Rev. sci. tech. Off. int. Epiz.,
1986, 5 (2), 357-362.
A review of the immune response
to bluetongue virus
M.H. JEGGO*
Summary: This review presents a series of conclusions based on immunologi­
cal studies carried out on bluetongue (BT) infections in mice, sheep and cattle
over the last five years at the Animal Virus Research Institute (A VRI). These
studies highlight the role of both the humoral and cellular components of the
immune response and conclude that current vaccination protocols could be
improved by the use of serial inoculations of monovalent bluetongue virus
(BTV) vaccine preparations.
In identifying areas for further research, this review pinpoints the need to
investigate the possibility of immunotolerance in cattle following a BTV infec­
tion in utero and the importance of this in terms of import/export regulations.
KEYWORDS: Bluetongue virus - Cattle diseases - Cell-mediated immunity Experimental infection - Humoral immunity - Immune tolerance - Mouse Orbivirus - Sheep diseases - Vaccination.
INTRODUCTION
In the past five years, a n u m b e r of studies have been carried out at A V R I on the
immune response t o the inoculation of bluetongue virus (BTV) into mice, sheep and
cattle. In particular, those components of the i m m u n e response involved in reco­
very and protection have been investigated with the aim of improving current con­
trol measures. At all times the BTV strains used to inoculate animals h a d been
plaque purified three times in baby hamster kidney (BHK) cells and thus were rela­
tively avirulent but type-specific. Measurement of the response to virus inoculation
was based on viraemic and pyrexic changes correlated to specific i m m u n e respon­
ses.
Experiments involving the passive transfer of BTV-specific h u m o r a l and cellular
components were carried out to elucidate in more detail those processes involved in
protection and recovery from bluetongue. This review presents the conclusions
from these studies, highlights where they m a y have application in the control of the
disease, and details further research objectives.
SUMMARY OF EXPERIMENTAL RESULTS
AND CONCLUSIONS
1. Studies on the serial inoculation of BTV ( 1 , 2)
Both sheep and cattle were inoculated serially with three different BTV types.
Each virus was inoculated only when n o evidence could be found in the blood of
* Department of Immunology, Animal Virus Research Institute, Pirbright, Surrey GU24 ONF,
United Kingdom.
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the previously inoculated virus. The development of antibodies, not only to the ino­
culated virus but to all other BTV types, was examined and the following conclu­
sions were reached:
(a) The inoculation of one BTV type does not protect an animal from challenge
with other BTV types.
(b) The serial inoculation of two BTV types protects against challenge with a
third BTV type.
(c) The serial inoculation of two BTV types gives rise to a broad heterotypic
antibody response.
2. Studies on the simultaneous inoculation of BTV (3)
The simultaneous inoculation of three BTV types into sheep resulted in the
replication of only two types and a failure in the production of heterotypic antibo­
dies.
3. Studies in mice on the cell-mediated immune response to BTV inoculation
(4, 5, 6)
(a) The inoculation of live BTV into mice gives rise to cytotoxic T lymphocytes
(CTL) whose activity peaks a r o u n d day 7 post-inoculation (pi).
(b) The level of the murine C T L response is dependent on the BTV type and
does not occur when inactivated virus is used.
(c) Anti-BTV murine C T L are capable of varying degrees of cross-reactive lysis
within the BTV g r o u p .
4. Studies on the role of humoral immunity (7)
A series of experiments involving the passive transfer of BTV-specific antibody
in both immune sera and colostrum was carried out to elucidate the role of humoral
immunity in BTV infections. The following conclusions were arrived at:
(a) Immune serum has a role to play in protection from re-infection with BTV.
(b) This protection is type-specific only.
(c) The degree of protection does not correlate with levels of neutralising anti­
body.
5. Studies on the role of cell-mediated responses in protection and recovery from
BTV infections in sheep (8)
These studies involved the identification in sheep of BTV-specific cytotoxic
lymphocytes and their passive transfer in monozygotic animals from an immune to
a non-immune twin.
(a) Sheep produce BTV cytotoxic lymphocytes whose activity peaks around 12
days pi.
(b) These effector cells alone are capable of reducing, to a large extent, the acti­
vity of BTV in s h e e p .
(c) The activity of these cells is short-lived (14 days) but in certain circumstances
they can completely protect sheep from a BTV infection.
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6. Studies involving the inoculation of animals with a second BTV type at various
times following a first BTV inoculation (9).
(a) Animals are protected from challenge with a second BTV type for u p to 14
days after the inoculation of the first virus type.
(b) This occurs through the action of short-lived cross-reactive
lymphocytes and antibody is not involved.
cytotoxic
(c) Other components of the immune system are induced which limit the activity
of these cells to a 10-12 day period post-inoculation (i.e. suppressor cells a n d / o r
anti-CTL idiotype antibody).
(d) A prerequisite to the formation of heterotypic antibody is the inoculation of
two live BTV types administered at least 14 days apart.
