Differential effects of vaccination against Schistosoma bovis with a recombinant homologous glutathione S-transferase in ruminants

Oral Sessions / Parasitology International 47 (Suppl.) (1998) 133-281

O-0474

DIFFERENTIAL EFFECTS OF VACCINATION AGAINST SCHISTOSOMA BOVIS WITH A RECOMBINANT HOMOLOGOUS GLUTATHIONE S-TRANSFERASE IN RUMINANTS

Schneider D.“. Trottein F.**, Chlppaux J-P.*. Boulannel: y. . Sellin B.*. Capron A.** “Centre de Recherche zur les Mkningites et les Schistosomoses (CERMES/OCCGE/ORSTOM), BP 10887. Niamey, Niger and **Centre d’lmmunologie et de Biologie Parasitaire, Unite Mixte 1NSERM 167~CNRS 624. lnstitut Pasteur, Lille, France. Sc/ti.str?,sso~rto/XII,;.\ i\ the major schistosome species affecting cattle m Africa. Vector control and mass chemotherapy being unrealistic on a large scale. a vaccine strategy has been developed. In this context. the immunogenic and protective capacities of a 28kDa recombinant glutathione S-transferase, cloned from a S. holds adult worm crude extract (rSb28GST). have been evaluated in small ruminants. The immunopenicity of the rSb28GST appeared excellent whatever the ru&nani species (goat, sheep), the -antigenic dosage ( 10 to 200 l.tg Per injection) or the adjuvant (Freund’s Complete Adjuvant. FCA. or Muramyl-Di-Peptide, MDP). 100% of the vaccinated animals developed an antibody response after the boost. In terms of protective effects. the rSb28GST could affect the \chistosome vitality. worm burdens reductions ranging from 39 and 48%. when a single massive infection was applied percutaneously to goats or to sheep. This effect was not found when the cercariae were administered once per OS. Amazingly. a marked anti-schistosome fecundity effect (up 10 60%) - without modification of worm burden - was visualized when goats were orally challenged with fractionnated doses of cercariae. In this latter experiment. the nature of adjuvant (MDPl most likely played a determmant role. Taken as a whole. these data underline the diversity of vaccme effects following different immunization and infection procedures. Together with the resuks obtained in bovines from Sudanese and Zambian research teams. they reinforce the rSb28GST as a valuable tool of preventive control of schistosomosis affecting cattle in Africa.

O-0476

241

sC~ISTOSC+lE KX: ANIXCXN I MX~CED IF?+ y AK0 IL-4 CZNE TRAWKRIFTION IN MURINE SCHISTOSoMIAliIS

Xw

Y,

flu Y,

Tian

Beijing

Tropical

Beijing,

China

The IL-4

Hung

Wdicine

transcripticm

incubated

eqg antigen

Institute

for

IFX-y

were

remved

infectlm

I" the

and

presence

(SEA) or CmA

at 0,3,5,8,10

the spleen

Spleen

cell

IL-4

mRN?m

were

analysed

and

IL-4

mRNAs

were

fclund prcmmently

in 5 and 8 wk infected expression

I" SEA stimulated than

at Swk.

induce and

and

infected

ths regulatim gene

expresslo"

mice

and

ths

the regulation

cells

exists of SEA

including recurred

was observed

at 8wk "or

study

Indicated

IF'N-y

and

in S. ~apon~cum mght

related

the

systemic

mdulatlon

cold in 10 that IL-4

Infected

be immlved

as the Infection

to chronic

lnfezticm SEA

transcription

indeed

regulation

IFN-y

expressed

an appreciable

ConA

Mona

mice.The

formation acute

IL-4

of SEA

resp3"ses from

and mRNA

However,neither

1%~

12wk

mice,

spleen

IFN-y

by RI?-PCX

of IL-4

cells

of schist.osane

and

enhanced

and

in S. -japonicum Infected

Spleens

12 wks after

were

M Research

of mRNps

was investigated

EIALPJcmice. and

X,


in

unmu"e

of granuloma prm

stage.

o-0477

A CRITICAL ROLE OF SKIN DENDRITIC CELLS IN THE INDU0ION OF PROTECI’ION TO SCHISTOSOMA MANSONI INFECTION IN GUINEA-PIGS

o-0475 THE USE OF RECOMBINANT INTERLEUKIN-12 AS AN ADJUVANT FOR THE VACCINATION OF MICE AGAINST EXPERIMENTAL SC.YlSTOSORt4 MANSONI INFECTION BY H&a S. Abdelati, Nashwa I.Ramadan, Maml S. Imail, Sahar S. A.Aziz and Hamed M. Khalil. From the Department of Parasitology, Faculty of Medicine,Ain ShamsUniversity,Cairo, Egypt

Abstract The use of recombinant interleukin 12 (r IL12) as an adjuvant is evaluated for the vaccination of mice against Schistosonta mattsoni experimental infection using homologous crude adult worm antigen. Five groups of mice are used: the first group is given crude adult worm antigen alone, the second given rIL- 12 plus crude worm antigen, the third given rIL-12 only, the fourth is infected without being vaccinated and the fifth group (non vaccinated and non infected) for normal control. The first three groups are challenged by exposure to cercariae after vaccination. Comparison among these groups is done by stool examination for eggs, intestinal perfusion for adult worms and pathological examination for granuloma formation. Further investigation is intended by comparing the level of IFN- gamma in the sera of all five groups.

NH., Sato, H., and Inaba, T. Department of Parasitology, Hirosaki University School of Medicine, Hirosaki, Japan Exposure of guinea-pigs to normal and ultraviolet-attenuated cercariae of Schisrosomu -oni induces different levels of protection to a challenge infection. Using histochemical AT&staining of the epidermal sheet and immunohistochemistry of the skin of guinea-pigs, we have demonstrated more accumulations of ATF%seJMHCclass II-positive cells in the exposure site to attenuated cercariae, when compared with those exposed to normal ones. Using a panel of monoclonal antibodies, we characterized these accumulating cdls to be. closest to Langerhans’ cells, rather than macrophages, and speculated to be blood-home dendritic cells (DC). Temporal changes in the cellular composition of the lymph nodes (SLN) draining the skin sites exposed to normal and attenuated cercariae were compared in guinea-pigs using flowcytometry. Remarkable increases in the proportion of B cells and DC were evident on 2nd day of infection, reached a peak on 4th day. These proportional changes were comparabIe in both animal groups exposed to normal and attenuated cercariae. But, total number of DC in SLN showed diierent kinetics; in animals exposed to normal cercariae, it reached a peak on 2nd day and then gradually reduced, whereas in animals exposed to attenuated ccrcariae, total number of DC reached a higher peak on 4 th day, and then reduced. Suppressed supply of DC by serial 5-bromc-2deoxyuridine treatment every day after infection nduced total number of DC found in SLN on 4th day. It indicates that increased influx of DC from the exposed skin after 2nd day of infection ~cularIy in animals exposed to attenuated cercariae has a n&ion with a newly-formed DC. It is concluded that in addition to antigenic diiemnces between normal and attenuated cerczniae that have been speculated, retention of active schistosomulae in the skin may stimulate accelerated recruitment of newly-formed DC from the bone marrow and these may induce optimal T-responses in SLN. The factor(s) responsible for local recruitment of newly-formed DC is studied focusing on cytokines, e.g., GM-CSF.