Imunização ativa contra o virus da Hepatite B com baixas doses da vacina plasma derivada por via intradérmica

Rev. Inst. Med. trop. São Paulo

31 {2): 91-94, março-abril, 1989

ACTIVE IMMUNIZATION AGAINST HEPATITIS B VIRUS (HBV) WITH LOW-DOSES OF

PLASMA-DERIVED VACCINE BY INTRADERMAL ROUTE

F l a i r J o s é C A R R I L H O (1), M a r i a L ú c i a Q U E I R O Z (2), L u i z C a e t a n o d a S I L V A (1), L u í s E d m u n d o P i n t o d a F O N S E C A (1), C e l s o G R A N A T O ( 3 ) , I s a b e l O B A (3) & L e d a O B A R A (4)

S U M M A R Y

S c h e d u l e for v a c c i n a t i o n a g a i n s t H B V infection has u s u a l l y been based on three

separate injections of 20 meg of the v a c c i n e by i n t r a m u s c u l a r route. O n e of the

m a i n shortcomings to its use in large scale programs has been its h i g h cost. Ninety

out of 300 health workers were s u b m i t t e d to three injections of 2 m c g of p l a s m a

-derived v a c c i n e ( P D V ) by intradermal ( I D ) route on d a y s 0, 30, a n d 180. A n t i - H B s

was detected in 74 (82.2%) after the second dose and in 80 (88.9%) after the third

dose, a non-significant difference. However, levels above 10 times the cut-off were

observed in 29 (32.2%) and 77 (85.5%), respectively (p < 0.001). T h e results showed

that a low-dose schedule is effective when used in health workers and should be

tried with other risk groups.

K E Y W O R D S : H e p a t i t i s B ; H e p a t i t i s B v i r u s ; H e p a t i t i s B vaccine; I m m u n i z a t i o n .

I N T R O D U C T I O N

P l a s m a - d e r i v e d v a c c i n e is v e r y effective

against H B V

1 3 4 8

'

1 5

. T h e protective antibody

against surface antigen ( a n t i - H B s ) develops

af-ter three doses of the v a c c i n e in more t h a n 90%

of the g e n e r a l p o p u l a t i o n

3

. T h e r e c o m e n d e d

schedule in most p r o g r a m s of active i m m u n i

-zation has been three separate injections of 20

meg per dose by i n t r a m u s c u l a r (IM) route in

del-toid region3 4 7 1 5

. One of the m a i n difficulties

to apply this p r o g r a m in underdeveloped

coun-tries is its h i g h cost. F o r this reason different

schedules with lower doses have been tried, s u c h

as 10, 5 and 2.5 meg by i n t r a m u s c u l a r routes2

7. i2, i3 More recently, 2 meg by intradermal ( I D )

route was employed, w i t h p r o m i s i n g results5 8

9, io, i3 However, the samples in most studies were

rather s m a l l .

T h e aim of this s t u d y was to investigate the

efficacy of the plasma-derived vaccine by u s i n g

2 meg by I D route.

M A T E R I A L A N D M E T H O D S

A total of 300 hospital health workers were

submitted to a serological study of H B V mar

(1) C l i n i c a l H e p a t o l o g y B r a n c h , D e p a r t m e n t o f G a s t r o e n t e r o l o g y , F a c u l d a d e d e M e d i c i n a d a U n i v e r s i d a d e d e S ã o P a u l o . S ã o P a u l o , S P , B r a z i l . (2) H o s p i t a l O s v a l d o C r u z . S ã o P a u l o , S P , B r a z i l . (3) H e p a t i t i s B r a n c h , D i v i s i o n o f V i r o l o g y , I n s t i t u t o A d o l f o L u t z . S ã o P a u l o , S P , B r a z i l . (4) B I E S P , I n s t i t u t o P a u l i s t a d e P a t o l o g i a C l í n i c a . S ã o P a u l o , S P , B r a z i l . A d d r e s s f o r c o r r e s p o n d e n c e : D r . F l a i r J o s é C a r r i l h o . C l i n i c a l H e p a t o l o g y B r a n c h , D e p a r t m e n t o f G a s t r o e n t e r o l o g y , F a c u l d a d e d e M e d i c i n a d a U n i v e r s i d a d e d e S ã o P a u l o . A v . D r . A r n a l d o , 4 5 5 . C E P 01246 S ã o P a u l o , S P , B r a z i l .

