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Influence of adjuvant on glycoprotein immunotherapy of recurrent genital herpes
II-30 Herpes s i m p l e x v i r u s t y p e 2 g e n i t a l
infection in male g u i n e a p i g s .
D.I. Bernsteln, D.
Stephanopolous, M.G. Myers. J.N. Gamble Inst. of Med. Res., Cincinnati, Ohio; Children'~ Hospital Res. Fdn., Cincinnati, Ohio, USA. A small animal model of genital herpes simplex virus (HSV) infection Is not available to investigate the pathogenesls in males. Hartley male ~ulnea pigs were Infected with 105-10 6 pfu of HSV-2 MS strain by inoculation onto a small abraded area on the medial thigh. Animals developed vesicular lesions in the genital area Includ~ng penile lesions: the proportion with penile lesions w~s inoculum size dependent, at I0~ pfu 9 of 24 developed penile lesions vs. I! of 12 at I0 p f u . Urethral shedding of HSV during the acute infection also appeared to be dependent upon Inoculum slze (50% vs. 92E). During the acute infection virus was detected in tissue homogenates of the peripheral nerve, lumbosacral dorsal root ganglia (DRG), spinal cord, brain, vas deferens, epididymls, testes, seminal vesicle and prostate. After recovery from the acute infection spontaneous recurrent lesions developed in all 24 animals examined. Animals developed from I-8 recurrences (avg. + S.D. 4.7 + 1.9) which lasted for I-6 days (1.8 + 1.2 days). Intermittent asymptomatlc--urethral ~ h e d d i n g was detected in 4 of 24 an~ma]~ after recovery from the acute disease. Persistent virus was detected hy cocultlvation of DRG, vas deferens, seminal vesicle, epldldymis and testes. Th~s animal model bas much in common with that seen in men and should prove useful for the study of the pathophysioloKy of male genital HSV-2 infections and be useful in the study of antlvlra] a~entq.
II-31 Influenoe of adjuvant on glycoprotein immunotherapy of recurrent genital hazl)ea. L.R. Stanberry, C.J. Harrison, D.I. Bernstein, R.L. Burke and M.G. Myers. Children's Hospital Research Foundation, C i n c i n n a t i , OH, a n d C h i r o n C o r p o r a t i o n , E m e r y v i l l e , CA, U . S . A . The administration of H S V g l y c o p r o t e i n s (gp) to a n i m a l s with established HSV latency augments host immune response and reduces the f r e q u e n c y a n d s e v e r i t y of r e c u r r e n t H S V d i s e a s e (J.I.D. 157:156, 1988). S i m i l a r g p e f f e c t s o n i m m u n e r e s p o n s e and o n t h e d e g r e e of p r o t e c t i o n against primary HSV infection are adjuvant dependent (J.I.D. 155:914, 1 9 8 7 ) . We, t h e r e f o r e u n d e r t o o k a s t u d y t o d e t e r m i n e t h e i m p o r t a n c e of a d j u v a n t s in H S V g l y c o p r o t e l n i m m u n o t h e r a p y of r e c u r r e n t g e n i t a l h e r p e s . A f t e r r e c o v e r y f r o m i n i t i a l g e n i t a l h e r p e s , 69 H a r t l e y g u i n e a p i g s w e r e randomized to receive nothing or a genetically engineered HSV-1 glycoprotein B a n d D (gBgD) m i x t u r e w i t h o r w i t h o u t a d j u v a n t o n d a y 21 and day 42 p o s t HSV inoculation. T h e m e a n ± S.E. days animals e x p e r i e n c e d r e c u r r e n t l e s i o n s (days 22-84) was: C o n t r o l = 1 7 . 8 ± 1 . 7 ; g B g D no a d j u v a n t - 1 7 . 6 ± 1.7; g B g D + A d j u v a n t #1 = 1 1 . 8 ± 1 . 7 ; g B g D + a d j u v a n t #2 = 1 1 . 6 ± 2 . 0 ; g B g D + a d j u v a n t #3 = 1 6 . 5 ± 2 . 3 . These data indicate that effective treatment of established herpesvirus infections with immunogenic viral glycoproteins is a d j u v a n t d e p e n d e n t .
