1. Hepatitis B vaccines: quality issues dosages schedules Wolfgang Jilg
Institute for Medical Microbiology and Hygiene
University of Regensburg
Regensburg, Germany

2. Manufacturers of WHO “Prequalified” Hepatitis B Vaccines
Hep B (recombinant)
Hep B (plasma-derived)
DPT-Hep B
DPT-Hep B-Hib
Manufacturer
Glaxo/SKB (Belgium)
Merck (USA)
Green Cross (Korea)
Lucky Goldstar (Korea)
Cheil Jedang (Korea)

3. Recombinant hepatitis B vaccines
in Europe
Product
(1) Recombivax (MSD)
(Gen-HB-Vax)
(2) Engerix B (GSK)
(3) Heprecomb Berna
(4) Genhevac B Pasteur
(5) Hepacare (Medeva)
source/
(antigen)
yeast (S)
CHO (S+PreS2)
C127I (S+PreS2
+ trunc. S1)
dosage (g)*
childr. adol. adults
5 5 10
* recom. schedules: month 0,1,6 (1)-(5); month 0,1,2,12 (1)-(4)

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

5. Influence of dosage
on the immune response

6. Immune responses to different doses
of HB-vaccine (plasma-derived vaccine; Jilg et al 1988)
month after first vaccination

7. Vaccination against hepatitis B with
Recombivax (10 g) or Engerix B (20 g)
(Averhoff et al, Am J Prev Med 1998; 15: 1)
age (years)

8. 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)
individuals <40 years:
92%
seroprotection
93%
1047 IU/L
GMT
2138 IU/L
individuals 40 years:
seroprotection
81%
87%
GMT
288 IU/L
1000 IU/L

9. Vaccination against hepatitis B with
Recombivax (10 g) or Engerix B (20 g)
(Rendi-Wagner et al, Vaccine 2001; 19: 2055)
Recombivax Engerix B
(n=256*) (n=155*)
seroprotection 79% 88%
GMT 142 IU/L 523 IU/L
* mean age of participants 43  15 (6 - 80) years

10. Vaccination against hepatitis B with
Recombivax or Engerix B: same dosage
(Bryan et al, Vaccine 1995; 13: 978)
Recombivax Engerix B
5 g doses (n=22/87):
seroprotection 98% 86%
GMT 570 IU/L 177 IU/L
10 g doses (n=46/91) :
seroprotection 100% 91%
GMT 744 IU/L 325 IU/L

11. 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

12. Influence of schedule
on the immune response

13. Vaccination against hepatitis B using
different schedules (Jilg et al 1989)
vaccinations
19912 IU/L
5846 IU/L
11798 IU/L
53 IU/L
month after first vaccination

14. Vaccination against hepatitis B using
different schedules (Cassidy et al 2001)
2493 IU/L
month after first vaccination

15. Vaccination against hepatitis B using
different schedules (Cassidy et al 2001)
2493 IU/L
675 IU/L
month after first vaccination

16. Vaccination against hepatitis B using
different schedules (Cassidy et al 2001)
2493 IU/L
1136 IU/L
675 IU/L
month after first vaccination

17. Accelerated schedule for hepatitis B immunization (Bock et al 1995)

18. 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

19. The End