What is Hepatitis B Vaccine?
There are six recombinant hepatitis B vaccines approved by the FDA for use in the U.S.: Engerix-B; Recombivax HB; Twinrix (combined with hepatitis A); Pediarix (combined with diphtheria and tetanus toxoids, acellular pertussis adsorbed, and inactivated poliovirus); and HEPLISAV-B, recombinant adjuvanted vaccine, recommended for use in adults by the CDC in 2018.1 HEPLISAV-B, a recombinant, adjuvanted hepatitis B vaccine created through genetic engineering of DNA by inserting a segment of the viral gene in a yeast cell,2 also contains the CpG 1018 adjuvant, not previously used in any vaccine licensed in the U.S.3 A sixth vaccine, VAXELIS, a 6 in 1 combination vaccine containing diphtheria and tetanus toxoids, acellular pertussis adsorbed, inactivated poliovirus, hepatitis B recombinant, and Hib conjugate vaccine, received FDA approval in December 2018.4 VAXELIS is expected to be available for use in the United States in 2020,5 however, at this time the CDC’s Advisory Committee on Immunization Practice (ACIP) has not made any recommendation regarding the use of VAXELIS.
Recombivax HB – According to Merck, Recombivax HB is a recombinant hepatitis B vaccine approved by the FDA for intramuscular administration in both infants and adults. It is derived from hepatitis B virus surface antigen (HBsAg) produced in yeast cells. A portion of the hepatitis B virus gene is cloned into yeast, and the vaccine for hepatitis B is produced from cultures of this recombinant yeast strain using proprietary methods developed in the Merck research laboratories. The antigen is collected and purified from fermentation cultures of a recombinant strain of the yeast Saccharomyces cerevisiae containing the gene for the adw subtype of HBsAg. This fermentation process involves growth of Saccharomyces cerevisiae on a complex fermentation medium which consists of an extract of yeast, soy peptone, dextrose, amino acids and mineral salts. The HBsAg protein is released from the yeast cells by cell disruption and purified. This purified protein is treated in phosphate buffer with formaldehyde and then coprecipitated with potassium aluminum sulfate and amorphous aluminum hydroxyphosphate sulfate to form the vaccine adjuvant. Each dose of Recombivax HB should contain no more than one percent yeast protein. The vial stopper and the syringe plunger stopper and tip cap contain dry natural latex rubber, which may cause allergic reactions in latex-sensitive individuals.
Recombivax HB is supplied in three formulations. The pediatric/adolescent formulation (approved for birth to age 19) contains 5 mcg of hepatitis B surface antigen in each 0.5ml dose. Adult formulation (> age 20), contains 10 mcg of hepatitis B surface antigen. The dialysis formulation contains 40 mcg of hepatitis B surface antigen in each 1 mL dose.
All formulations contain approximately 0.5 mg of amorphous aluminum hydroxyphosphate sulfate per mL of vaccine. In each formulation, hepatitis B surface antigen is adsorbed onto approximately 0.5 mg of amorphous aluminum hydroxyphosphate sulfate per mL of the vaccine. Recombivax HB contains yeast protein, soy peptone, dextrose, amino acids, mineral salts, potassium aluminum sulfate, amorphous aluminum hydroxyphosphate sulfate, formaldehyde, phosphate buffer. A series of three doses of the Recombivax HB vaccine is recommended on a one, two and six month schedule.
Animal reproduction studies have not been conducted and it is unknown whether the vaccine can cause fetal harm or affect reproduction. It has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility.6
Engerix B – According to GlaxoSmithKline, Engerix B is a recombinant hepatitis B vaccine approved by the FDA for intramuscular administration in both infants and adults. It is comprised of a suspension of hepatitis B virus surface antigen (HBsAg) and contains purified surface antigen of the hepatitis B virus obtained by culturing genetically engineered Saccharomyces cerevisiae cells (yeast cells), which carry the surface antigen gene of the hepatitis B virus. The HBsAg expressed in the cells is purified and adsorbed on aluminum hydroxide. Engerix B should contain no more than 5 percent yeast protein. The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.
Each 0.5-mL pediatric/adolescent (birth through age 19) dose contains 10 mcg of HBsAg on 0.25 mg aluminum hydroxide. Each 1 mL adult (> age 20) dose contains 20 mcg of HBsAg adsorbed on 0.5 mg aluminum hydroxide. Engerix B also contains sodium chloride, disodium phosphate dihydrate and sodium dihydrogen phosphate dihydrate. A series of three doses of the Engerix B is recommended on a one, two and six month schedule.
Animal reproduction studies have not been conducted and it is unknown whether the vaccine can cause fetal harm or affect reproduction. It has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility.7
Twinrix - According to GlaxoSmithKline, Twinrix Hepatitis A & Hepatitis B (Recombinant) Vaccine contains the antigen components used to produce Havrix (Hepatitis A Vaccine) and Engerix B Hepatitis B Vaccine (Recombinant). Twinrix is administered intramuscularly and contains inactivated hepatitis A virus (strain HM175) and noninfectious hepatitis B virus surface antigen (HBsAg). The hepatitis A virus is propagated in MRC-5 human diploid cells and inactivated with formalin. The HBsAg is obtained by culturing genetically engineered Saccharomyces cerevisiae yeast cells that contain the surface antigen gene of the hepatitis B virus. Bulk preparations of each antigen are adsorbed onto aluminum salts and then pooled during formulation. The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.
Each 1-mL dose of the vaccine contains 720 ELISA Units of inactivated hepatitis A virus and 20 mcg of recombinant HBsAg protein. It also contains 0.45 mg of aluminum in the form of aluminum phosphate and aluminum hydroxide as adjuvants, amino acids, sodium chloride, phosphate buffer, polysorbate 20, MRC-5 (human diploid cells) proteins, neomycin sulfate, residual formalin, yeast protein and water for Injection.
Animal reproduction studies have not been conducted and it is unknown whether the vaccine can cause fetal harm or affect reproduction. It has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility.
Twinrix is approved in adults > 18 years of age and administered in a series of three doses on a one, two and six month schedule. It is also approved for an accelerated four dose series to be administered on days 0, 7, 21 to 30 with a booster at 12 months.8
Pediarix – According to GlaxoSmithKline, Pediarix and contains Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine.
Each 0.5 mL dose is formulated to contain 25Lf of diphtheria toxoid, 10 Lf of tetanus toxoid, 25 mcg of inactivated pertussis toxin (PT), 25 mcg of filamentous hemagglutinin (FHA), 8 mcg of pertactin( 69 kiloDalton outer membrane protein), 10 mcg of HBsAg, 40 D-antigen Units (DU) of Type 1 poliovirus (Mahoney), 8DU of Type 2 poliovirus (MEF-1), and 32 DU of Type 3 poliovirus (Saukett). The diphtheria, tetanus, and pertussis components are the same as those in Infanrix and Kinrix. The hepatitis B surface antigen (HBsAg) is the same as that in Engerix B.
Each 0.5 mL dose contains formaldehyde, glutaraldehyde, aluminum hydroxide, aluminum phosphate, lactalbumin hydrolysate, polysorbate 80, neomycin sulfate, polymyxin B, yeast protein, calf serum, Fenton medium (containing bovine extract), modified Latham medium (derived from bovine casein), modified Stainer-Scholte liquid medium and Vero (monkey kidney) cells.
The tip caps of the prefilled syringes contain natural rubber latex.
Pediarix is approved for use as a three-dose series in infants born of hepatitis B surface antigen (HBsAg)-negative mothers. Pediarix may be given as early as six weeks of age through six years of age (prior to the 7th birthday).9
HEPLISAV-B – According to Dynavax, HEPLISAV-B is a preservative free, .05 mL single dose vial vaccine adjuvanted with 3,000 mcg of CpG 1018, and also contains 20 mcg of HBsAg (recombinant Hansenula polymorpha yeast), sodium phosphate, sodium chloride, and polysorbate 80. Vial stoppers are not made with natural rubber latex.10
HEPLISAV-B was approved in 2018 for use in the U.S. for use in adults 18 years of age and older as and intramuscular two dose injection series spaced one month apart.11
There are no clinical studies of HEPLISAV-B in pregnant women and it is not known if the vaccine is excreted in breast milk, or would have an impact milk production or breastfed infants. HEPLISAV-B has not been studied for carcinogenic or mutagenic potential, or for impairment of fertility. Animal data on female rats showed no adverse impacts prior to mating, pre and post natal development up to the time of weaning, and no fetal malformations. There are also no clinical data on this vaccines use in children and adults on hemodialysis. 12
VAXELIS is manufactured in partnership by Sanofi Pasteur and Merck (MCM Vaccine Company) and contains Diphtheria and Tetanus Toxoids and Acellular Pertussi Adsorbed, Inactivated Poliovirus, Haemophilus influenzae type b, and Hepatitis B recombinant. According to the manufacturer’s product insert, each 0.5 mL dose of VAXELIS is formulated to contain 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, acellular pertussis antigens, 20 mcg detoxified pertussis toxin (PT), 20 mcg filamentous hemagglutinin (FHA), 3 mcg pertactin (PRN), 5 mcg fimbriae types 2 and 3 (FIM), inactivated polioviruses (29 D-antigen units (DU) Type 1 Mahoney, 7 DU Type 2 MEF-1, 26 DU Type 3 Saukett, 3 mcg polyribosylribitol phosphate (PRP) of H. influenzae type b bound to 50 mcg of the outer membrane protein complex (OMPC) of Neisseria meningitidis serogroup B, and 10 mcg hepatitis B surface antigen (HBsAg). Each 0.5 mL dose of VAXLEIS contains 319 mcg of aluminum salts as an adjuvant.
