Vaccin recombinant contre le calicivirus de la septicémie hémorragique du lapin (RHDV)

HAL Id: hal-02712273

https://hal.inrae.fr/hal-02712273

Submitted on 1 Jun 2020

HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci- entific research documents, whether they are pub- lished or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Vaccin recombinant contre le calicivirus de la septicémie hémorragique du lapin (RHDV)

Jean-François Vautherot, S. Laurent, G. Le Gall, J.P. Morisse, Denis Rasschaert

To cite this version:

Jean-François Vautherot, S. Laurent, G. Le Gall, J.P. Morisse, Denis Rasschaert. Vaccin recombinant

contre le calicivirus de la septicémie hémorragique du lapin (RHDV). Veterinary Research, BioMed

Central, 1995, 26 (3), pp.206-207. �hal-02712273�

Internationally, fish vaccination was

launched in the US between 1975 and 1978

by ^{the use of 2} antibacterial vaccines inten- ded for protection against vibriosis and yer- siniosis, ² diseases that did not exist in France at these times. Our laboratory ^was mainly ^{involved in} investigations ^{on antiviral}

vaccines for salmonid fish. The aim was to

provide ^an alternative prevention strategy

to the control policy ^{measures that have}

been refused so far by fish farmers. The work encompassed infectious pancreatic

necrosis and more specifically viral hae-

morrhagic septicaemia (VHS). For this latter

infection, ^{the work} began ^{with an} injectable

inactivated vaccine and later, somewhat

belatedly, with different attenuated ’living’

vaccines whose effectiveness even through-

out field trials, could not overcome limiting

concerns about their potential ^risks (de ^Kin- kelin, 1988).

It was at this time that a third virosis, infectious haematopoietic ^necrosis (IHN), emerged in France (1987-1988). IHN is cli-

nically ^{similar to} VHS but shares no cross-

immunity with it. The molecular biology ^era

was reached when joint investigations ^with Eurogentec, ^a genetic engineering ^com- pany, started. Protection of trout against VHS, using ^a recombinant subunit vaccine

resulting ^{from the} expression ^of gene ^from the viral glycoprotein in Escherichia coli or

Saccharomyces cerevisiae, ^{failed. Later} on, a recombinant baculovirus vaccine ex-

pressed in insect cells was found to be

immunogenic ^and protective against ^VHS

but only when delivered by injection (Lecocq-Xhonneux ^{et al,} 1994). ^{This com-} plicated ^and expensive process ^sums up what we knew in 1977.

In conclusion, i) inactivated viruses are

protective when delivered by injection ^but

their cost of production ^and delivery ^makes

them economically unacceptable. ii) ^Recom-

binant subunit vaccines were expected ^to

be cheap and easy ^to produce but it is not

exactly ^{the case and} they ^{failed to} be pro-

tective, ie the vaccine to VHS was not effec- tive and vaccine to IHN (Leong ^and Fryer, 1993) ^was questionable. iii) ^The only ^effec-

tive vaccine to VHS suitable for water- borne

delivery ^{was made with a} live attenuated virus variant but it encountered strong ^hin-

drances from regulations and its field use was doomed to failure by ^{the recent occur-}

rence of IHN that killed VHS-protected ^fish.

iv) ^An anti-virus vaccine for fish should be an

autoreplicative ^vaccine (deleted ^{virus or}

gene recombined virus). v) ^The develop-

ment of an ideal vaccine takes time during

which specific ^viroses spread ^{and/or new}

viroses appear resulting in double or triple

virus contamination of farmed fish popula-

tions. This makes the concept ^{of control} policy of viroses more acceptable ^{to fish far-}

mers in the near future. Thus, in the pre-

sence of a fish viral disease, effective

immunoprophylactic ^{control must be set} up

quickly after the condition is reported. ^{It must}

also be relatively inexpensive, otherwise it will be unprofitable. In view of all these

constraints, ^{there are} only very slight

chances of being ^{able to} develop ^success-

ful fish vaccines that combat against ^viral

infections.

References

de Kinkelin P (1988) Vaccination against viral haemor- rhagic septicaemia. ^In: Fish Vaccination. (AE Ellis, ed) ^Academic Press, London, UK, 172-192

Lecocq-Xhonneux F, Thiry M, Deur I et al (1994) ^A

recombinant viral haemorrhagic septicaemia ^virus glycoprotein expressed ⁱⁿ insect cells induces pro- tective immunity in rainbow trout. J Gen Viral 75, 1579-1587

Leong JA, Fryer JL (1993) Viral vaccine for aquaculture.

