What is Hepatitis B Vaccine?
There are six recombinant hepatitis B vaccines approved by the FDA in the U.S. Recombivax HB1; Engerix- B 2; Twinrix (combined with hepatitis A) 3; and Pediarix (combined with diphtheria and tetanus toxoids, acellular pertussis absorbed, and inactivated poliovirus) 4. The fifth vaccine, Comvax, 5 a Hepatitis B and Haemophilus B Conjugate (HIB) combination vaccine, was discontinued in 2014.6 The sixth is Heplisav-B, recombinant adjuvanted vaccine, and was recommended for use in adults by the CDC in 2018.7 The recombinant hepatitis B vaccine is created through genetic engineering of DNA by inserting a segment of the viral gene in a yeast cell,8 and the adjuvanted vaccine contains the addition CpG 1018 adjuvant, which had not been previously used in any vaccine licensed in the U.S.9
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.10
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.11
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.12
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).13
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.14
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.15
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. 16
The CDC recommends that all infants be vaccinated with three doses of hepatitis B vaccine beginning at 12 hours of age, with the last dose given before 18 months of age to prevent transmission by an infected mother to her newborn. 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.17
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. 18
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1 FDA. Recombivax-HB Package Insert. May 20, 2014
2 FDA. Engerix-B - Package Insert Apr. 28, 2016
3 FDA. TwinRix - Package Insert. Apr. 25, 2016
4 FDA. Pediarix Product Insert. Apr. 25,2016
5 FDA. Comvax Licensing Information. Apr. 20, 2011
6 Merck. Comvax Product Discontinuation Announcement. Mar. 31, 2014.
7 FDA. Vaccines, Blood & Biologics. Complete List of Vaccines Licensed for Immunization and Distribution in the U.S. Feb. 14, 2018.
8 CDC. Vaccines: The Pink Book. Principles of Vaccination. 13th Edition. 2015.
9 FDA. Hepatitis B Vaccine (Recombinant), Adjuvanted (HBV Surface Antigen (HBsAg) Protein with CpG 1018 adjuvant). Jul. 28. 2017
10 FDA. Recombivax-HB Package Insert. May 20, 2014
11 FDA. Engerix-B - Package Insert Apr. 28, 2016
12 FDA. TwinRix - Package Insert. Apr. 25, 2016
13 FDA. Pediarix Product Insert. Apr. 25,2016
14 FDA. HEPLISAV-B – Package Insert. Description.
15 FDA. HEPLISAV-B – Package Insert. Use In Specific Populations.
16 FDA. HEPLISAV-B – Package Insert. Use In Specific Populations.
17 CDC. Vaccine Recommendations of the ACIP - Hepatitis B ACIP Vaccine Recommendations. Revised Sept. 15, 2015
18 CDC. Viral Hepatitis – Hepatitis B FAQs for the public – Tests. May 23, 2016.