142
infection in male g u i n e a p i g s .
D.I. Bernsteln, D.
Stephanopolous, M.G. Myers. J.N. Gamble Inst. of Med. Res., Cincinnati, Ohio; Children'~ Hospital Res. Fdn., Cincinnati, Ohio, USA. A small animal model of genital herpes simplex virus (HSV) infection Is not available to investigate the pathogenesls in males. Hartley male ~ulnea pigs were Infected with 105-10 6 pfu of HSV-2 MS strain by inoculation onto a small abraded area on the medial thigh. Animals developed vesicular lesions in the genital area Includ~ng penile lesions: the proportion with penile lesions w~s inoculum size dependent, at I0~ pfu 9 of 24 developed penile lesions vs. I! of 12 at I0 p f u . Urethral shedding of HSV during the acute infection also appeared to be dependent upon Inoculum slze (50% vs. 92E). During the acute infection virus was detected in tissue homogenates of the peripheral nerve, lumbosacral dorsal root ganglia (DRG), spinal cord, brain, vas deferens, epididymls, testes, seminal vesicle and prostate. After recovery from the acute infection spontaneous recurrent lesions developed in all 24 animals examined. Animals developed from I-8 recurrences (avg. + S.D. 4.7 + 1.9) which lasted for I-6 days (1.8 + 1.2 days). Intermittent asymptomatlc--urethral ~ h e d d i n g was detected in 4 of 24 an~ma]~ after recovery from the acute disease. Persistent virus was detected hy cocultlvation of DRG, vas deferens, seminal vesicle, epldldymis and testes. Th~s animal model bas much in common with that seen in men and should prove useful for the study of the pathophysioloKy of male genital HSV-2 infections and be useful in the study of antlvlra] a~entq.
II-31 Influenoe of adjuvant on glycoprotein immunotherapy of recurrent genital hazl)ea. L.R. Stanberry, C.J. Harrison, D.I. Bernstein, R.L. Burke and M.G. Myers. Children's Hospital Research Foundation, C i n c i n n a t i , OH, a n d C h i r o n C o r p o r a t i o n , E m e r y v i l l e , CA, U . S . A . The administration of H S V g l y c o p r o t e i n s (gp) to a n i m a l s with established HSV latency augments host immune response and reduces the f r e q u e n c y a n d s e v e r i t y of r e c u r r e n t H S V d i s e a s e (J.I.D. 157:156, 1988). S i m i l a r g p e f f e c t s o n i m m u n e r e s p o n s e and o n t h e d e g r e e of p r o t e c t i o n against primary HSV infection are adjuvant dependent (J.I.D. 155:914, 1 9 8 7 ) . We, t h e r e f o r e u n d e r t o o k a s t u d y t o d e t e r m i n e t h e i m p o r t a n c e of a d j u v a n t s in H S V g l y c o p r o t e l n i m m u n o t h e r a p y of r e c u r r e n t g e n i t a l h e r p e s . A f t e r r e c o v e r y f r o m i n i t i a l g e n i t a l h e r p e s , 69 H a r t l e y g u i n e a p i g s w e r e randomized to receive nothing or a genetically engineered HSV-1 glycoprotein B a n d D (gBgD) m i x t u r e w i t h o r w i t h o u t a d j u v a n t o n d a y 21 and day 42 p o s t HSV inoculation. T h e m e a n ± S.E. days animals e x p e r i e n c e d r e c u r r e n t l e s i o n s (days 22-84) was: C o n t r o l = 1 7 . 8 ± 1 . 7 ; g B g D no a d j u v a n t - 1 7 . 6 ± 1.7; g B g D + A d j u v a n t #1 = 1 1 . 8 ± 1 . 7 ; g B g D + a d j u v a n t #2 = 1 1 . 6 ± 2 . 0 ; g B g D + a d j u v a n t #3 = 1 6 . 5 ± 2 . 3 . These data indicate that effective treatment of established herpesvirus infections with immunogenic viral glycoproteins is a d j u v a n t d e p e n d e n t .
142