RECOMBIVAX HB® HEPATITIS B VACCINE (RECOMBINANT)
DESCRIPTION
RECOMBIVAX HB* Hepatitis B Vaccine (Recombinant) is a non-infectious subunit viral vaccine derived from hepatitis B surface antigen (HBsAg) produced in yeast cells. A portion of the hepatitis B virus gene, coding for HBsAg, is cloned into yeast, and the vaccine for hepatitis B is produced from cultures of this recombinant yeast strain according to methods developed in the Merck Research Laboratories.
The antigen is harvested and purified from fermentation cultures of a recombinant strain of the yeast Saccharomyces cerevisiae containing the gene for the adw subtype of HBsAg. The 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 by a series of physical and chemical methods. The purified protein is treated in phosphate buffer with formaldehyde and then coprecipitated with alum (potassium aluminum sulfate) to form bulk vaccine adjuvanted with amorphous aluminum hydroxyphosphate sulfate. The vaccine contains no detectable yeast DNA but may contain not more than 1% yeast protein. The vaccine produced by the Merck method has been shown to be comparable to the plasma-derived vaccine in terms of animal potency (mouse, monkey, and chimpanzee) and protective efficacy (chimpanzee and human).
The vaccine against hepatitis B, prepared from recombinant yeast cultures, is free of association with human blood or blood products.
Each lot of hepatitis B vaccine is tested for safety, in mice and guinea pigs, and for sterility. RECOMBIVAX HB is a sterile suspension for intramuscular injection. However, for persons at risk of hemorrhage following intramuscular injection, the vaccine may be administered subcutaneously. (See DOSAGE AND ADMINISTRATION.) RECOMBIVAX HB Hepatitis B Vaccine (Recombinant) is supplied in three formulations. (See HOW SUPPLIED.)
Pediatric/Adolescent Formulation (With and Without Preservative), 10 mcg/mL: each 0.5 mL dose contains 5 mcg of hepatitis B surface antigen.
Adult Formulation (With and Without Preservative), 10 mcg/mL: each 1 mL dose contains 10 mcg of hepatitis B surface antigen.
Dialysis Formulation (With and Without Preservative), 40 mcg/mL: each 1 mL dose contains 40 mcg of hepatitis B surface antigen.
Formulations that contain a preservative include thimerosal, a mercury derivative, at 1:20,000 or 50 mcg/mL. All formulations contain approximately 0.5 mg of aluminum (provided as amorphous aluminum hydroxyphosphate sulfate, previously referred to as aluminum hydroxide) per mL of vaccine. In each formulation, hepatitis B surface antigen is adsorbed onto approximately 0.5 mg of aluminum (provided as amorphous aluminum hydroxyphosphate sulfate) per mL of vaccine. The vaccine is of the adw subtype. RECOMBIVAX HB is indicated for vaccination of persons at risk of infection from hepatitis B virus including all known subtypes. RECOMBIVAX HB Dialysis Formulation is indicated for vaccination of adult predialysis and dialysis patients against infection caused by all known subtypes of hepatitis B virus.
BL Fisher Note:
In 1991, the Centers for Disease Control and the American Academy of Pediatrics recommended that all 12 hour old newborns be injected with hepatitis B vaccine before leaving the hospital nursery and be given another dose of hepatitis B vaccine at 1 month and six months of age. At the time, NVIC protested this recommendation for the following reasons:
- little is known about the neurological and immunological status of a 12 hour old infant;
- hepatitis B is an adult disease occurring primarily in high risk populations such as IV drug users and persons with multiple sexual partners and the only way a newborn infant can contract hepatitis B is from aninfected mother or transfusion of infected blood;
- hepatitis B is not endemic in the US and less than 1/2 of one percent of mothers who give birth to babies in the US have hepatitis B disease; - the vaccine manufacturers admitted in their product manufacturer inserts that the long term protection offered by hepatitis B vaccine is unknown but that there are no detectable antibodies in the blood after 7 years
The result of the 1991 CDC and AAP hepatitis B vaccine recommendation was to expose American babies born between 1991 and 2000 to mercury preservatives in vaccines from the moment of birth. Mercury is a known neurotoxin and vaccine mercury preservatives have been associated with the development of autism and other neurodevelopmental disorders.
Now the study published in current issue of Pediatric Infectious Diseases Journal has found that injecting newborns with hepatitis B vaccine offers only five years of protection for most healthy infants.
Duration of Hepatitis B Immunity in Low Risk Children Receiving Hepatitis B Vaccinations from Birth
Kenneth M. Petersen, MD; Lisa R. Bulkow, MS; Brian J. McMahon, MD; Carolyn Zanis, BS; Marilyn Getty, RN; Helen Peters, RN; Alan J. Parkinson, PhD Pediatr Infect Dis J 23(7):650-655, 2004.
