title: Immunogenicity and safety of a Haemophilus influenzae B (Hib)-hepatitis B vaccine with a modified process hepatitis B component administered with concomitant pneumococcal conjugate vaccine to infants.
abstract: BACKGROUND
  A hepatitis B vaccine was manufactured with a modified process (mpHBV) that incorporated double the usual amount of phosphate. Following a study in young adults, the mpHBV was evaluated in infants in a combination hepatitis B and Haemophilus influenzae B vaccine (mpHBV-Hib).
  
  
  METHODS
  The mpHBV-Hib was compared with the licensed bivalent HBV-Hib vaccine Comvax™ for immunogenicity and safety. Both vaccines contained 5 μg/0.5 mL of hepatitis B surface antigen (HBsAg) and 7.5 μg/0.5 mL of PRP-OMPC (polyribosylribitol phosphate outer membrane protein complex). A total of 543 infants were randomized 1:1 to receive either vaccine at 2, 4 and 12 months of age. A pneumococcal conjugate vaccine (PCV) was given concomitantly. Immunogenicity was assessed at 1-month post-dose 3.
  
  
  RESULTS
  Seroprotection rates [% subjects with anti-hepatitis B surface antigen antibody titers (anti-HBs) ≥10 mIU/mL)] were 100% and 99% for mpHBV-Hib and the licensed control (Comvax™), respectively. Anti-HBs geometric mean titers (GMTs) were 4204 (95% CI, 3411-5182) and 1683 (95% CI, 1350-2099) mIU/mL, respectively. Anti-PRP seroprotection rates (SPR) at ≥0.15 μg/mL and at ≥1.0 μg/mL were 97% and 94%, respectively, for mpHBV-Hib and 96% and 92%, respectively, for the control. Anti-PRP GMTs were 7.1 μg/mL for mpHBV-Hib and 8.0 μg/mL for the control. Reactogenicity of the two vaccines was similar.
  
  
  CONCLUSIONS
  The mpHBV in combination with Hib and with co-administered PCV was highly immunogenic. The safety profile of mpHBV-Hib was comparable to the licensed control. Both the control and mpHBV-Hib met acceptability criteria for seroprotection rates to hepatitis B, with higher anti-HBs GMTs noted for mpHBV-Hib.
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA. andrew_wen-tseng_lee@merck.com
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lee
authors.forename: Timo
authors.initials: T
authors.lastname: Vesikari
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Gilbert
authors.forename: Stephanie O
authors.initials: SO
authors.lastname: Klopfer
authors.forename: Florian P
authors.initials: FP
authors.lastname: Schödel
authors.forename: Prakash K
authors.initials: PK
authors.lastname: Bhuyan
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D006509:Hepatitis B / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D007223:Infant; D008297:Male; D022242:Pneumococcal Vaccines / Q000008:administration & dosage; D011135:Polysaccharides, Bacterial / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; C104289:COMVAX; D018073:Haemophilus Vaccines; C061964:Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate