HEPATITIS B vaccination - Immunization
Last Updated : 6/29/2016
Wanke-Rytt Monika & Kuchar Ernest
The vaccine against hepatitis B virus
The vaccine against hepatitis B virus which provides active immuno-prophylaxis against hepatitis B was introduced by the Merck, Sharp and Dohme pharmaceutical company in the USA in 1981. The current vaccine is 95% effective in preventing infection and the development of chronic liver disease and liver cancer due to hepatitis B. The individual hepatitis B vaccine can be given alone or at the same time as other vaccines such as PCV, hepatitis A, MMR, MenC, rotavirus, pre-school booster. When immunising against HBV at birth, only monovalent HBV vaccine should be used. It was a first generation, plasma-derived vaccine, in which the vaccine antigen was the HBV surface antigen (HBsAg) coating the viral particle. The protein parts containing the HBsAg isolated from the blood of patients infected with HBV were subject to virus inactivation procedures before they were included in the vaccine. The second generation vaccine made commercially available was developed in 1986 by SmithKline Beecham (now known as GlaxoSmithKline) from Belgium. It used recombinant DNA technology and involved insertion of plasmid-encoded HBsAg gene sequence into Saccharomyces cerevisiae yeast cells. The synthesis of HBsAg in rapidly proliferating yeast cells constitutes a potentially infinite source for production of vaccine material. The recombinant HBsAg is currently used as a vaccine antigen against hepatitis B in both monovalent and combined vaccines. Overall, approximately 1 billion vaccines against the virus have been administered in the years 1981-1999. The vaccines available on the market differ in: yeast species used for the manufacture of HBsAg, HBsAg content, contained preservatives, and vaccination schedules. The efficiency of vaccines against hepatitis B is >90% making the global eradication of HBV feasible in the future (6). According to the available statistical data, in 2011, 76.8% of the population received vaccination in comparison to 3% in 1992 (6). There are monovalent or combined vaccines available on the market; bivalent vaccines provide protection against hepatitis A and B and are recommended mainly for adults travelling abroad. Other combination vaccines such as 5-in-1 and 6-in-1 are administered to infants.

Routine vaccination of infants
The hepatitis B vaccine is recommended for all infants born to HBsAg-positive mothers and in many countries also for all infants whose mothers are HBsAg-negative (7). The time of the first dose depends on the HBsAg status of the mother, gestational age and birth weight (7). The recommended vaccination schedule is shown in Table 1. Only the monovalent vaccine may be used after child’s birth whereas from 2 months of age the second and third vaccine dose can be given in a form of either a monovalent or conjugated vaccine. Infants who received the monovalent vaccine after birth can be administered the conjugate vaccine, thereby obtaining 4 doses. This schedule has not been found to impact vaccine efficiency or the immune response (7). In the case of infants born to mothers who tested negative for HBs, according to the recommended vaccination schedule in many European countries, the first dose should be administered after the first month of age (7).
The routine infant vaccinations aim to eradicate the HBV infections. In many countries the universal immunisations have significantly reduced not only the HBV carrier status over the years, but also later complications of hepatitis B infections such as cirrhosis and hepatocellular carcinoma. For example, in 1984 in Taiwan vaccination was initially introduced for babies born to carrier mothers, but in 1986 the schedule included all babies. Before introduction of vaccination, the percentage of HBs-positive children (carriers) in patients below 15 years of age was 9.8% and the incidence of liver cancer varied from 1.02 to 0.48 per 100 000 births depending on gender (8). Twenty years later, the carrier state in the same age group dropped to 1.2% and continues to diminish significantly. A similar decreasing trend concerning the incidence of hepatocellular carcinoma is being observed in vaccinated individuals (8).
Infants born to HBsAg-positive mothers. Vaccination of babies born to infected mothers plays a crucial role in the eradication of HBV infections (7). The risk of vertical transmission is high and amounts approximately 90-95% without immunoprophylaxis (9). The standard procedure involves concurrent active and passive immunization i.e. vaccination and administration of anti-HBs immunoglobulins at birth, regardless of body weight (7). It has been shown that vaccination and immunoglobulin administration up tp 12 hours after birth, as well as two subsequent vaccine doses in the first year of age, have a high efficiency of 95% (7). Preventative measures based on passive immunization only, have a much lower efficiency of 75 - 80% and should not be used (10). Furthermore, children who received 3 doses of vaccine should undergo serological testing (HBsAg and anti-HBs) (7). In October 2015, the US Center for Disease Control and Prevention (CDC) shortened the recommended time interval between the last vaccine dose and serologic testing. Instead of testing at the age of 18 months, now it is advised to test children who are at age 9 through 12 months (11). This change was dictated by the results of observational studies indicating that the anti-HBs titres continued to decrease with time between vaccination and testing, resulting in unnecessary administration of additional boosters. It should be noted that the serological test should not be done before age 9 months due to the presence of the immunoglobulin given at birth. The test should neither be performed earlier than 4 weeks after the last vaccine dose due to possible false HBs-positive results (7,10). Children who do not respond to vaccination should have the three-dose series (0-1-6) repeated and checked for the HBs antigen. Children who despite these two series of vaccinations did not respond properly are referred to as ‘non-responders’ (7).

