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What is Hib Vaccine?

History of Hib vaccine

The Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccine has been available in the U.S. since December 1987. Conjugation is the process of chemically bonding a polysaccharide to a protein “carrier” to increase the effectiveness of the polysaccharide antigen.1 Two conjugate Hib vaccines are licensed for use in the U.S. for infants as young as 6 weeks old. A third is approved only for the last dose of Hib among children ages 12 months and older.

Three combination vaccines that contain Hib conjugate vaccine are also available, for a total of six vaccines containing Haemophilis B that are licensed for vaccination and distribution in the U.S. One of the three combination vaccines was only approved by the FDA on June 14, 2012, a Meningococcal Groups C and Y and Haemophilus b tetanus toxoid conjugate vaccine for infants and children ages 6 weeks through 18 months.2,3

The six vaccines are: Sanofi Pasteur’s ActHIB, which is a conjugate vaccine containing Haemophilus b and meningococcal protein conjugate; GlaxoSmithKline Biologicals’ Hiberix, which is a tetanus toxoid and Haemophilus b conjugate vaccine; Merck, Sharpe & Dohm’s PedvaxHIB, which is a meningococcal protein and Haemophilus b conjugate; Merck & Co.’s Comvax, which contains Haemophilus b conjugate, meningococcal protein conjugate and hepatitis B vaccine (recombinant); Sanofi Pasteur’s Pentacel, which consists of diphtheria and tetanus toxoids, acellular pertussis adsorbed, inactivated poliovirus, and Haemophilus b conjugate (tetanus toxoid conjugate); and GlaxoSmithKline’s MenHibrix, which consists of meningococcal groups C and Y and Haemophilus b tetanus toxoid conjugate.

None of the Hib vaccines protect against any other types of Haemophilus infection than type b. It also does not protect against meningitis caused by any other bacteria. It is not known whether Hib vaccine protects against ear infections.4

The Advisory Committee on Immunization Practices (ACIP) has approved the Hib vaccine for use with children at 2, 4, 6 and 12-15 months of age. The new vaccine, MenHibrix, has been approved for children ages 6 weeks through 18 months. Depending on which brand of Hib is used, some children may not need the dose at 6 months. Although generally speaking children over age 5 years old do not need the Hib vaccine, sometimes it is given those children and even adults with special health conditions such as those with sickle cell disease, or HIV/AIDS, or those who have had their spleens removed, had a bone marrow transplant or have cancer treatments with drugs.5,6

  • ActHIB is a conjugate vaccine made by Sanofi Pasteur that is indicated for vaccinated infants and children ages 2 months through 18 months for the prevention of H. influenzae type b and/or diphtheria, tetanus and pertussis.7 The protein carrier is tetanus toxoid.8 It is a lyophilized powder that is reconstituted at the time of use with either saline (0.4% sodium chloride) or with Sanofi’s Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (whole-cell pertussis vaccine DTP) or with Tripedia, Sanofi Pasteur’s Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTap) (when reconstituted known as TriHIBit).

    ActHIB is injected into the muscle. According to the manufacturer’s product insert, the vaccine consists of Haemophilus b capsular polysaccharide (polyribosyl-ribitol-phosphate, PRP), a high molecular weight polymer prepared from the Haemophilus influenzae type b strain 1482 grown in a semi-synthetic medium covalently bound to tetanus toxoid. The tetanus toxoid is prepared by extraction, ammonium sulfate purification, and formalin inactivation of the toxin from cultures of Clostridium tetani (Harvard strain) grown in a modified Mueller and Miller medium. Further manufacturing steps reduce residual formaldehyde levels.

    According to the manufacturer, when ActHIB is reconstituted with saline, each dose is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to 24 mcg of inactivated tetanus toxoid and 8.5% of sucrose. When it is combined with Sanofi’s DTP vaccine, each dose is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to 24 mcg of inactivated tetanus toxoid, 8.5% of sucrose, 6.7 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid, and an estimate of 4 protective units of pertussis vaccine. Thimerosal is added as a preservative to the DTP vaccine.

    When Act HIB is combined with Tripedia (TrHIBit) by reconstitution for booster dose, each dose is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to 24 mcg of inactivated tetanus toxoid, 8.5% of sucrose, 6.7 Lf of diphtheria toxoid, 5 Lf of tetanus toxoid and 46.8 mcg of pertussis antigens. Tripedia is formulated without preservatives, but contains a trace amount of thimerosal from the manufacturing process.
  • Hiberix is a conjugate vaccine made by GlaxoSmithKline that is indicated for vaccination as a booster dose for use in children ages 15 months through 4 years of age, prior to the fifth birthday, for the prevention of Haemophilus type b.9 The protein carrier is tetanus toxoid. It is a lyophilized vaccine that is reconstituted with saline and then injected into the muscle. According to the manufacturer’s product insert, Hiberix contains Haemophilus b capsular polysaccharide (polyribosyl-ribitol-phosphate), a high molecular weight polymer prepared from the Haemophilus influenzae type b strain 20,752 grown in a synthetic medium. The tetanus toxin in the vaccine is prepared from Clostridium tetani grown in a semi-synthetic medium, and detoxified with formaldehyde. The polysaccharide is covalently bound to the tetanus toxoid.