Abstract
Background: The duration of protection after hepatitis B vaccination of infants is unknown. Methods: We determined antibody to hepatitis B surface antigen (anti-HBs) at 4-13 years of age in 363 low risk children who had been vaccinated starting at birth with hepatitis B vaccine. Those with nonprotective titers (<10 mIU/mL) received a booster dose. We similarly followed 16 children of hepatitis B surface antigen (HBsAg)-positive mothers. Results: Of low risk infants receiving a plasma-derived vaccine, 41% (42 of 102) of those whose primary response was unknown and 24% (4 of 17) who had initially responded retained protective titers (>/=10 mIU/mL) of anti-HBs at 9 and 13 years, respectively. Of those who did not have protective antibody titers, 61% (33 of 54) and 67% (8 of 12), respectively, responded to a booster dose. In children of HBsAg-positive mothers, 31% retained protective anti-HBs at 12 years, and 90% (9 of 10) with nonprotective titers responded to a booster. In low risk children initially receiving a recombinant vaccine, 12.5% (26 of 208) and none (0 of 36) retained protective anti-HBs titers at 5 and 7 years of age, respectively. Of those who did not have protective titers, 90% (120 of 134) and 91% (32 of 35), respectively, responded to a booster.
Conclusions: Anti-HBs disappeared by 5 years of age in most children who were vaccinated with hepatitis B vaccine from birth. Although most children showed immunologic memory, one-third failed to demonstrate an anamnestic response to a booster dose. Additional long term studies of low risk infants are needed to determine duration of protection and the necessity for or timing of booster doses.
Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men
SC Hadler, DP Francis, JE Maynard, SE Thompson, FN Judson, DF Echenberg, DG
Ostrow, PM O'Malley, KA Penley, NL Altman, and et al.
Abstract
To study the duration of antibody persistence and protection provided by the hepatitis B vaccine, we followed 773 homosexual men for five years after completion of vaccination. Among the 635 participants in whom antibody levels above 9.9 sample ratio units (SRU) developed after vaccination, 15 percent lost antibody altogether, and in another 27 percent, antibody levels declined below 10 SRU within five years. The extent of the maximal antibody response strongly predicted the persistence of protective antibody. Hepatitis B infection occurred in 55 men; 8 of these infections were clinically important (characterized by the presence of the hepatitis B surface antigen and elevation of liver-enzyme levels), and two of the patients became hepatitis B virus carriers. The long-term risk of hepatitis B infection was inversely related to the maximal antibody response to vaccine. Most severe infections occurred among those who responded poorly or had no response to the vaccination. The risk of late infection with hepatitis B in those with an initially adequate vaccine response increased markedly when antibody levels decreased below 10 SRU, but only 1 of 34 late infections resulted in viremia and liver inflammation. A second series of vaccinations induced a moderate antibody response in 50 percent of the subjects who initially had no response or a poor response; however, the persistence of antibody was poor. Both antibody loss and the risk of severe disease should be considered when booster-dose strategies for the hepatitis B vaccine are being designed.
Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth.
Petersen KM, Bulkow LR, McMahon BJ, Zanis C, Getty M, Peters H, Parkinson AJ.
Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Alaska Native Tribal Health Consortium, Anchorage, AK 99508, USA.
BACKGROUND: The duration of protection after hepatitis B vaccination of infants is unknown. METHODS: We determined antibody to hepatitis B surface
antigen (anti-HBs) at 4-13 years of age in 363 low risk children who had been vaccinated starting at birth with hepatitis B vaccine. Those with nonprotective titers (<10 mIU/mL) received a booster dose. We similarly followed 16 children of hepatitis B surface antigen (HBsAg)-positive mothers. RESULTS: Of low risk infants receiving a plasma-derived vaccine, 41% (42 of 102) of those whose primary response was unknown and 24% (4 of 17) who had initially responded retained protective titers (> or = 10 mIU/mL) of anti-HBs at 9 and 13 years, respectively. Of those who did not have protective antibody titers, 61% (33 of 54) and 67% (8 of 12), respectively, responded to a booster dose. In children of HBsAg-positive mothers, 31% retained protective anti-HBs at 12 years, and 90% (9 of 10) with nonprotective titers responded to a booster. In low risk children initially receiving a recombinant vaccine, 12.5% (26 of 208) and
none (0 of 36) retained protective anti-HBs titers at 5 and 7 years of age,respectively. Of those who did not have protective titers, 90% (120 of 134) and 91% (32 of 35), respectively, responded to a booster.
CONCLUSIONS:
Anti-HBs disappeared by 5 years of age in most children who were vaccinated with hepatitis B vaccine from birth. Although most children showed immunologic memory, one-third failed to demonstrate an anamnestic response to a booster dose. Additional long term studies of low risk infants are needed to determine duration of protection and the necessity for or timing of booster doses.
PMID: 15247604 [PubMed - indexed for MEDLINE]
Mol Biol Rep. 2011 Jun 21. [Epub ahead of print]
In vivo study of hepatitis B vaccine effects on inflammation and metabolism gene expression.
Hamza H, Cao J, Li X, Zhao S.
SourceKey Lab of Animal Genetics, Breeding, and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
Abstract
Pharmaceutical companies usually perform safety testing of vaccines, but all requirements of the World Health Organization and drug pharmacopoeias depend on general toxicity testing, and the gene expression study of hepatitis B vaccine is not done routinely to test vaccine quality. In this study, we applied a new technique of gene expression analysis to detect the inflammation and metabolism genes that might be affected by hepatitis B vaccine in mouse liver. Mice were used and divided into three groups: the first and second groups were treated with one or two human doses of vaccine, respectively, and the third group was used as a control. A microarray test showed that expression of 144 genes in the liver was significantly changed after 1 day of vaccination. Seven of these genes, which were related to inflammation and metabolism, were chosen and confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) at 1, 4 and 7 days. The expression level of these genes can be considered as a biomarker for the effects of the vaccine.
PMID:21691704[PubMed - as supplied by publisher]