Preterm infants
It has been proven that the first dose of the vaccine in children with birth weight <2000 g induces a weaker response, hence the World Health Organization (WHO) recommend the 0, 1, 2, 12 months schedule (12). However, different recommendations were issued by the American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) which allow either administration of the 1 dose when the child is age 1 month, or discharge from the hospital, but only in if mother is HBs-negative (7, 13). The data shows that premature infants with birth weight >2 kg respond to vaccination as well as children born on their due date (7).

Table 1. Recommended schedule of hepatitis B immunoprophylaxis for term infants and preterm infants with birth weight 2 kg (5)
Maternal HBsAg status Single-antigen vaccine Single antigrn + combination vaccine
Dose Age Dose Age
Positive 1 Birth (<12h) 1 Birth (<12h)
HBIG Birth (<12h) HBIG Birth (<12h)
2 1 to 2 months 2 2 months
3* 6 months** 3 4 months
    4* 6 months**
Unknown*** 1 Birth (<12h) 1 Birth (<12h)
2 1 to 2 months 2 2 months
3* 6 months 3 4 months
    4* 6 months
Negative 1 Birth (before discharge) 1**** Birth (before discharge)
2 1 to 2 months 2 2 months
3* 6 to 18 months 3 4 months
    4* 6 months
HBIG: hepatis B immune globulin
* The final dose in the vaccine series should be administrated before age 24 weeks
** These infants should be tasted for antibody to HBsAG (anti-HBs) and HBsAg at age 9 to 12 months or 1 to 2 months after the last dose of the hepatitis B vaccine. Testing should be performer before age 9 months nor within 4 weeks of the most recent vaccine dose
*** Mothers should have blood frawn and tasted for HBsAg as soon as possible after admission for delivery
****On a case-by-case basis and only in rare circumstanses, the first dose may be delayed until after hospital discharge for an infant who weights > 2000g and whose mother is HBsAg negative, but only if a clinician’s order to withhold the birth dose and a copy of the mother’s original HBsAg-negative laboratory report are documented in the infant’s medical record

Assessment of post-vaccination response
Evaluation of antibody levels after vaccination for hepatitis B is recommended only in certain cases which are listed below (1):
• Infants born to HBsAg-positive mothers – should be tested for both HBsAg and anti-HBs mostly at age 9 through 18 months after 3 doses or 1 to 2 months after the last dose.
• Haemodialysed patients - due to the possible decreased response to the vaccine, their antibody titre should be determined 1 - 2 months after the last dose in order to plan possible revaccination. ACIP and AAP recommend annual testing of anti-HBs if the anti-HBs level declines to <10 mIU / mL a booster is recommended.
• Immunocompromised patients - ACIP and AAP recommend annual testing of response to vaccination if the anti-HBs level declines to <10 mIU/mL administration of a booster dose should be considered.
• Sexual partners of HBV carriers

As shown above, the vaccine against hepatitis B is an effective, safe and cost-effective medical intervention which prevents hepatitis B infections. Despite this fact, there are several European countries (Great Britain and the Scandinavian countries) which do not have universal and compulsory vaccinations. These countries justify their decision by explaining that hepatitis B infection does not constitute a common problem there, therefore there is no indication to bear the financial burden of universal vaccination (16). In the developing countries, the faced financial problems and the need to strive for sanitation, hygiene policy, access to clean water and food have priority over the introduction of universal vaccination.


Contributor Information and Disclosures

Wanke-Rytt Monika & Kuchar Ernest
Department of Pediatrics with Clinical Assessment Unit,
Medical University of Warsaw, Poland

First Created : 6/29/2016
Last Updated : 6/29/2016


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