Mucosal vaccination against toxoplasmosis

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Mucosal vaccination against toxoplasmosis

D Bout, D Buzoni-Gatel, T Chardès, N Debard, Mn Mevelec

To cite this version:

stratégies.

L’une d’elles consiste à obtenir des

_{protéines purifiées}

_par

_{génie génétique.}

Cette méthode a ainsi été utilisée pour la

production

d’une toxine recombinante

(l’exo-toxine de P

_multocida)

et est

_envisagée

_pour les

_Apx

toxines d’Actinobacillus

pleuro-pneumoniae.

Pour ce

_qui

concerne les

mollicutes,

leur code

_génétique

est

_légèrement

différent du code universel

_(le

codon UGA _{n’est pas} un

codon de terminaison mais code pour le

tryptophane).

De ce

fait,

les

_produits

de tra-duction des

_gènes

des mollicutes sont

tron-qués lorsque

leur

expression

est réalisée dans un

_système

bactérien

_classique

tel

qu’E coli.

Néanmoins,

de nouvelles

_approches

ont été récemment décrites et concernent l’uti-lisation de vecteurs de

_gènes

_spécifiques

des mollicutes ou _{celle de souches}

sup-pressives d’E coli capables

de lire le codon

UGA comme codon

_tryptophane

(Renau-din

et al, 1994 ;

Minion

et al,

1994).

Les pro-téines recombinantes obtenues devraient

permettre

d’élaborer des vaccins de

nou-velle

_{génération.}

Références

Dayalu KI, Ross RF (1990) Evaluation of experimental

vaccines for control of porcine pneumonia induced by Mycoplasma hyopneumoniae. 11 thInternational Pig Veterinary Society Congress 1-5 juillet, Lausanne, Suisse, 83 p

Kobish M, Quillien L, Tillon JP, Wroblewski H ₍₁₉₈₇₎

The Mycoplasma hyopneumoniae plasma

mem-brane as a vaccine against porcine enzootic pneu-monia. Ann lnst Pasteurllmmunol 138, 693-705

Kobish M, Labbé A, Morvan P, Cariolet R ₍₁₉₉₄₎ Eval-uation of a _Mycoplasma hyopneumoniae vaccine in

pigs experimentally infected with Mycoplasma

hyop-neumoniae and Pasteurella multocida. l0th Inter-national _Organisation of _{Mycoplasmology.} 19-26

juillet. Bordeaux, France, 244-245

Minion C, Artiushin S, Van Dyk C, Smiley BK (1994)

Use of a novel opal suppressor strain of Escherichia coli to screen _Mycoplasma hyopneumoniae gene libraries. l0th International Organisation of Mycoplas-mology, 630-631

Mori Y, Hamaoka T, Sato S, Takeuchi S (1988) lmmunoblotting analysis of _antibody response in

swine experimentally inoculted with Mycoplasma hyopneumoniae. Vet Immunot /mmunopaf!o/19, 239-250

Peterson G, Weiss D _{(1990) Response} to _Mycoplasma

hyopneumoniae vaccination in _{nursing piglets.} 11th

International Pig Veterinary Society Congress, 1-5

juillet, Lausanne, Suisse, 84 p

Renaudin J, Marais A, Verdin E, Duret S, Laigret F,

Bové JM (1994) Spiroplasma citri-OricC plasmids: expression of the Spiroplasma phoeniceum spiralin

in S citri. IOM Congr, Bordeaux, France, 583-584 Ross RF, Zimmermann-Erickson B, Young T ₍₁₉₈₄₎

Char-acteristics of _{protective activity} of _Mycoplasma

hyo-pneumoniae vaccine. Am J Vet Res 45, 1899-1905 Young TF, Ross RF (1987) Assessment of antibody

response of swine infected with Mycop/asma hyo-pneumoniae by immunoblotting. Am J Vet Res 48,

651-656

Mucosal vaccination

_against

toxoplas-mosis. D

D Bout,

_Bout,

D D

Buzoni-Gatel,

Buzoni-Gatel,

T T

Chardès,

Chardès,

N Debard MN

_{Mevelec Equipe}

associée INRA

_{d’immunologie}

_parasitaire,

UFR des sciences

_{pharmaceutiques,}

31,

avenue

Monge,

37200

Tours,

France)

Toxoplasmosis

affects over 50% of

sheep,

goat

and

_{pig populations.}

The abortions that it causes

_represent

a

_major

economic

problem

for

_sheep

farmers. It is

_responsible

for over 50% of the abortions of infectious

origin

in

sheep.

Animal

toxoplasmosis

is also a

_public

health risk since the

_majority

of cases of human

toxoplasmosis

results from the

_consumption

of contaminated

sheep

or

_pig

meat.

