Immunogenicity and safety of a high-dose hepatitis B vaccine among patients receiving methadone maintenance treatment: A randomized, double-blinded, parallel-controlled trial.
To explore whether the immunization with high-dose (60μg) hepatitis B vaccines in patients receiving methadone maintenance treatment (MMT) could yield a superior protection against hepatitis B infection than did the standard dose (20μg).



We conducted a randomized, double-blinded, parallel-controlled trial in MMT patients. Patients with serologically negative hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were randomized in a ratio of 1:1 to receive three intramuscular injections of 20μg or 60μg recombinant hepatitis B vaccine at months 0, 1, and 6. Serum HBsAg and anti-HBs were measured at months 7 and 12 post-vaccination to assess the immunogenicity.



A total of 196 MMT patients were randomized and 195 received at least one injection (98 and 97 in 20 and 60μg vaccine groups, respectively). The 60μg vaccine group showed a seroconversion of anti-HBs of 87.3%, high-level response rate of 56.3%, and GMC of 742.9mIU/mL at month 7. While these results were numerically higher than the 20μg group, a statistical difference was not found. HIV infection and concomitant drug abuse were negatively associated with the robust immune responses. 7.7% of MMT patients receiving at least one dose of vaccine reported solicited adverse reactions within 7days after vaccination, 2.6% reported unsolicited adverse reactions within 28days after vaccination. None of the MMT patients reported serious adverse events or became HBsAg positive during the follow-up.



The three-dose regimen of 60μg recombinant hepatitis B vaccine at months 0, 1, and 6 can yield a similar immunogenicity among MMT patients as compared to the 20μg vaccine. ClinicalTrials.gov identifier: NCT02991599.
School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Jing
J
Shi
School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Yongliang
Y
Feng
School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Linying
L
Gao
School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Dan
D
Feng
School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Tian
T
Yao
Methadone Maintenance Treatment Clinic, Nanning Red Cross Hospital, Nanning, Guangxi, China.
Shan
S
Shi
Yale School of Medicine, New Haven 06510, CT, USA.
Yawei
Y
Zhang
Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Xiaofeng
X
Liang
School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China. Electronic address: spwang88@163.com.
Suping
S
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D060046:Maintenance Chemotherapy; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D055815:Young Adult
D000701:Analgesics, Opioid; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D008691:Methadone
Hepatitis B vaccination; Injections; Intramuscular; Methadone maintenance treatment; Randomized controlled trial