title: Safety and immunogenicity of a recombinant hepatitis B vaccine manufactured by a modified process in renal pre-dialysis and dialysis patients.
abstract: BACKGROUND
  Patients with renal insufficiency are hyporesponsive to vaccination, including to hepatitis B vaccines. A manufacturing process modification for a hepatitis B vaccine (mpHBV) was studied in renal pre-dialysis and dialysis patients.
  
  
  METHODS
  This randomized, open-label, multicenter, estimation study enrolled previously unvaccinated, HBV-seronegative adult dialysis and pre-dialysis patients (N=276, median age 72.0 years). At 0, 1, 6, and 8 months, group 1 received a 1 mL intramuscular dose of mpHBV (containing 40 μg HBsAg) as a single injection, while group 2 received a 1 mL intramuscular dose of a licensed hepatitis B vaccine as two injections (each containing 20 μg HBsAg; 40 μg HBsAg total). Serum antibody to HBsAg (anti-HBs) was measured predose 1, and 1 month postdose 3 and 4. Anti-HBs geometric mean concentration (GMC) and seroprotection rate (SPR, % of subjects with anti-HBs titer ≥10 mIU/mL) were estimated at months 7 and 9.
  
  
  RESULTS
  For group 1, month 7 SPR was 48.5% (49/101, 95% CI: 38.4%, 58.7%); with an additional dose, month 9 SPR increased to 66.7% (66/99, 95% CI: 56.5%, 75.8%). For group 2, month 7 SPR was 57.7% (64/111, 95% CI: 47.9%, 67.0%); with an additional dose, month 9 SPR increased to 69.2% (72/104, 95% CI: 59.4%, 77.9%). group 1 GMCs at months 7 and 9 were 27.5 mIU/mL (95% CI: 15.7, 48.0) and 61.7 mIU/mL (95% CI: 34.2, 111.5), respectively. group 2 GMCs at months 7 and 9 were 48.7 mIU/mL (95% CI: 28.7, 82.7) and 115.8 mIU/mL (95% CI: 65.2, 205.5), respectively. There were 22 serious adverse events; none were considered related to study vaccine.
  
  
  CONCLUSIONS
  Both formulations were immunogenic in this population but required more vaccinations to reach seroprotective levels than comparable regimens in healthy individuals, as expected. The relatively reduced SPRs seen in this population support the need for routine screening and re-dosing in this population.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, United States. Electronic address: christopher_gilbert@merck.com.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Gilbert
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, United States.
authors.forename: Jon E
authors.initials: JE
authors.lastname: Stek
authors.affiliation: Fondazione "S. Maugeri" I.R.C.C.S. Medical Center, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villa
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, United States.
authors.forename: Stephanie O
authors.initials: SO
authors.lastname: Klopfer
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, United States.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Martin
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, United States.
authors.forename: Florian P
authors.initials: FP
authors.lastname: Schödel
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, United States.
authors.forename: Prakash K
authors.initials: PK
authors.lastname: Bhuyan
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation; D004311:Double-Blind Method; D005260:Female; 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 / Q000627:therapeutic use*; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic
keywords: Hepatitis B vaccine; Immunogenicity; Safety