7. Studies on BTV intra-uterine infections and the possible development
immuno-tolerance (10, 11, 12)
of
(a) The infection of a foetus early in gestation results in abortion or absorption
of the foetus.
(b) The infection of a foetus in mid or late gestation m a y result in an animal
viraemic at birth, but will result in an animal having BTV-specific antibodies.
(c) The infection of a foetus during the period of gestation when the i m m u n e
system is developing (80 to 120 days in the case of the bovine) may possibly result in
a normal full-term offspring periodically viraemic and incapable of developing
BTV antibodies.
8. Induction of the immune response (13, 14)
(a) Group-specific antibodies are induced
by the outer capsid protein 7.
(b) Type-specific (neutralising) antibodies are induced primarily by outer capsid
protein 2 but also by protein 5.
(c) It is not known what induces cell-mediated i m m u n e responses.
IMPLICATIONS
The conclusions reached in these studies can aid in the control of BTV in two
ways: firstly, through the use of better vaccines and, secondly, t h r o u g h improve­
ment in e x p o r t / i m p o r t control measures.
Considering first vaccine design, it would appear that multivalent preparations
offer no advantage, that neutralising antibody levels are a poor measure of protec­
tion and that repeat inoculation within 14 days is disadvantageous through the
action of cross-reactive C T L . Therefore, it is suggested that a single inoculation of
a live monovalent preparation just prior to the period of virus activity with a
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repeat, one m o n t h later, of a different serotype, will give rise to heterologous
immunity and the desired protection during periods of risk in endemic areas.
However, there are risks associated with live vaccines and this protocol may not
give long-term protection, giving rise to the need to vaccinate annually. There may
also be problems associated with the interfering effect of suppressor cells a n d / o r
anti-idiotype antibody.
In terms of import and export control measures, these studies highlight the need
for further understanding of immuno-tolerance in a BTV infection. The potential
risk from an animal viraemic, but not showing an antibody response, on which current i m p o r t / e x p o r t tests are based, must be evaluated.
AREAS OF FURTHER RESEARCH
These studies have identified areas in which further research into the immune
response to BTV should be conducted. These are:
(a) Further studies on the induction of the ovine cross-reactive cell-mediated
immune response.
(b) Studies on the role of other T-cells (helper and suppressor cells) in modulating the i m m u n e response.
(c) Studies on the potential for immuno-tolerance to develop following intrauterine BTV infection in bovines.
*
* *
REVUE SUR LA RÉPONSE IMMUNITAIRE AU VIRUS DE LA FIÈVRE CATARRHALE OVINE. — M.H. Jeggo.
Résumé : Dans cette revue, l'auteur présente une série de conclusions basées
sur des recherches immunologiques. Celles-ci ont été réalisées sur des infections par le virus de la fièvre catarrhale ovine (BTV = bluetongue virus) chez
la souris, le mouton et le bovin au cours des cinq dernières années à l'Institut
de Recherche sur les virus animaux de Pirbright. Ces études soulignent le rôle
des composantes humorale et cellulaire de la réponse immunitaire et mènent à
la conclusion que les protocoles de vaccination actuels pourraient être améliorés par l'administration d'injections en série de préparations vaccinales à base
de BTV monovalent.
En formulant des thèmes de recherches pour l'avenir, l'auteur estime
nécessaire d'étudier s'il serait possible d'induire une immunotolérance chez les
bovins à la suite d'une infection in utero par le BTV. Il en souligne l'importance du point de vue des réglementations d'importation et d'exportation.
MOTS-CLÉS : Immunité à médiation cellulaire - Immunité humorale - Immunotolérance - Infection expérimentale - Maladies des bovins - Maladies des
ovins - Orbivirus - Souris - Vaccination - Virus de la fièvre catarrhale ovine.
*
**
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REVISIÓN DE LA RESPUESTA INMUNITARIA AL VIRUS DE LA LENGUA AZUL.
— M. H.Jeggo.
Resumen : En esta revisión, presenta el autor una serie de conclusions que se
basan en investigaciones inmunológicas, las cuales fueron realizadas en infecciones por el virus de la lengua azul (BTV = bluetongue virus) en ratones,
ovejas y vacunos en el último lustro en el Instituto de Investigaciones de virus
animales de Pirbright. Los estudios señalan el papel de las componentes
humoral y celular de la respuesta inmunitaria, llevando a concluir que se
podrían mejorar los actuales protocolos de vacunación administrando inyecciones en serie de preparaciones vacunales a base de BTV monovalente.
Al formular temas de investigación para el futuro, estima el autor que hay
que estudiar si se podría inducir una inmunotolerancia en los vacunos después
de una infección in utero por el BTV. Destaca su importancia desde la óptica
de las reglamentaciones de importación y exportación.
PALABRAS CLAVE : Enfermedades de ovinos - Enfermedades de vacunos Infección experimental - Inmunidad de mediación celular - Inmunidad humoral - Inmunotolerancia - Orbivirus - Ratones - Vacunación - Virus de la lengua
azul.
*
* *
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