• Vaccine Name: PedvaxHIB
• Target Pathogen: Haemophilus influenzae
• Target Disease: Meningitis
• Product Name: Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)
• Tradename: PedvaxHIB
• Manufacturer: Merck & Co, Inc.
• Vaccine Ontology ID: VO_0000083
• CDC CVX code: 49
• Type: Conjugate vaccine
• Status: Licensed
• Location Licensed: USA
• Host Species for Licensed Use: Human
• Antigen: Haemophilus b capsular polyribosyl-ribitol-phosphate( PRP)-Neisseria meningitidis outer membrane protein complex (OMPC)
• Adjuvant:
  • Adjuvant name:
  • VO adjuvant ID: VO_0000127
  • Description: PedvaxHIB is a highly purified capsular polysaccharide (polyribosylribitol phosphate or PRP) of Haemophilus influenzae type b (Haemophilus b, Ross strain) that is covalently bound to an outer membrane protein complex (OMPC) of the B11 strain of Neisseria meningitidis serogroup B. The covalent bonding of the PRP to the OMPC which is necessary for enhanced immunogenicity of the PRP is confirmed by quantitative analysis of the conjugate’s components following chemical treatment which yields a unique amino acid
• Preparation: Haemophilus influenzae type b and Neisseria meningitidis serogroup B are grown in complex fermentation media. The PRP is purified from the culture broth by purification procedures which include ethanol ractionation, enzyme digestion, phenol extraction and diafiltration. The OMPC from Neisseria meningitidis is purified by detergent extraction, ultracentrifugation, diafiltration and sterile filtration (PedvasHIB).
• Immunization Route: Intramuscular injection (i.m.)
• Virulence: No virulence
• Storage: Store vaccine at 2-8°C (36-46°F).
• Approved Age for Licensed Use: Infants and children 2 to 71 months of age (PedvasHIB).
• Contraindication: Hypersensitivity to any component of the vaccine or the diluent or persons who develop symptoms suggestive of hypersensitivity after an injection should not receive further injections of the vaccine.
• Description: PedvaxHIB is a highly purified capsular polysaccharide (polyribosylribitol phosphate or PRP) of Haemophilus influenzae type b (Haemophilus b, Ross strain) that is covalently bound to an outer membrane protein complex (OMPC) of the B11 strain of Neisseria meningitidis serogroup B. The covalent bonding of the PRP to the OMPC which is necessary for enhanced immunogenicity of the PRP is confirmed by quantitative analysis of the conjugate’s components following chemical treatment which yields a unique amino acid (PedvasHIB).
  
  Nonconjugated PRP vaccines are capable of stimulating B-lymphocytes to produce antibody without the help of T-lymphocytes (T-independent). The responses to many other antigens are augmented by helper T-lymphocytes (T-dependent). PedvaxHIB is a PRP-conjugate vaccine in which the PRP is covalently bound to the OMPC carrier29 producing an antigen which is postulated to convert the T-independent antigen (PRP alone) into a T-dependent antigen resulting in both an enhanced antibody response and immunologic memory (Marburg 1986).

Human Response

• Vaccination Protocol: Liquid PedvaxHIB is indicated for routine vaccination against invasive disease caused by Haemophilus influenzae type b in infants and children 2 to 71 months of age. Liquid PedvaxHIB is ready to use and does not require a diluent. Each 0.5 mL dose of Liquid PedvaxHIB is a sterile product formulated to contain: 7.5 mcg of Haemophilus b PRP, 125 mcg of Neisseria meningitidis OMPC and 225 mcg of aluminum as amorphous aluminum hydroxyphosphate sulfate (previously referred to as aluminum hydroxide), in 0.9% sodium chloride, but does not contain lactose or thimerosal.
  
  Infants 2 to 14 months of age should receive a 0.5 mL dose of vaccine ideally beginning at 2 months of age followed by a 0.5 mL dose 2 months later (or as soon as possible thereafter). When the primary two-dose regimen is completed before 12 months of age, a booster dose is required . Infants born prematurely, regardless of birth weight, should be vaccinated at the same chronological age and according to the same schedule and precautions as full-term infants and children.
  
  Children 15 months of age and older previously unvaccinated against Hib disease should receive a single 0.5 mL dose of vaccine.
  
  In infants completing the primary two-dose regimen before 12 months of age, a booster dose (0.5 mL) should be administered at 12 to 15 months of age, but not earlier than 2 months after the second dose (PedvasHIB).
• Persistence: A booster dose of PedvaxHIB is required in infants who complete the primary two-dose regimen before 12 months of age. This booster dose will help maintain antibody levels during the first two years of life when children are at highest risk for invasive Hib disease.
• Side Effects: The most frequently reported (>1%) adverse reactions, in decreasing order of frequency, were irritability, sleepiness, injection site pain/soreness, injection site erythema (≤2.5 cm diameter), injection site swelling/induration, unusual high-pitched crying, prolonged crying (>4 hr), diarrhea, vomiting, crying, pain, otitis media, rash, and upper respiratory infection (PedvasHIB).
  
  The use of Haemophilus b Polysaccharide Vaccines and another Haemophilus b Conjugate Vaccine has been associated with the following additional adverse effects: early onset Hib disease and Guillain-Barré syndrome (Meekison et al., 1989).
• Efficacy: PedvaxHIB was initially evaluated in 3,486 Native American (Navajo) infants, who completed the primary two-dose regimen in a randomized, double-blind, placebo-controlled study (The Protective Efficacy Study). Each infant in this study received two doses of either placebo or lyophilized PedvaxHIB with the first dose administered at a mean of 8 weeks of age and the second administered approximately two months later. Following the primary two-dose regimen, the protective efficacy of lyophilized PedvaxHIB was calculated to be 93% with a 95% confidence interval of 57%-98% (p=0.001, twotailed).All original participants were then followed two years and nine months from termination of the study. Efficacy for this follow-up period, estimated from persondays at risk, was 96.6% (95 C.I., 72.2-99.9%) in children under 18 months of age and 100% (95 C.I., 23.5-100%) in children over 18 months of age (PedvasHIB).
  
  Lyophilized PedvaxHIB induced antibody levels greater than 1.0 mcg/mL in children who were poor responders to nonconjugated PRP vaccines (PedvasHIB). In addition, lyophilized PedvaxHIB has been studied in children at high risk of Hib disease because of genetically-related deficiencies [Blacks who were Km(1) allotype negative and Caucasians who were G2m(23) allotype negative] and are considered hyporesponsive to nonconjugated PRP vaccines on this basis. The hyporesponsive children had anti-PRP responses comparable to those of allotype positive children of similar age range when vaccinated
  with lyophilized PedvaxHIB. All children achieved anti-PRP levels of >1.0 mcg/mL (PedvasHIB).