    Once it’s reconstituted, each dose of Hiberix is formulated to contain 10 mcg of purified capsular polysaccharide conjugated to approximately 25 mcg of tetanus toxoid, 12.6 mg of lactose, and less than or equal to 0.5 mcg of residual formaldehyde. It does not contain preservatives or latex.
  • PedvaxHIB, is a conjugate vaccine manufactured by Merck & Co. that is indicated for vaccination against Haemophilus influennzae type b in infants and children ages 2 to 71 months of age.10 It is a liquid conjugate vaccine with meningococcal group B outer membrane as the protein carrier. It does not need to be reconstituted, and is injected into the muscle. It is a purified polysaccharide (polyribosylribitol phosphate or PRP) of Haemophilus influenzae type b (Haemophilus b, Ross strain) covalently bound to an outer membrane protein complex of the B11 strain of Neisseria meningitides serogroup B. The covalent bonding is necessary for enhanced immunogenicity.

    Each dose of Liquid PedvaxHIB is formulated to contain 7.5 mcg of Haemophilus b PRP, 125 mcg of Neisseria meningitides OMPC and 225 mcg of aluminum as amorphous aluminum hydroxyphosphate sulfate (previously referred to as aluminum hydroxide), in 0.9 percent sodium chloride. It does not contain lactose or thimerosal.
  • Comvax is manufactured by Merck & co., and is indicated for vaccination against Haemophilus influenzae type b and against infection caused by all known subtypes of hepatitis B in infants 6 weeks to 15 months of age born to HBsAg-negative mothers.11 According to the manufacturer’s product insert vaccination with Comvax should begin at approximately 2 months of age or as soon thereafter as possible, and no later than 10 months of age. It is administered on a 3-dose schedule; however, infants who do not receive a PRP-OMPC-containing product (PedvaxHIB, Comvax) until 11 months of age do not require three doses, even though three doses of an HBsAg-containing product are required for complete vaccination against hepatitis B regardless of age.
  • Pentacel is manufactured by Sanofi Pasteur and is indicated for vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b in children ages 6 weeks through 4 years of age and prior to the fifth birthday.12 It is injected into the muscle in a 4-dose schedule. The antigenic forms in the vaccine include a mixture of two toxoids with five acellular pertussis antigens, three types of poliovirus, and Hib conjugated to tetanus toxoid.13 Specifically, according to the manufacturer’s product insert14, each dose of Pentacel contains 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 (40 D-angigen units DU Type 1 Mahoney, 8 DU Type 2 MEF-1, 32 DU Type 3 Saukett) and 10 mcg PRP of Haemophilus influenzae type b.

    Other ingredients in each dose of Pentacel include 1.5 mg aluminum phosphate (0.33 mg aluminum) as the adjuvant, polysorbate 80 (approximately 10 ppm), less than or equal to 5 mcg residual formaldehyde, less than 50 ng residual glutaraldehyde, less than 50 ng residual bovine serum albumin, 3.3 mg (0.6% v/v) 2-phenoxyethanol (not as preservative), less than 4 pg of neomycin and less than 4 pg polymyxin B sulfate.

    The Cornyebacterium diphtheria is grown in modified Mueller’s growth medium and purified by ammonium sulfate fractionation. The diphtheria toxin is detoxified with formaldehyde and diafiltered. Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. The tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration. The diphtheria and tetanus toxoids are individually adsorbed onto aluminum phosphate. The acellular pertussis antigens are produced from Bordetella pertussis cultures grown in Stainer-Scholte medium and modified by the addition of casamino acids and dimethyl-beta-cyclodextrin. PT, FHA, and PRN are isolated separately from the supernatant culture medium. FIM are extracted and copurified from the bacterial cells. The pertussis antigens are purified by sequential filtration, salt precipitation ultrafiltration and chromoatography. PT is detoxified with glutaraldehyde. FHA is treated with formaldhyde and the residual aldehydes are removed by ultrafiltration. The individual antigens are adsorbed separately onto aluminum phosphate.

    According to the manufacturer’s product insert, poliovirus Types 1, 2, and 3 are each grown in separate cultures of MRC-5 cells (a line of human diploid cells obtained from the normal lung tissue of a 14-week-old male fetus15). The cells are grown in CMRL 1969 medium supplemented with calf serum. After clarification and filtration, the viral suspensions are concentrated by ultrafiltration and purified by liquid chromatography. The viral suspensions are inactivated with formaldehyde. The monovalents are then combined to produce the trivalent poliovirus concentrate.