_Congenital

toxoplas-mosis and

_{immunodeficiency}

neurotoxo-plasmosis

are the severe forms of human infection. There is a clear need for a

vet-erinary

vaccine to

_prevent

animal

toxo-plasmosis

and as a result human

toxo-plasmosis.

The causal

_agent

of

toxoplasmosis, Toxoplasma gondii,

is a

coccidium. The site of

_penetration

into the animal

body

is the intestinal mucosa. This

approach

to vaccination

_by

the mucosal route. In the first

_phase

of our

work,

we

showed that the animals

_developed

humoral and cellular

_immunity

in the intestinal

mucosa. After oral

infection,

IgA

antibodies,

principally

directed

_against

3

_antigens

(SAG1,

GRA4 and

_ROP2)

were

synthe-sized.

_{Intraepithelial}

_CD8ap

₊

_Thy-1

₊

lym-phocytes, cytotoxic

for

enterocytes

infected with

_{T gondii and}

_{producing IFN-y,}

also

appeared

(Chardes

et al,

1994).

In

addi-tion,

we showed that the

_IFN-y

activated the

_enterocyte

and thus inhibited the

multi-plication

of the

_toxoplasm

_{which had} pen-etrated it

_(Dimier

and

Bout,

1993).

This

rational,

_{physiopathological}

and

immuno-logical approach

then led us to

_attempt

vac-cination

_by

the mucosal route

_(Bourguin

et

al, 1993).

Recent work has shown that cholera toxin is a

_{powerful adjuvant}

for the mucosal immune _response

_against

well-defined

_antigens

such as ovalbumin. We have shown that its use _{opens the way} to efficient vaccination

_by

the mucosal route. A total

_antigen

of

_{T gondii}

combined with cholera toxin and administrated

_orally

to the mouse induced 50%

_{protection against}

the 76K strain as assessed on a cumula-tive

_lethality

basis. A substantial reduction in the number of cerebral

cysts

was also observed.

_Experiments

on immunization

_by

the nasal route were then carried out

_using

well-defined

_{antigens (SAG1, GRA4)}

com-bined with cholera toxin.

_Eighty

_percent

pro-tection,

assessed

_by

the number of

cere-bral

cysts,

was, for

example,

obtained with

antigen

SAG1. Excellent correlation was

observed between the

_protection

and the immune response in the intestinal mucosa.

Preliminary protection

results have been observed for another

coccidiosis,

cryp-tosporidiosis.

This

_present

work with

toxo-plasm

is an excellent

_study

model and makes it reasonable to _{suppose that it could} be used as a basis for

_obtaining

similar results

_against

_{many other infectious}

agents.

References

Chardbs T, Buzoni-Gatel D, Lepage A, Bernard F, Bout D _{(1994) Toxoplasma gondii oral} infection induced specific cytotoxic CD8aØ+ Thy-1 gut intraepithelial lymphocytes, lytic for _{parasite-infected} enterocytes.

J Immunol 153, 4596-4603

Dimier I, Bout D (1993) Rat intestinal epithelial cell line IEC-6 is activated _{by rIFN-yto} inhibit replication of the coccidian _{Toxoplasma gondii.} Eur J Immunol 23,

981-983

Bourguin I, Chard6s T, Bout D (1993) Oral immunization

with Toxoplasma gondii antigens in association with cholera toxin induces enhanced protective and cell-mediated immunity in C57BU6 mice. Infect Immun

61,2082-2088

Vaccination contre les coccidioses aviaires. P

_{P Péry}

_{Péry 1}

_,

P Yvore P Yvore 2

₂

_,

F F Laurent

2

Laurent

_,

₂

MM

Bessay

(!

INRA,

virologie

et

_immunologie

moléculaires,

78350

_{Jouy-en-Josas;}

2

INRA,

pathologie

aviaire et

_{parasitologie,}

37380

Nouzilly, France)

En matière de coccidiose

aviaire,

et

_jusqu’à

ces dernières

années,

il

_n’y

_{avait pas} d’al-ternative à la

_{chimiothérapie}

pour la

protec-tion des oiseaux. Actuellement une vaccina-tion à l’aide d’un vaccin vivant est mise en

place

dans toute

_l’Europe

à l’exclusion de la France. Le vaccin est constitué de souches dont la

_{période prépatente}

est

_plus

courte que la normale

(souches

dites

_précoces)

et

qui

ont conservé

_après

sélection un _bon

pou-voir

_immunogène,

mais ont un

_pouvoir

patho-gène

atténué. Il contient un

_mélange

des 7

espèces

de coccidies les

_{plus répandues,}

une deuxième souche d’Eimeria maxima

ayant

été

_rajoutée

pour tenir

compte

de la variabilité de cette

_espèce.

Ce vaccin est effi- i-cace, mais des

_problèmes

subsistent

_(coût

et difficulté de

_production,

absence de

mar-queurs).

Ce succès n’a pas

empêché

les recherches vers un vaccin moléculaire et,