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Hepatitis B vaccines:. quality issues dosages schedules. Wolfgang Jilg Institute for Medical Microbiology and Hygiene University of Regensburg Regensburg, Germany. Manufacturers of WHO “Prequalified” Hepatitis B Vaccines. Manufacturer Glaxo/SKB (Belgium) Merck (USA) Green Cross (Korea)
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Hepatitis B vaccines: • quality issues • dosages • schedules Wolfgang Jilg Institute for Medical Microbiology and Hygiene University of Regensburg Regensburg, Germany
Manufacturers of WHO “Prequalified” Hepatitis B Vaccines Manufacturer Glaxo/SKB (Belgium) Merck (USA) Green Cross (Korea) Lucky Goldstar (Korea) Cheil Jedang (Korea) Glaxo/SKB (Belgium) Glaxo/SKB (Belgium) Vaccine Hep B (recombinant) Hep B (plasma-derived) DPT-Hep B DPT-Hep B-Hib
Product (1) Recombivax (MSD) (Gen-HB-Vax) (2) Engerix B (GSK) (3) Heprecomb Berna (4) Genhevac B Pasteur (5) Hepacare (Medeva) Recombinant hepatitis B vaccines in Europe dosage (g)* childr. adol. adults 5 5 10 10 10 20 5 10 10 20 20 20 - - 20 source/ (antigen) yeast (S) yeast (S) yeast (S) CHO (S+PreS2) C127I (S+PreS2 + trunc. S1) * recom. schedules: month 0,1,6 (1)-(5); month 0,1,2,12 (1)-(4)
What should be expected from an effective hepatitis B vaccine? minimum requirements: • seroprotection rate (% individuals with anti-HBs 10 IU/L) 95 % • GMT > 500 IU/L in healthy young adults (< 40 years), 1-2 months after booster dose
Influence of dosage on the immune response
month after first vaccination Immune responses to different doses of HB-vaccine (plasma-derived vaccine; Jilg et al 1988)
age (years) Vaccination against hepatitis B with Recombivax (10 g) or Engerix B (20 g) (Averhoff et al, Am J Prev Med 1998; 15: 1)
Recombivax Engerix B (n=881) (n=873) 92% 93% seroprotection 2138 IU/L 1047 IU/L GMT 87% 81% seroprotection 288 IU/L 1000 IU/L GMT Vaccination against hepatitis B with Recombivax (10 g) or Engerix B (20 g) (Averhoff et al, Am J Prev Med 1998; 15: 1) individuals <40 years: individuals 40 years:
Recombivax Engerix B Vaccination against hepatitis B with Recombivax or Engerix B: same dosage (Bryan et al, Vaccine 1995; 13: 978) 5 g doses (n=22/87): seroprotection98% 86% GMT570 IU/L 177 IU/L 10 g doses (n=46/91) : seroprotection100% 91% GMT744 IU/L 325 IU/L
Influence of dosage on the immune response • higher dosage results in higher seroconversion rates and GMTs • doses recommended by the manufacturer are sufficient • correlation not linear • especially pronounced in elderly or immuno- suppressed
Influence of schedule on the immune response
19912 IU/L 5846 IU/L 11798 IU/L 53 IU/L Vaccination against hepatitis B using different schedules (Jilg et al 1989) vaccinations month after first vaccination
2493 IU/L Vaccination against hepatitis B using different schedules (Cassidy et al 2001) month after first vaccination
2493 IU/L 675 IU/L Vaccination against hepatitis B using different schedules (Cassidy et al 2001) month after first vaccination
2493 IU/L 1136 IU/L Vaccination against hepatitis B using different schedules (Cassidy et al 2001) 675 IU/L month after first vaccination
Influence of schedule on the immune response • immune responses increase with increasing interval between the first and third dose • additional dose at month 2 increases early but not final immune response when booster dose is given at month 12 • minor delays in giving the 2nd or 3rd dose are un- likely to have a negative impact on vaccine response