Study Compares 2-Dose Versus 3-Dose Hepatitis B Vaccine in Older Patients With Type 2 Diabetes

The immunogenicity and safety of hepatitis B surface antigen (HBsAg)/CpG 1018 was assessed in patients with diabetes aged 60 to 70 years.

Hepatitis B surface antigen (HBsAg)/CpG 1018 (Heplisav-B), a 2-dose hepatitis B virus (HBV) vaccine, provides higher seroprotection against HBV than 3-dose HBsAg/alum (Engerix-B) in older patients with type 2 diabetes, according to a study published in Vaccine.

The World Health Organization currently estimates that 257 million individuals are seropositive for HBsAg. Adults with diabetes are typically at higher risk of contracting HBV than the general population and have more severe HBV-related morbidity. However, approximately 90% of individuals with diabetes who are aged 60 years or older remain unvaccinated for HBV, according to the study authors.

Given that diabetes is most prevalent in adults in this age group, there is a challenge for this population who is at increasing risk for HBV infection and who do not respond well to traditional 3-dose, alum-adjuvanted vaccines, according to the authors.

“Improved HBV vaccines that demonstrated higher and earlier seroprotection in older adults with [diabetes mellitus] may help address this growing public health problem,” they wrote in the study.

For the study, the authors assessed the safety and efficacy of HBsAg/CpG 1018 among adults with type 2 diabetes who are aged 60 to 70 years old compared with HBsAg/alum. Immunogenicity, including seroprotection (SPR) at week 28, and safety were assessed by subgroup. SPR was defined as antibody against HBsAg serum concentration ≥10 mIU/mL. Patients received either HBsAg/alum at weeks 0, 4, and 24 or HBsAg/CpG 1018 at weeks 0 and 4 and placebo at week 24.

At week 28, SPR was significantly higher with HBsAg/CpG 1018 (85.8% [235/274] than with HBsAg/alum (58.5% [76/130] in the per-protocol analysis, for an overall difference of 27.3 (95%. CI, 18.0-36.8), according to the study.

SPRs with HBsAg/CpG 1018 were consistently markedly higher compared with HBsAg/alum, regardless of sex, body mass index, or smoking status subgroup.

Additionally, the results also indicated that the safety profile of the 2-dose HBsAg/CpG 1018 vaccine is similar to that of a commonly used 3-dose vaccine. The findings of this analysis are consistent with results from the overall phase 3 study population and several previous phase 3 studies of HBsAg/CpG.

According to the authors, future studies are needed to determine the potential benefits of administering the 2-dose vaccine to patients with type 2 diabetes who are older than 70 years of age.

“Our findings suggest careful consideration of the potential benefits of administering the 2-dose HBsAg/CpG 1018 vaccine to protect against HBV in patients with type 2 [diabetes mellitus] who are aged 60-70 years and to other traditionally hyporesponsive and at-risk individuals including men, people with obesity, and smokers,” the authors concluded.


Janssen RS, Hyer RN. Immunogenicity and safety of a 2-dose hepatitis B vaccine, HBsAg/CpH 1018, in persons with diabetes mellitus aged 60-70 years. Vaccine. 2019.