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Hepatitis B Vaccine in Older Individuals with Type 2 Diabetes

By Lourdes Cross posted 06-18-2021 16:00


Hepatitis B Vaccine in Older Individuals with Type 2 Diabetes
Lourdes Cross, PharmD, BCACP, CDCES

Key Takeaways

  • HBsAg/CpG (Heplisav-B) is a single-antigen hepatitis B vaccine with a immunostimulatory sequence adjuvant administered as 2 doses, 1 month apart.
  • HBsAg/CpG provides higher rates of seroprotection against hepatitis B virus versus 3-dose HBsAg/alum (Engerix-B) in patients aged 60-70 years with type 2 diabetes.
  • Adverse events and deaths are comparable in both groups.


Although hepatitis B is a vaccine-preventable disease, hepatitis B virus (HBV) infection remains a major public health issue. Adults with diabetes are at a higher risk of contracting HBV than the general population and have more severe HBV-related morbidity. Commonly used 3-dose HBV vaccines have less immunogenicity in older individuals and in those with diabetes.1,2 Moreover, approximately 90% of individuals with diabetes who are older than 60 years are not vaccinated.3 A study published in Vaccine compared participants with type 2 diabetes (T2D) aged 60-70 years who received either 2-dose HBsAg/CpG (Heplisav-B) or 3-dose HBsAg/alum (Engerix-B).4

Methods and Results

In this post hoc analysis of a phase 3 clinical trial, individuals received either 2-dose HBsAg/CpG (Heplisav-B, n = 327) at 0 and 4 weeks and placebo at 24 weeks or 3-dose HBsAg/alum (Engerix-B, n = 153) at 0, 4, and 24 weeks. Seroprotection, defined as antibody against HBsAg serum concentration ≥10 mIU/mL, and safety were assessed at week 28. Results show that seroprotection was significantly higher with HBsAg/CpG (85.8%) than with HBsAg/alum (58.5%) in the per-protocol analysis, for an overall difference of 27.3 (95%. CI, 18.0-36.8).

The overall safety of HBsAg/CpG was comparable to that of HBsAg/alum regardless of smoking status, body mass index, or gender. A total of 210 (64.2%) individuals in the HBsAg/CpG group reported a major adverse event (most commonly reported events: upper respiratory tract infection [5.5%], back pain [4.0%], bronchitis [3.7%], urinary tract infection [3.7%]). In the HBsAg/alum group, 85 (55.6%) participants experienced MAEs (most commonly reported events: worsening of T2D [5.2%], back pain [4.6%], bronchitis [4.6%], and sinusitis [3.9%]). No serious events related to the study treatment were reported in either group.


Seroprotection rates after administration of commonly used 3-dose HBV vaccines steadily decrease with increasing age. In 2018, the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) recommended HepB-CpG for use in persons aged ≥18 years.5 The ACIP specifically state that the hepatitis B vaccine should be given in people with diabetes aged <60 years and people with diabetes aged ≥60 years at the discretion of the treating clinician. However, low rates of adherence to these guidelines in people with diabetes persist.

This study demonstrates that 2-dose HBsAg/CpG (Heplisav-B) provides higher seroprotection against HBV than 3-dose HBsAg/alum (Engerix-B) in older patients with T2D with no significant difference in adverse effects. The immunogenicity and safety findings of this study are consistent with results from the overall phase 3 study population and several previous phase 3 studies of HBsAg/CpG.6–9 Therefore, the potential benefits of 2-dose HBsAg/CpG (Heplisav-B) may apply to older patients with T2D and to other traditionally hyporesponsive and at-risk individuals including men, people with obesity, and smokers.


  1. Van Der Meeren O, Peterson JT, Dionne M, et al. Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus. Hum Vaccin Immunother. 2016;12(8):2197-2203. doi:10.1080/21645515.2016.1164362
  2. Yang S, Tian G, Cui Y, et al. Factors influencing immunologic response to hepatitis B vaccine in adults. Sci Rep. 2016;6:27251. doi:10.1038/srep27251
  3. Williams WW, Lu P-J, O’Halloran A, et al. Surveillance of Vaccination Coverage among Adult Populations - United States, 2015. MMWR Surveill Summ. 2017;66(11):1-28. doi:10.15585/mmwr.ss6611a1
  4. Hyer RN, Janssen RS. Immunogenicity and safety of a 2-dose hepatitis B vaccine, HBsAg/CpG, in persons with diabetes mellitus aged 60-70years. Vaccine. 2019;37(39):5854-5861. doi:10.1016/j.vaccine.2019.08.005
  5. Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67(15):455-458. doi:10.15585/mmwr.mm6715a5
  6. Schillie SF, Spradling PR, Murphy T V. Immune response of hepatitis B vaccine among persons with diabetes: a systematic review of the literature. Diabetes Care. 2012;35(12):2690-2697. doi:10.2337/dc12-0312
  7. Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36(5):668-674. doi:10.1016/j.vaccine.2017.12.038
  8. Janssen JM, Jackson S, Heyward WL, Janssen RS. Immunogenicity of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in subpopulations of healthy adults 18-70 years of age. Vaccine. 2015;33(31):3614-3618. doi:10.1016/j.vaccine.2015.05.070
  9. Janssen JM, Heyward WL, Martin JT, Janssen RS. Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease and type 2 diabetes mellitus. Vaccine. 2015;33(7):833-837. doi:10.1016/j.vaccine.2014.12.060