WORLD H E A L T H ORGANIZATION ORGANISATION M O N D I A L E D E L A SANTÉ
V[R/RC/74.24 ENGLISH ONLY
(Arbo)
MEETING OF DIRECTORS OF WHO REFERENCE CENTRES FOR ARBOVIRUSES; 1-5 A p r i l CHLAMYDIAE AND R I C K E T T S I A E 1974
INDEXED
Geneva,
YELLOW F E V E R V A C C I N E by Dr WHO Regional Institut Y. Robin, Pasteur,
THERMOSTABILITY
- 1î
WA»-^
Director for Arboviruses Dakar, Senegal
Reference Centre
1.
Previous The heat
studies stability since of dried the of al. yellow (1929) fever vaccine preparations to be u s e d w h e r e v e r the with first a to yellow of were i.e. dried at associate has the the been a source i.e. of of in infectiLater was out They its titre an
constant tropical vity Fox with
anxiety, areas. the (1970)
vaccine is
fever exists,
Sawyer et confirmed i n the on the
maintenance presence (1947) lost
standard factor
dessication, these storage of
low l e v e l
residual humidity.
St G a r d
studies time at
and showed m o r e o v e r t h a t vaccines. d i f f e r e n t temperatures temperatures above -5°C of it
of a i r carried
unfavourable detailed after showed t h a t
B u r u s s 8c H a r g e t t dried had
studies i f
survival
17D v a c c i n e . much o f
the
v a c c i n e was s t o r e d storage. (1953) showed t h a t
two y e a r s '
Hahn ScDugher lost much 1.5 less All transport below the 2. 2.1 fever to 2.0
at
temperatures d u r i n g the
of -4°C first
the year.
vaccine preparations Subsequent losses
studied were
decimal
logarithms of
titre
appreciable. these of studies If l e d to the publication of recommendations be k e p t at a temperature concerning the a below - 2 5 ° C . ice. storage I n most and cases
the
17D v a c c i n e : p o s s i b l e they transported
a l l the
v a c c i n e s must
permanently at carbon dioxide
temperature
-5^0.
s h o u l d be s t o r e d
vaccines are Present A first
in containers
refrigerated with
studies study (Robin et the al., 1971) compared the The p u r p o s e sufficiently heat of stability of eight batches of the to yellow
vaccine from d i f f e r e n t c o u n t r i e s . under find which to a preparation that was
this to
s t u d y was t o be used as an
determine
conditions attempt standard, The (16.596 the of it for The Total the sixth loss
v a c c i n e s h o u l d be
transported
i n p a r t i c u l a r l y hot
c l i m a t e s and international
stable
mean t i t r e LD50 of per week,
of
the which above
vaccine preparations at a plateau from 0.5 that the to
was m a i n t a i n e d a t Titre +5°C.
3 log LDJQ/O.OS continued to least A t 22°C not have be six
ml lost until level but an months.
dose) after
f o r s i x months
- 2 0 ° C and +5^C, l o g at dose loss -20''C and at
b e g a n w h i c h was m a i n t a i n e d f o r a t 0.6 f o r three months. 22°C l o g as does being 0.58
titre
ranged be s a i d
the too
average great
titres on the
remains
1000 L D 5 0 p e r average
Variations compared w i t h
occurred, the
can n e v e r t h e l e s s two w e e k s a t
a period of
two weeks
effect
vaccine t i t r e , -20°C.
vaccine kept
issue of this document does not constitute It should not be reviewed, Authors alone in signed
C e document ne constitue pas une publication, II ne doit faire l'objet d'aucun compte rendu ou r é s u m é ni d'aucune citation sans l'autorisation de l'Organisation Mondiale de la S a n t é . Les opinions exprimées dans les articles s i g n é s n'engagent que leurs auteurs.
formal publication.
