COMVAX- haemophilus influenzae type b capsular polysaccharide meningococcal outer membrane protein conjugate antigen and hepatitis b virus subtype adw hbsag surface protein antigen injection, suspension
Merck Sharp & Dohme Corp.
DESCRIPTION
COMVAX� [Haemophilus b Conjugate (Meningococcal Protein Conjugate) and Hepatitis B (Recombinant) Vaccine] is a sterile bivalent vaccine made of the antigenic components used in producing PedvaxHIB� [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] and RECOMBIVAX HB� [Hepatitis B Vaccine (Recombinant)]. These components are the Haemophilus influenzae type b capsular polysaccharide [polyribosylribitol phosphate (PRP)] that is covalently bound to an outer membrane protein complex (OMPC) of Neisseria meningitidis and hepatitis B surface antigen (HBsAg) from recombinant yeast cultures.
Haemophilus influenzae type b and Neisseria meningitidis serogroup B are grown in complex fermentation media. The primary ingredients of the phenol-inactivated fermentation medium for Haemophilus influenzae include an extract of yeast, nicotinamide adenine dinucleotide, hemin chloride, soy peptone, dextrose, and mineral salts and for Neisseria meningitidis include an extract of yeast, amino acids and mineral salts. The PRP is purified from the culture broth by purification procedures which include ethanol fractionation, enzyme digestion, phenol extraction and diafiltration. The OMPC from Neisseria meningitidis is purified by detergent extraction, ultracentrifugation, diafiltration and sterile filtration.
The PRP-OMPC conjugate is prepared by the chemical coupling of the highly purified PRP (polyribosylribitol phosphate) of Haemophilus influenzae type b (Haemophilus b, Ross strain) to an OMPC of the B11 strain of Neisseria meningitidis serogroup B. The coupling of the PRP to the OMPC is necessary for enhanced immunogenicity of the PRP. This coupling is confirmed by analysis of the components of the conjugate following chemical treatment which yields a unique amino acid. After conjugation, the aqueous bulk is then adsorbed onto an amorphous aluminum hydroxyphosphate sulfate adjuvant (previously referred to as aluminum hydroxide).
HBsAg is produced in recombinant 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 mechanical cell disruption and detergent extraction, and purified by a series of physical and chemical methods, which includes ion and hydrophobic chromatography, and diafiltration. 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, and 1% or less of the protein is of yeast origin.
The individual PRP-OMPC and HBsAg adjuvanted bulks are combined to produce COMVAX. Each 0.5 mL dose of COMVAX is formulated to contain 7.5 mcg PRP conjugated to approximately 125 mcg OMPC, 5 mcg HBsAg, approximately 225 mcg aluminum as amorphous aluminum hydroxyphosphate sulfate, and 35 mcg sodium borate (decahydrate) as a pH stabilizer, in 0.9% sodium chloride. The vaccine contains not more than 0.0004% (w/v) residual formaldehyde.
The potency of the PRP-OMPC component is measured by quantitating the polysaccharide concentration by an HPLC method. The potency of the HBsAg component is measured relative to a standard by an in vitro immunoassay.
The product contains no preservative.
COMVAX is a sterile suspension for intramuscular injection.
CLINICAL PHARMACOLOGY
Haemophilus influenzae type b Disease
Prior to the introduction of Haemophilus b conjugate vaccines, Haemophilus influenzae type b (Hib) was the most frequent cause of bacterial meningitis and a leading cause of serious, systemic bacterial disease in young children worldwide.{1-4}