Additional ingredients in each 0.5ml dose of VAXELIS includes 319 mcg of aluminum salts as the adjuvant, <0.0056 percent polysorbate 80, less than or equal to 14 mcg residual formaldehyde, less than or equal to 50 ng residual glutaraldehyde, less than or equal to 50 ng residual residual bovine serum albumin, less than 25 ng of polymyxin B sulfate, less than 5ng of neomycin, less than 200ng of streptomycin sulfate, less than or equal to 0.1ng yeast protein, and less than or equal to 0.125 ng ammonium thiocyanate. VAXELIS does not contain any preservatives.13
VAXELIS is approved for use in infants and children ages 6 weeks through 4 years of age (prior to the fifth birthday). It is injected into the muscle in a 3-dose schedule and recommended to be administered at 2, 4, and 6 months of age.14 Currently, the CDC’s Advisory Committee on Immunization Practices has not made any recommendation regarding the use of VAXELIS. VAXELIS is expected to become available in the United States in 2020.15
The CDC recommends that all infants 4.4 lbs and greater born to HBsAg-negative mothers be vaccinated with the first dose of hepatitis B vaccine within 24 hours of birth. Infants weighing less than 4.4 lbs born to HBsAg-negative mothers should have the hepatitis B vaccine delayed until hospital discharge or one month of age. The final dose of hepatitis B vaccine should not be administered prior to 24 weeks of age. In populations with high rates of hepatitis B, vaccination with hepatitis B is recommended at birth, with the final dose recommended to be administered between 6 and 12 months of age. Infants born to HBsAg-positive mothers are recommended to receive hepatitis B vaccine, along with hepatitis B immune globulin (HBIG) within 12 hours of birth. The CDC also recommends hepatitis B vaccination for adults with diabetes; household and sexual contacts of people with chronic hepatitis B infection; healthcare workers; people at increased risk for hepatitis B virus exposure due to occupational, behavioral, or medical factors; and international travelers to countries with high or intermediate hepatitis B infection rates.16
The hepatitis B Surface Antibody (anti-HBs) blood test can determine whether a person has immunity to Hepatitis B, however, this test is unable to differentiate between vaccine induced immunity or recovery from an acute infection. 17
IMPORTANT NOTE: NVIC encourages you to become fully informed about Hepatitis B and the Hepatitis B vaccine by reading all sections in the Table of Contents , which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.
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1 FDA. Vaccines, Blood & Biologics. Complete List of Vaccines Licensed for Immunization and Distribution in the U.S. Nov.16, 2018.
2 CDC. Vaccines: The Pink Book. Principles of Vaccination. 13th Edition. 2015.
3 FDA. Hepatitis B Vaccine (Recombinant), Adjuvanted (HBV Surface Antigen (HBsAg) Protein with CpG 1018 adjuvant). Jul. 28. 2017
4 FDA December 21, 2018 Approval Letter- VAXELIS Dec. 21, 2018
5 Raines, K FDA Approves 6 in 1 Combo Vaccine for Babies The Vaccine Reaction Jan. 3, 2019
6 FDA. Recombivax-HB Package Insert. May 20, 2014
7 FDA. Engerix-B - Package Insert Apr. 28, 2016
8 FDA. TwinRix - Package Insert. Apr. 25, 2016
9 FDA. Pediarix Product Insert. Apr. 25,2016
10 FDA. HEPLISAV-B – Package Insert. Description.
11 FDA. HEPLISAV-B – Package Insert. Use In Specific Populations.
12 FDA. HEPLISAV-B – Package Insert. Use In Specific Populations.
13 FDA. VAXELIS – Package Insert Dec. 21, 2018
15 Raines, K FDA Approves 6 in 1 Combo Vaccine for Babies The Vaccine Reaction Jan. 3, 2019
16 CDC. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices MMWR. Jan. 12, 2018; 67(1);1–31
17 CDC. Viral Hepatitis – Hepatitis B FAQs for the public – Tests. May 23, 2016.