    The adsorbed diphtheria, tetanus and acellular pertussis antigens are combined with aluminum phosphate as an adjuvant, 2-phenoxyethanol (not preservative) and water for injection. The trivalent poliovirus concentrate is then added and the DTaP-IPV component is diluted to its final concentration. The DTaP-IPV component does not contain preservative.

    Also according to the manufacturer, Pentacel contains the same pertussis antigens as another vaccine, Daptacel, and is manufactured by the same process as Daptacel; however, Pentacel vaccine contains twice as much detoxified PT and four times as much FHA as Daptacel.
  • MenHibrix is manufactured by GlaxoSmithKline and was approved by the FDA on June 14, 2012 for vaccination against Neisseria meningitides serogroups C and Y and Haemophilus influenzae be for children ages 6 weeks through 18 months old. It is injected into the muscle in a 4-dose schedule.16 MenHibrix is reconstituted with a saline dilutent. According to the manufacturer’s product insert, MenHibrix contains Neisseria meningitides serogroup C and Y capsular polysaccharide antigens and Haemophilus b capsular polysaccharide (polyribosyl-ribitol-phosphate — PRP). The Neisseria meningitides C strain and Y strain are grown in a synthetic medium.

The tetanus toxin is prepared from Clostridium tetani grown in a semi-synthetic medium and detoxified with formaldehyde. Each capsular polysaccharide is individually covalently bound to the inactivated tetanus toxoid. After purification the conjugate is lyophilized in the presence of sucrose as a stabilizer. When reconstituted each dose of MenHibrix is formulated to contain 5 mcg of purified Neisseria meningitidis C capsular polysaccharide conjugated to approximately 5 mcg of tetanus toxoid, and 2.5 mcg of purified Haemophilus b capsular polysaccharide conjugated to approximately 6.25 mcg of tetanus toxoid. Each dose also conatins 96.8 mcg of trometamol-HCI, 12.6 mg of sucrose, and about 0.72 mcg of residual formaldehyde. This vaccine does not contain preservatives.

IMPORTANT NOTE: NVIC encourages you to become fully informed about Haemophilus Influenza Type B (Hib) and the Hib 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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References

1 CDC.gov. Haemophilus Influenzae Type B. The Pink Book. No Date. Online. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/hib.pdf. (Accessed June 2012)

2 FDA.gov. Complete List of Vaccines Licensed for Immunization and Distribution in the U.S. Vaccines, Blood & Biologics. April 19, 2012. Online. (Accessed June 2012)

3 FDA.gov. FDA Approves New Combination Vaccine that Protects Children Against Two Bacterial Diseases. FDA News & Events. June 14, 2012. Online. (Accessed June 2012)

4 Todar K. Todar’s Online Textbook of Bacteriology. Haemophilus influenzae and Hib meningitis. 2008-2012. Online. (Accessed June 2012)

5 CDC.gov. Haemophilus Influenzae Type b (Hib) Vaccine. Vaccine Information Sheet. Dec. 16, 1998. Online. http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-hib.pdf. (Accessed June 2012)

6 FDA.gov. FDA Approves New Combination Vaccine that Protects Children Against Two Bacterial Diseases. FDA News & Events. June 14, 2012. Online. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm308350.htm. (Accessed June 2012)

7 FDA.gov. ActHIB. Vaccines, Blood & Biologics. Aug. 18, 2011. Online. (Accessed June 2012)

8 FDA.gov. Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) ActHIB manufacturer’s product insert. May 6, 2009. Online. (Accessed June 20012)

9 FDA.gov. Hiberix Manufacturer’s Product Insert. No date. Online. (Accessed June 2012)

10 FDA.gov. PedvaxHIB Manufacturer’s Product Insert. 1998. Online. (Accessed June 2012)

11 FDA.gov. Comvax Manufacturer’s Product Insert. 2001. Online. (Accessed June 2012)

12 FDA.gov. Pentacel Manufacturer’s Product Insert. July 2011. Online. (Accessed June 2012)

13 Grabenstein JD. ImmunoFacts: Vaccines and Immunologic Drugs. Diphtheria & Tetanus Toxoids with Acellular Pertussis Adsorbed, Inactivated Poliovirus, and Haemophilus Influenzae Type b Conjugate Vaccine. 2011. pp 78-87.

14 FDA.gov. Pentacel Manufacturer’s Product Insert. July 2011. Online. (Accessed June 2012)

15 ViroMed.com. Selected Profiles of Cell Cultures―MRC-5. ViroMed Laboratories. No date. Online. (Accessed June 2012)

16 FDA.gov. Menhibrix Manufacturer’s Product Insert. June 2012. Online.. (Accessed June 2012)


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