports the widespread use of domestic hepatitis B vaccine (Dong et al., 2009). The subjects involved in this study will be followed up closely, after one, three, and even five years. We believe this will provide useful scientific data of significance to China’s hepatitis B prevention and control programs.

Acknowledgments

We thank the Deqing center for disease control and prevention (CDC), Changxing CDC, Anji CDC, Wuxing CDC, Nanxun CDC, Tongxiang CDC, Shaoxing CDC, and relevant personnel.

Footnotes

*Project (No. 2009ZX10004-901) supported by the National Scientific and Technological Major Project of China

References

1. Bonanni P. Implementation in Italy of a universal vaccination programme against hepatitis B. Vaccine. 1995;13(s1):68–71. doi: 10.1016/0264-410X(95)80058-L. [PubMed] [Cross Ref]
2. Bryan JP, Craig PG, Reyes L, Hakre S, Jaramillo R, Harlan H, MacArthy P, Legters LJ. Randomized comparison of 5 and 10 microgram doses of two recombinant hepatitis B vaccines. Vaccine. 1995;13(11):978–982. doi: 10.1016/0264-410X(95)00030-5. [PubMed] [Cross Ref]
3. Chang MH, Hadzic D, Rouassant SH, Jonas M, Kohn IJ, Negro F, Roberts E, Sibal A. Acute and chronic hepatitis: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2004;39(s2):584–588. doi: 10.1097/00005176-200406002-00002. [PubMed] [Cross Ref]
4. Coates T, Wilson R, Patrick G, Andre F, Watson V. Hepatitis B vaccines: assessment of the seroprotective efficacy of two recombinant DNA vaccines. Clin Ther. 2001;23(3):392–403. doi: 10.1016/S0149-2918(01)80044-8. [PubMed] [Cross Ref]
5. Daniels D, Grytdal S, Wasley A. Surveillance for acute viral hepatitis—United States, 2007. MMWR Surveill Summ. 2009;58(3):1–27. [PubMed]
6. Dong MH, Lin YD, Qian YH, Jiang Y, Deng Y, Ding S, Ren YJ. Immunity effect of homemade recombinant yeast-derived hepatitis B vaccine in adults. Mod Med J China. 2009;11(2):24–26.
7. Ganczak M, Szych Z, Korzen M. Preoperative vaccination for HBV at Polish hospitals as a possible public health tool to limit the spread of the epidemic: a cross-sectional study. Vaccine. 2009;27(30):3969–3974. doi: 10.1016/j.vaccine.2009.04.042. [PubMed] [Cross Ref]
8. Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350(11):1118–1129. doi: 10.1056/NEJMra031087. [PubMed] [Cross Ref]
9. Gilbert CL, Klopfer SO, Martin JC, Schodel FP, Bhuyan PK. Safety and immunogenicity of a modified process hepatitis B vaccine in healthy adults ≥50 years. Hum Vaccin. 2011;7(12):1336–1342. doi: 10.4161/hv.7.12.18333. [PubMed] [Cross Ref]
10. Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol. 2005;34(6):1329–1339. doi: 10.1093/ije/dyi206. [PubMed] [Cross Ref]
11. Gong XY, Zhong JY. Evaluation of Immunogenicity of 10 μg Recombinant yeast-derived hepatitis B vaccine in adults. China Prevent Med. 2009;10(10):934–936. (in Chinese)
12. Jilg W, Schmidt M, Deinhardt F. Persistence of specific antibodies after hepatitis B vaccination. J Hepatol. 1988;6(2):201–207. doi: 10.1016/S0168-8278(88)80032-1. [PubMed] [Cross Ref]
13. Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107. doi: 10.1046/j.1365-2893.2003.00487.x. [PubMed] [Cross Ref]
14. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, et al. Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009;27(47):6550–6557. doi: 10.1016/j.vaccine.2009.08.048. [PubMed] [Cross Ref]
15. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, et al. Evaluation of the impact of hepatitis B vaccination among children born during 1992–2005 in China. J Infect Dis. 2009;200(1):39–47. doi: 10.1086/599332. [PubMed] [Cross Ref]
16. Lu FM, Zhuang H. Management of hepatitis B in China. Chin Med J (Engl) 2009;122(1):3–4. [PubMed]
17. Mast EE, Mahoney FJ, Alter MJ, Margolis HS. Progress toward elimination of hepatitis B virus transmission in the United States. Vaccine. 1998;16(Suppl.):48–51. doi: 10.1016/S0264-410X(98)00294-1. [PubMed] [Cross Ref]
18. Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, Rodewald LE, Douglas JM, Jr, Janssen RS, Ward JW. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). Part II: immunization of adults. MMWR Recomm Rep. 2006;55(RR-16):1–33. quiz CE31-CE34. [PubMed]
19. 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(15-16):2055–2060. doi: 10.1016/S0264-410X(00)00410-2. [PubMed] [Cross Ref]
20. Shen LZ, Yao J. Study development on booster immune strategy of hepatitis B vaccine. Zhejiang J Prevent Med. 2011;23(12):22–25. (in Chinese)
21. 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(2):139–141. doi: 10.1016/0264-410X(95)93126-T. [PubMed] [Cross Ref]
22. Weinbaum CM, Williams I, Mast EE, Wang SA, Finelli L, Wasley A, Neitzel SM, Ward JW. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1–20. [PubMed]
23. WHO (World Health Organization) Geneva, Switzerland: WHO; 2000. Hepatitis B. Available from http://www.who.int/mediacentre/factsheets/fs204/en. [Accessed on 2 June 2010]
24. Yao J, Chen YD. Immunity effect of domestic hepatitis B vaccine in adults. China Prevent Med. 2009;10(4):258–261. (in Chinese)
25. Yao J, Ren JJ, Shen LZ, Chen YD, Liang XF, Cui FQ, Li Q, Jiang ZG, Wang FZ. The effects of booster vaccination of hepatitis B vaccine on anti-HBV surface antigen negative children 11–15 years after primary vaccination. Hum Vaccin. 2011;7(10):1055–1059. doi: 10.4161/hv.7.10.15990. [PubMed] [Cross Ref]
26. Young MD, Gooch WM, 3rd, Zuckerman AJ, Du W, Dickson B, Maddrey WC. Comparison of a triple antigen and a single antigen recombinant vaccine for adult hepatitis B vaccination. J Med Virol. 2001;64(3):290–298. doi: 10.1002/jmv.1049. [PubMed] [Cross Ref]
27. Yuan YB, Zheng XH, Wang ZQ. Study on the immuno-effects and security of Chinese Hamster Ovary (CHO) cell hepatitis B vaccine among adults, under different dosages. Chin J Infect Dis. 2003;21(6):423–424. (in Chinese)
28. Zhang W, Lin C, Han L, Li L, Gao P, Lin H, Gong X, Huang F, Tang Y, Ma J. Study on the immuno-effects and influencing factors of Chinese Hamster Ovary (CHO) cell hepatitis B vaccine among adults, under different dosages. Chin J Epidemiol. 2010;31(7):767. (in Chinese) [PubMed]
29. Zuckerman J, Langer B. Hepatitis B vaccination in a school age population: a feasibility study. J Med Virol. 2005;76(1):47–54. doi: 10.1002/jmv.20335. [PubMed] [Cross Ref]

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