Vaccin recombinant contre le calicivirus de la septicémie

Internationally, fish vaccination was
launched in the US between 1975 and 1978
by the use of 2 antibacterial vaccines intended for protection against vibriosis and yersiniosis, 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 haemorrhagic 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 throughout field trials, could not overcome limiting
concerns about their potential risks (de Kinkelin, 1988).
It was at this time that a third virosis,
infectious haematopoietic necrosis (IHN),
emerged in France (1987-1988). IHN is clinically similar to VHS but shares no crossimmunity 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,
recombinant baculovirus vaccine expressed in insect cells was found to be
immunogenic and protective against VHS
but only when delivered by injection
(Lecocq-Xhonneux et al, 1994). This complicated and expensive process sums up
what we knew in 1977.
a
In conclusion, i) inactivated viruses are
protective when delivered by injection but
their cost of production and delivery makes
them economically unacceptable. ii) Recombinant 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
tive and vaccine to IHN
not effec-
and
(Leong
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 hindrances from regulations and its field use
was doomed to failure by the recent occurrence 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 development 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 populations. This makes the concept of control
policy of viroses more acceptable to fish farmers in the near future. Thus, in the presence 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 successful fish vaccines that combat against viral
infections.
References
de Kinkelin P
(1988) Vaccination against viral haemorrhagic septicaemia. In: Fish Vaccination. (AE Ellis,
ed) Academic Press, London, UK, 172-192
Lecocq-Xhonneux F, Thiry M, DeurI et al (1994) A
recombinant viral haemorrhagic septicaemia virus
glycoprotein expressed in insect cells induces protective 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
Laurent 1
1
, G Le
(RHDV). JF Vautherot 1, S Laurent
D Rasschaert
Gall
JP Morisse
(1 INRA, unité de virologie et d’immunologie
moléculaires, domaine de Vilvert, 78352
CNEVA,
Jouy-en-Josas;2
logie cunicole,
22440
unité de pathoPloufragan, France)
Le
syndrome hémorragique viral du lapin
(RHDV) a pour agent causal un calicivirus,
virus dont la capside résulte de la multimérisation d’une seule protéine, Vp60. En raison 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 reposur l’utilisation de Vp60 recombinante
permettait de résoudre plusieurs problèmes :
sant
obtention de
préparations antigéniques
quantité importante, homogènes et aisément 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 premier 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-particules (VLP) morphologiquement identiques
aux virions (Laurent et al, 1994).
-
en
-
-
L’utilisation de ces VLP dans un essai
de vaccination par voie parentérale a montré une efficacité égale à celle des préparations commerciales. Ayant validé l’utilisation 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-
virus capsid protein expressed in
baculovirus self-assembles into viruslike particles
and induces protection. J Virol68, 6794-6798
rhagic disease
Defective adenoviruses as virus vectors
for veterinary vaccines.M MÉloit
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 animals. Use of replication defective adenoviruses can be compared to genetic immunisation. 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 antigen, long-lasting immune response and
induction of a mucosal immunity). Ad5 wildtype 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 following 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 foreign protein inserted in Ad5 vectors. Nasal,
muscular and subcutaneous routes are efficient methods of administration in mice,
while the oral route proved to be inefficient
in this species. Intraduodenal administration in pigs (a first step of evaluation of
gastroprotected preparations) led to the
development of a low antibody response,