kers. H e p a t i t i s B surface antigen ( H B s A g ) and

its antibody ( a n t i - H B s ) a n d total core antibody

( a n t i - H B c ) were studied by using an enzyme-lin­

ked i m m u n o a s s a y ( A U S Z Y M E I I , A U S A B E I A

and C O R Z Y M E , respectively, produced by A B ­

B O T T L A B O R A T O R I E S , U. S . A . ) . T h e sche­

dule of active i m m u n i z a t i o n was similar to that

used by M I L L E R et a l

1 1

: one dose at d a y zero,

and subsequent doses at one and s i x - m o n t h in­

tervals u s i n g 2 meg by I D route. O n l y workers

without H B V m a r k e r s were s u b m i t t e d to v a c c i ­

nation on a voluntary basis.

Seroconversion to a n t i - H B s was studied im­

mediately before and one m o n t h after the third

dose. A rough s e m i q u a n t i t a t i v e determination

was based on the value of the cut-off. I t was con­

sidered a good antibody response when the value

obtained was above then times the cut-off level

8

.

I n the screening of the 300 workers, a n t i - H B c

was detected i n 43 (14.3%), i n c l u d i n g 9 (3.0%)

with H B s A g and 34 (11.3%) of a n t i - H B s ( F i g u r e

1). O n l y 90 (35.0%) out of 257 workers without

H B V m a r k e r s accepted the v a c c i n a t i o n schedu­

le. T h i s group c o n s i s t e d of 68 females a n d 22

males; w i t h a m e a n age of 37.4 ± 8.4 years (22

- 56 years).

R E S U L T S

T h e results showed that, a n t i - H B s was de

tected i n 74 (82.2%

c

) and 80 (88.9%) workers, res­

pectively before and after the third dose, a non­

significant difference (chi-square = 1.1238, 0.30

> p > 0.20, F i g u r e 2). However, a good antibody

response was obtained in only 29 out of 90 (32.2% )

after the second dose a n d in 77 out of 90 (85.5%)

w o r k e r s a f t e r t h e t h i r d d o s e ( c h i - s q u a r e =

50.6909, p < 0.001), as shown in F i g u r e 3.

D I S C U S S I O N

O u r results clearly show t h a t v a c c i n a t i o n

w i t h three doses of 2 meg of H B V plasma-derived

by I D route produces a h i g h number of serocon­

version to a n t i - H B s (88.9%). T h e s e results agree

w i t h those p u b l i s h e d by M I L L E R et a l

1 1

a n d

R E D F I E L D et a l

1 4

. T o our knowledge only few

papers based on s u c h a schedule of i m m u n i z a ­

tion have been published to d a t e

5 9 1 0 1 1 1 4 1 6

.

I t is worth m e n t i o n i n g that the seroconversion

TOTAL A N T I - H B c

( n « 3 0 0 )

Y E S NO 9 0 ( 3 5 . 0 % ) 167(65.0%) F i g . 1 - - F r e q u e n c y o f H B V m a r k e r s i n a s c r e e n i n g o f 300 h o s p i t a l h e a l t h w o r k e r s . [ ] < I O x s CUT-OFF A F T E R T H E A F T E R T H E 2nd D O S E 3 r d D O S E

X

2

- 5 0 . 6 9 0 9 , p < 0 . 0 0 1

F i g . 2 — A n t i H B S r e s p o n s e a f t e r t h e s e c o n d a n d t h i r d d o s e of H B V p l a s m a - d e r i v e d v a c c i n e . N U M B E R O F C A S E S % f j A N T I - H B S ( - ) 180 DAYS 210 DAYS

"X

2

= 1 . 1 2 3 8 , 0 . 3 0 > p > 0 . 2 0

F i g . 3 — F r e q u e n c y o f v a c c i n a t e d p e o p l e w i t h g o o d a n t i b o d y r e s p o n s e a f t e r t h e s e c o n d a n d t h i r d d o s e .

rate observed in those studies varied from 74.0

to 100.0%. B e s i d e s , a c o m p a r i s o n between 20

meg by I M route and 2 meg by I D route showed

no significant difference i n the seroconversion

rate

5 H

, though the levels of a n t i - H B s tend to

be lower after reduced doses

2 , 5 1 6

.