Annu Rev Fish Dis 3, 225-240

Vaccin recombinant contre le calicivirus

de la septicémie hémorragique ^du lapin

(RHDV). JF Vautherot JF Vautherot 1 , ^{S Laurent} S Laurent 1 1 , ^{G Le} G Le

Gall JP Morisse D Rasschaert

(

1 ^{INRA, unité de} virologie ^et d’immunologie moléculaires, domaine de Vilvert, ⁷⁸³⁵²

Jouy-en-Josas; ^{2 CNEVA, unité de} patho- logie cunicole, ²²⁴⁴⁰ Ploufragan, France)

Le syndrome hémorragique ^{viral du} lapin (RHDV) ^a pour agent ^{causal un} calicivirus, virus dont la capside résulte de la multimé- risation d’une seule protéine, Vp60. ^{En rai-}

son de l’absence de système de culture du virus, les vaccins inactivés ont été jusqu’à présent préparés ^à partir de foies d’animaux infectés.

Le choix d’une stratégie vaccinale repo- sant sur l’utilisation de Vp60 recombinante

permettait de résoudre plusieurs problèmes :

-

obtention de préparations antigéniques

en quantité importante, homogènes ^{et aisé-}

ment purifiables ;

-

absence de pathogénicité résiduelle ;

-

démonstration du rôle de la Vp60 ^dans

l’induction d’une protection.

Le système Baculovirus/Sfg ^s’est imposé

par ^sa simplicité ^{et ses} qualités ^comme pre- mier système d’expression pour la Vp60 ^du

virus RHVD. La Vp60 produite ^en grande quantité par les baculovirus recombinants

se multimérise pour former des pseudo-par-

ticules (VLP) morphologiquement identiques

aux virions (Laurent ^{et al,} 1994).

L’utilisation de ces VLP dans un essai de vaccination par voie parentérale ^{a mon-}

tré une efficacité égale à celle des prépa-

rations commerciales. Ayant validé l’utilisa- tion de la Vp60 recombinante pour la vaccination des animaux contre la RHVD,

nous collaborons avec l’équipe ^{d’A Milon} (ENV Toulouse) pour l’obtention d’un ^vaccin recombinant Myxomatose/RHVD.

Référence

Laurent S, Vautherot JF, Madelaine MF, Le Gall G, Rasschaert D (1994) Recombinant rabbit hemor-

rhagic disease ^virus capsid protein expressed ⁱⁿ baculovirus self-assembles into viruslike particles and induces protection. J Virol68, ^6794-6798

Defective adenoviruses as virus vectors for veterinary vaccines. M M Éloit (INRA, Éloit (INRA, École nationale vétérinaire dalfort, ^{unité de} génétique moléculaire-génétique ^virale,

94701 Maisons-Alfort, France)

We are studying ^the potency ^{and the} safety

of replication defective Ad5-based vectors

(E1A defective) for the vaccination of ani- mals. Use of replication defective aden- oviruses can be compared ^to genetic ^immu-

nisation. In both _cases, the foreign gene ^is persistent ^{for a} long ^time, during ^{which its} product ^is correctly presented ^{to the immune} system ⁱⁿ association with the CMH. This

approach ^{leads to some} advantages (biosafety, adequate processing of the anti- gen, long-lasting immune response ^and induction of a mucosal immunity). ^{Ad5 wild-} type ^{is able to} replicate ^at high titre in human cells and at medium titres in Vero (monkey),

GBK22 (bovine) ^{and PK15} (pig) cell lines. It does not replicate ^{in MDCK3} (canine),

G355-5 (feline) ^{and 3T3} (murine) cell lines.

Nevertheless, Ad5 vectors can introduce

foreign genes in vitro into all these cell lines, and even into avian and fish cells, showing

that the virus cycle is abortive at a step ^fol- lowing ^the penetration of the virion and the

decapsidation of the DNA. A number of mammalian species (eg, ^{mouse, rat, cattle,} pig, dog ^and cat) ^{and even chickens can}

mount an immune response against ^{a for-} eign protein inserted in Ad5 vectors. Nasal, muscular and subcutaneous routes are effi- cient methods of administration in mice, while the oral route proved ^to be inefficient in this species. Intraduodenal administra- tion in pigs (a ^first step of evaluation of

gastroprotected preparations) ^{led to the}

development ^{of a low} antibody response,