abstracted or quoted without the agreement of the World Health Organization. are articles. responsible for views expressed
VIR/RC/74.24
(Arbo)
page 2 I t was not p o s s i b l e i n t h i s s t u d y to d e t e r m i n e the c o n n e x i o n between s t a b i l i t y and r e s i d u a l h u m i d i t y l e v e l , s i n c e we d i d not know t h a t l e v e l f o r most of the v a c c i n e s . tho
R e c e n t l y R o b i n s o n ( l t ) 7 2 ) , u s i n g a gas chromatograpliy metliod to measure r e s i d u a l w a t e r I n s m a l l p o x v a c c i n e , showed t h a t t h e r e was no d i r e c t c o r r e l a t i o n between r e s i d u a l water and thermostability. The p r e l i m i n a r y r e s u l t s o b t a i n e d seem to suggest t l i a t a v a c c i n e poor i n p r o t e i n n i t r o g e n may be r e l a t i v e l y u n s t a b l e i f the r e s i d u a l water l e v e l i s v e r y low. The a d d i t i o n of ^"^0 sodium g l u t a m a t e d u r i n g f r o e z e - d r y i n g does not seem to improve the s t o r a g e p r o p e r t i e s of the v a c c i n e ( p e r s o n a l e x p e r i m e n t s ) , 2,2 In a second s t u d y we attempted t o d e t e r m i n e the r a t e of d e g r a d a t i o n of the 170 v a c c i n e p r e p a r a t i o n a t t h r e e temperatui'es: 28°C, 36,2°C, and 45^C, b a s i n g our work on t h a t of G r e i f f h. R i g h t s e l ( 1 9 6 6 ) , The ampoules o f d r i e d v a c c i n e were removed a f t e r 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 15 and 20 days a t +28"C, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 15 days a t 36.2''C and
12, 0,5, 1,
2, 3, 4, 5, 6, 7 and 8 days at 15'C. The f o l l o w i n g r e s u l t s were o b t a i n e d : i f a l o s s i n t i t r e of one d e c i m a l l o g a r i t l i m compared w i t h t h e i n i t i a l t i t r e i s t a k e n as the c r i t e r i o n i t took: ( 10 days a t 28°C to r e a c h t h a t p o i n t > 6 days at 3 6 . 2 ° C ( 3 days a t 45''C I f the t h e r m o s t a b i l i t y of t h i s v a c c i n e p r e p a r a t i o n i s compared w i t h the s t a b i l i t y of measles v a c c i n e under the same t e m p e r a t u r e c o n d i t i o n s ( G r e i f f & R i g h t s e l , 1966), i t i s found t h a t t h e 17D v a c c i n e i s more heat s t a b l e than the measles v a c c i n e w h i c h shows a l o s s of one decimal logarithm i n t i t r e a f t e r : ( 5 days a t 23°C 36.2''C
\ 2 days at
( 0.3 3. C o n c l u s i o n s and recommendations
days a t 45"C
These as y e t from f r a g m e n t a r y s t u d i e s have made i t p o s s i b l e to a s s e s s the c o u r s e of breakdown of f r e e z e - d r i e d y e l l o w f e v e r v a c c i n e s s u b j e c t e d t o h i g h t e m p e r a t u r e s . This breakdown i s q u i t e r a p i d s i n c e a t 28 "C t h e r e i s a l o s s of one d e c i m a l l o g a r i t h m i n 10 d a y s . The e f f e c t o f h e a t on the v i r u s p a r t i c l e d i f f e r s a c c o r d i n g t o whether the p a r t i c l e suspended i n a l i q u i d medium o r i s p a r t of a f r e e z e - d r i e d p r e p a r a t i o n . is
The s t u d i e s by G r e i f f & R i g h t s e l (1966) on the measles v i r u s , which has s i m i l a r p h y s i c o c h e m i c a l c h a r a c t e r i s t i c s to t h o s e of the y e l l o w f e v e r v i r u s (RNA, e n v e l o p e , s e n s i t i v i t y t o l i p i d s o l v e n t s , a c i d pH and t e m p e r a t u r e ) showed t h a t w h i l e i n a c t i v a t i o n o f the v i r u s i n s u s p e n s i o n i s due m a i n l y to a d e n a t u r a t i o n of the p r o t e i n s , i n the case of f r e e z e - d r i e d p r e p a r a t i o n s heat e x e r c i s e s i t s e f f e c t on the r i b o n u c l e i c a c i d . S t u d i e s s h o u l d t h e r e f o r e be d i r e c t e d towards a s e a r c h f o r r i b o n u c l e i c a c i d p r o t e c t o r s .
VIR/RC/74.24 page 3
(Arbo)
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