I n our material, a low percentage of subjects

(35.0%) accepted to be v a c c i n a t e d a g a i n s t H B V .

T h e m a i n reason for this h i g h refuse was the

unjustifiable fear that plasma-derived v a c c i n e

would be contaminated by h u m a n

immunodefi-ciency v i r u s

6

.

R E D F I E L D et a l

1 4

and M U L L E Y et a l

1 2

em-phazised that vaccine cost remains a major

obs-tacle for the e x p a n s i o n of H B V v a c c i n a t i o n

pro-grams.

T h e low doses schedule used in this study

proved to be effective, a n d , if confirmed in field

s t u d i e s

1 7

, it should be considered in large-scale

programs of i m m u n i z a t i o n a g a i n s t H B V .

R E S U M O

I m u n i z a ç ã o a t i v a contra o v í r u s da H e p a t i t e

B com b a i x a s doses da v a c i n a p l a s m a d e r i v a d a

por v i a i n t r a d é r m i c a .

O e s q u e m a h a b i t u a l m e n t e u t i l i z a d o p a r a

imunização a t i v a contra o vírus d a hepatite B

( V H B ) consiste em 3 doses de 20 m c g por v i a

i n t r a m u s c u l a r (IM) no deltóide. U m dos

proble-m a s quanto à s u a utilização eproble-m l a r g a escala

refe-re-se ao seu custo elevado. P o u c a s publicações

têm se referido a doses menores, de 10 m c g I M

ou 2 m c g i n t r a d é r m i c a ( I D ) . P e s q u i s o u - s e em

300 funcionários d a área d a saúde o a n t i - H B c

total. T o d o s os marcadores foram determinados

pela técnica de E L I S A . E m 43 (14,3%) o m a r c a

-dor foi positivo, correspondendo a 9 (3,0%) com

A g H B s e a 34 (11,3%) com a n t i - H B s . A o s 257

fun-cionários sem a n t i - H B c propôs-se u m esquema

de v a c i n a ç ã o , que foi aceito por 90 (35,0% ). I d a d e

média de 37,4 ± 8,4 anos, limites de 22 - 56 anos

e 68 do sexo feminino. E s q u e m a : 3 doses de 2

meg por v i a I D com intervalos de 1 e 6 meses.

O a n t i - H B s , pesquisado após a 2ª dose mostrou

se positivo em 74 (82,2%) e após a 3ª dose em

80 (88,9%) — diferença não s i g n i f i c a t i v a . C o n t u

do, a quantificação do a n t i - H B s mostrou níveis

10 vezes a c i m a do " c u t - o f f em 29 (32,2%) e em

77 (85,5%r) após a 2ª e 3ª doses, respectivamente

(p < 0,001). Portanto, o esquema proposto

mos-trou-se válido p a r a este tipo de população e,

ape-sar d a freqüência semelhante de sero-conversão

após a 2? e 3? doses, h á necessidade desta ú l t i m a

p a r a aumentar o título de anticorpos.

A C K N O W L E D G M E N T S

We are grateful to Doctors J O S É D I R C E U

P E R E I R A , J O S É F R U T O S D E O L I V E R A , LU¬

C I O O B A , Nurses C A T A R I N A O S A W A and LO¬

R E M A R X for the technical assistance. T h e

revi-sion of the manuscripts was made by Nurse H A N ¬

N E L O R E S P E I E R L and Doctors Z I L D A P A E S

D E B A R R O S M A T O S and W I L S O N M A T T O S

to w h o m we are deeply indebted.

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