quality issues dosages schedules

Hepatitis B vaccines:

Wolfgang JilgInstitute for Medical Microbiology and Hygiene

University of RegensburgRegensburg, Germany

Manufacturers of WHO “Prequalified” Hepatitis B Vaccines

VaccineHep B (recombinant)

Hep B (plasma-derived)

DPT-Hep B

DPT-Hep B-Hib

ManufacturerGlaxo/SKB (Belgium)Merck (USA)Green Cross (Korea)Lucky Goldstar (Korea)

Cheil Jedang (Korea)

Glaxo/SKB (Belgium)

Glaxo/SKB (Belgium)

Recombinant hepatitis B vaccinesin 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)

yeast (S)

yeast (S)

CHO (S+PreS2)

C127I (S+PreS2+ trunc. S1)

dosage (g)*childr. adol. adults

5 5 10

10 10 20

5 10 10

20 20 20

- - 20

* recom. schedules: month 0,1,6 (1)-(5); month 0,1,2,12 (1)-(4)

What should be expectedfrom an effective hepatitis B vaccine?

seroprotection rate (% individuals with anti-HBs 10 IU/L) 95 %

minimum requirements:

GMT > 500 IU/L

in healthy young adults (< 40 years), 1-2 months after booster dose

Influence of dosageon the immune response

Immune responses to different dosesof HB-vaccine (plasma-derived vaccine; Jilg et al 1988)

1

10

100

1000

10000

0 1 2 3 4 5 6 7 8 9 10 11 12

An

ti-H

Bs

IU

/l

(GM

T)

..

5 microgram (n= 25)10 microgram (n= 80)20 microgram (n=109)40 microgram (n= 20)

month after first vaccination

60

70

80

90

100

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

> 65

se

rop

rote

cti

on

ra

te (

%)

20 microgram/dose10 microgram/dose

age (years)

Vaccination against hepatitis B withRecombivax (10 g) or Engerix B (20 g)

(Averhoff et al, Am J Prev Med 1998; 15: 1)

Vaccination against hepatitis B withRecombivax (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/LGMT 2138 IU/L

individuals 40 years:seroprotection 81% 87%GMT 288 IU/L 1000 IU/L

Vaccination against hepatitis B withRecombivax 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

Influence of dosageon the immune response

higher dosage results in higher seroconversion rates and GMTs

correlation not linear

especially pronounced in elderly or immuno-suppressed

doses recommended by the manufacturer are sufficient

Influence of scheduleon the immune response

1

10

100

1000

10000

100000

0 1 2 3 4 5 6 7 8 9 10 11 12 13

An

ti-H

Bs

IU

/l

(GM

T)

..

group I: 0-1-6group II: 0-1-2-12group III: 0-1-12

month after first vaccination

vaccinations

53 IU/L

5846 IU/L 19912 IU/L

Vaccination against hepatitis B usingdifferent schedules (Jilg et al 1989)

11798 IU/L

1

10

100

1000

10000

0 1 2 3 4 5 6 7

An

ti-H

Bs

IU

/l

(GM

T)

..

group I: 0-1-6group II: 0-2-4group III: 0-6

Vaccination against hepatitis B usingdifferent schedules (Cassidy et al 2001)

month after first vaccination

2493 IU/L

1

10

100

1000

10000

0 1 2 3 4 5 6 7

An

ti-H

Bs

IU

/l

(GM

T)

..

group I: 0-1-6group II: 0-2-4group III: 0-6

Vaccination against hepatitis B usingdifferent schedules (Cassidy et al 2001)

month after first vaccination

2493 IU/L

675 IU/L

1

10

100

1000

10000

0 1 2 3 4 5 6 7

An

ti-H

Bs

IU

/l

(GM

T)

..

group I: 0-1-6group II: 0-2-4group III: 0-6

Vaccination against hepatitis B usingdifferent schedules (Cassidy et al 2001)

month after first vaccination

2493 IU/L

675 IU/L1136 IU/L

Influence of scheduleon 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

The End