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The Wide World of Vaccines

June, 2018

New Improved Hepatitis B Vaccine for Adults – Should We Care?

Christopher J. Harrison, MD, FAAP, FPIDS | Director, Infectious Diseases Research Laboratory | Director, Vaccine and Treatment Evaluation Unit | Professor of Pediatrics

Most of us do not routinely think about the 5 percent of patients overall who do not achieve the seroprotective level (10mIU/ml) of antibody to hepatitis B surface antigen (anti-HBs) with hepatitis B vaccine. Higher failure rates also occur in special scenarios, i.e., wrong injection site or selected host factors (greater than 40 years old, male gender, obesity, smoking or chronic illness). But when faced with such a failure, revaccination and retesting is the norm. Revaccination should be in the deltoid muscle. But only 15-25 percent respond to one added dose and 30-50 percent to three added doses of conventional HepB vaccine (cHepB).1 One alternate approach has been higher vaccine doses, e.g., dialysis patients, but that has been only partially successful. Adding an adjuvant is a second alternative. An adjuvant can overcome the antigen unresponsiveness by in effect “turbo-charging” antigen-presenting cells and inducing a key T-cell enhancing cytokine, IL-12. Now an adjuvanted vaccine for those initial failures is FDA approved for adults. It may become a better choice for initial immunization of those at higher risk of cHepB failure, and someday hopefully for children.

Most initial failures occur due to incomplete/poor T-cell responses in a very antigen specific manner – i.e., being partially immunologically “blind” to the hepatitis B surface antigen. Therefore, a second series of vaccine using only surface antigen frequently fails again, and more importantly, these same “blind” patients appear more likely to develop chronic infection if they acquire hepatitis B virus. 

This new vaccine (Heplisav® - HepB-CpG) improves responsiveness using CpG, which activates toll-like receptor 9 (TLR-9), an inducer of interleukin-12 and interferon-alpha. CpG, a segment synthetic of DNA (cytosine phosphoguanine oligonucleotide (CpG 1018) is added to recombinant hepatitis B surface antigen. FDA approval of a two-dose schedule was based on 10 randomized controlled trials comparing HepB-CpG with a standard HepB vaccine (S-HepB - Engerix-B®). This February, ACIP made new recommendations for HepB-CpG for adults.

ACIP summary


Seroprotective titers occurred more often for 7,056 HepB-CpG subjects (two doses) vs. 3,214 S-HepB subjects (three doses). Table 1. (2–4).

Table 1. Comparison of Seroprotection Rate and Adverse Effects (AE) from a Conventional vs. an Adjuvanted Hepatitis B Vaccine.

 

 

HepB-CpG

Engerix®

Seroprotective response (%)

90-100

70.5-90.2

AE  (%)

45.6

45.7

Serious AE  (%)

5.4

6.3

Cardiac Event  (%)

0.27

0.12

AE= adverse event

Safety profiles for HepB-CpG revealed adverse effect rates were similar for both vaccines.3-6 So HepB-CpG is an option for hepatitis B vaccine in all persons 18 years and older. When feasible, use HepB-CpG vaccine to complete the series, but do not defer dosing if only S-HepB product is available. HepB-CpG is not yet recommended for pregnant women needing HepB vaccination.
  

Postvaccination serologic testing


Those with anti-HBs less than 10 mIU/mL after two HepB-CpG doses need revaccination the same as for prior hepatitis B vaccines, i.e., another complete series. An alternate option is one added dose and then retest. If anti-HBs remains less than 10 mIU/mL, give the second dose of HepB-CpG followed by testing again one to two months post second dose.

Use in health care workers (HCW) 


HepB-CpG may be used to initially vaccinate new HCW or those who have anti-HBs less than 10 mIU/mL after vaccination with a vaccine, other than HepB-CpG, either recently or in the distant past.2 
So if you have need to revaccinate an adult who failed HepB vaccine, HepB-CpG seems the best option. Hopefully future data will allow us to use it also in children.

References:

1. CDC. Prevention of Hepatitis B virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018;67(No. RR-1).
2. CDC – ACIP Recommendations for HepB-CpG 2018. https://www.cdc.gov/vaccines/schedules/vacc-updates/heplisav-b.pdf
3. Comparison of the Safety and Immunogenicity of Hepatitis B Virus Surface Antigen Co-administered with an Immunostimulatory Phosphorothioate Oligonucleotide and a Licensed Hepatitis B Vaccine in Healthy Young Adults. Halperin SA, Dobson S, McNeil S, et al. Vaccine 2006;24:20–6. https://doi.org/10.1016/j.vaccine.2005.08.095 
4. Immunogenicity and Safety of an Investigational Hepatitis B Vaccine with a Toll-like Receptor 9 Agonist Adjuvant (HBsAg-1018) Compared to a Licensed Hepatitis B Vaccine in Healthy Adults 40–70 Years of Age. Heyward WL, Kyle M, Blumenau J, et al. Vaccine 2013;31:5300–5. https:// doi.org/10.1016/j.vaccine.2013.05.06
5. 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. Jackson S, Lentino J, Kopp J, et al.; HBV-23 Study Group. Vaccine 2018;36:668–74. https://doi.org/10.1016/j.vaccine.2017.12.038 
6. Demonstration of Safety and Enhanced Seroprotection Against Hepatitis B with Investigational HBsAg-1018 ISS Vaccine Compared to a Licensed Hepatitis B Vaccine. Sablan BP, Kim DJ, Barzaga NG, et al. Vaccine 2012;30:2689–96. https://doi.org/10.1016/j.vaccine.2012.02.001 
7. Immunogenicity of an Investigational Hepatitis B vaccine (Hepatitis B Surface Antigen Co-administered with an Immunostimulatory Phosphorothioate Oligodeoxyribonucleotide) in Nonresponders to Licensed Hepatitis B Vaccine. Halperin SA, Ward BJ, Dionne M, et al. Hum Vaccin Immunother 2013;9:1438–44. https://doi. org/10.4161/hv.24256