Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 104(2): 246-251, March 2009
online | memorias.ioc.fiocruz.br
Veterinary vaccines against Toxoplasma gondii
Elisabeth A Innes/+, Paul M Bartley, Stephen Maley, Frank Katzer, David Buxton
Moredun Research Institute, Pentlands Science Park, EH26 OPZ Bush Loan, Edinburgh
Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded
animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts
and following infection most animals develop adaptive humoral and cell-mediated immune responses. The develop-
ment of protective immunity to T. gondii following natural infection in many host species has led researchers to look
at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range
of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent
congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding
in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary
vaccines against T. gondii.
Key words: Toxoplasma gondii - veterinary - vaccine
Toxoplasma gondii has a very wide host range and
is thought to be able to infect all warm blooded animals
making it a highly successful parasitic organism. There
is also a wide spectrum of disease manifesting within the
various host species and different components contribute
to the severity of the disease including host species, im-
mune status of host and biological and genetic variation
within the parasite (Innes 1997). T.gondii can cause acute
fatal infection in some host species such as marsupials and
new world monkeys that have evolved largely away from
the cat (the definitive host of T. gondii) and have therefore
not developed resistance to the parasite (Dubey & Beattie
1988). In farm livestock species such as sheep and goats,
congenital infection is common which may result in abor-
tion and neonatal mortality (Buxton 1998). Animals bred
to produce meat for human consumption may be persis-
tently infected with T. gondii, contained within tissue
cysts in the muscles and viscera and can act as important
sources of infection for people. A very important animal
in the life cycle of T. gondii and the epidemiology of the
disease is the cat. Following a primary infection, cats will
shed millions of oocysts in their faeces that can survive
for 12-18 months in the environment, depending on cli-
mactic conditions, and are an important source of infec-
tion for grazing animals (Tenter et al. 2000). Therefore a
range of different veterinary vaccines are required to help
control T. gondii infection which include vaccines to pre-
vent congenital toxoplasmosis, reduce or eliminate tissue
cysts and to prevent oocyst shedding (Innes & Vermeulen
2006). In this paper we will discuss some of the history,
challenges and progress in the development of veterinary
vaccines against T. gondii.
Financial support: Rural and Environment Research, Analysis Direc-
torate, Scottish Government
+ Corresponding author: email@example.com
Received 10 October 2008
Accepted 3 December 2008
Vaccines to prevent congenital toxoplasmosis
Toxoplasma was first recognised to be an important
pathogen in livestock species following reports from
New Zealand describing T. gondii organisms in placen-
tal tissue from aborting sheep and within an aborted
ovine foetus (Hartley et al. 1954, Hartley & Marshall,
1957). The authors initially described this as New Zea-
land type II abortion and subsequently there were other
reports of a similar disease in sheep occurring in oth-
er countries worldwide including Australia, UK and
Europe. At the time ovine toxoplasmosis was first de-
scribed in New Zealand, the route of transmission was
still unclear. As sheep are herbivores it suggested that
there may be another as yet undiscovered route of trans-
mission that did not involve congenital transmission or
the consumption of T. gondii tissue cysts within infected
meat. The discovery in the late 1960’s that cats could
shed a new form of the parasite in their faeces that was
very stable in the environment (Hutchison 1965) led to
the recognition of the cat as the definitive host of the
parasite (Frenkel et al. 1970, Hutchison et al. 1970, Fer-
guson et al. 1974) and the oocyst as a major source of in-
fection for both animals and people, as well as being an
important source of environmental contamination. The
discovery of T. gondii occysts helped to explain trans-
mission of infection to herbivores and therefore how the
disease was spread within and between flocks of grazing
animals. Ovine toxoplasmosis occurs in temperate sheep
rearing countries worldwide where the climatic condi-
tions favour oocyst survival (Buxton & Rodger 2008).
In 2007, the population of sheep and goats in the EU
reached 108,9 million (http://epp.eurostat.ec.europa.eu)
and while the incidence of toxoplasmosis is difficult to
define with accuracy, a study in UK suggested that the
disease was responsible for 1-2% of neonatal losses per
annum (Blewett & Trees 1987). If this incidence was ex-
trapolated throughout Europe, this would mean a loss of
around 1,5-2 million animals.
Young cats tend to become infected with T. gondii
when they go hunting for the first time and eat wild ro-
Veterinary vaccines against T. gondii • Elisabeth A Innes et al.
dents and birds. Around three-10 days after infection,
cats start to shed oocysts for two-three weeks (Dubey
& Beattie 1988). Each infected cat may shed 100 mil-
lion oocysts into the environment and as few as 200
sporulated oocysts can cause congenital disease in na-
ïve sheep (McColgan et al. 1988). Infection in sheep is
associated with contamination of feed or grazing land
with sporulated oocysts (Plant et al. 1974, Faull et al.
1986). There is also an increasing likelihood of sero-
prevalence related to age of the animal indicating that
there is extensive environmental contamination with oo-
cysts and that most infections in sheep occur following
birth (Waldeland 1977, Lunden et al. 1994). Some recent
data suggests that in some circumstances persistently in-
fected sheep may transmit the parasite to the foetus in
subsequent pregnancies (Duncanson et al. 2001, Morley
et al. 2005). These observations are interesting, although
do appear to be uncommon. A further more complete
study provided confirmatory evidence that there does
not appear to be significant congenital transmission of
T. gondii from persistently infected sheep to their off-
spring (Rodger et al. 2006). Clinical symptoms in sheep
include foetal death, production of a mummified foetus,
still born lamb or birth of a live but weak lamb (Buxton
& Rodger 2008). A significant factor in determining se-
verity of disease is the stage of gestation when infection
occurs, the earlier in gestation the more severe the con-
sequences for the developing foetus (Watson & Beverley
1971, Hartley & Moyle 1974, Blewett et al. 1982).
In a naïve sheep, following ingestion of oocysts, the
parasites excyst in the gut releasing sporozoites which
are able to actively invade and multiply within the gut
cells. The tachyzoite stage of the parasite multiplies
asexually by a process of endodyogeny within a para-
sitophorous vacuole and then the parasites eventually
rupture from the cell and go on and invade further cells
(Lingelbach & Joiner 1998). By day four following infec-
tion, tachyzoites may be found in the mesenteric lymph
node (Dubey 1984) and the parasites are also found in
the circulation where they can spread throughout the
host (Wastling et al. 1993). In the pregnant animal, the
tachyzoites invade and multiply within the caruncular
septa in the placentome and then go on and invade the
adjacent foetal trophoblast cells where they can spread
to the rest of the foetus (Buxton & Finlayson 1986). If in-
fection of the foetus occurs early in gestation, while the
foetal immune system is still relatively immature foetal
death is the usual outcome, whereas infection later in
gestation may result in the lamb being born live, but in-
fected and immune. A Toxoplasma infection occurring
at mid-gestation typically results in a stillborn or weak
lamb accompanied by a small mummified foetus. Char-
acteristic lesions on the infected placenta are white spots
visible to the naked eye due to areas of necrosis resulting
in the impaired function of the placenta (Buxton & Rod-
ger 2008). The natural immunomodulation, that occurs
during pregnancy in the ewe acts to damp down inflam-
matory Th1-type immune responses within the placenta
(Entrican 2002, Innes & Vermeulen 2006), as a result
placental tissue is particularly vulnerable to invasion
and establishment of T. gondii tachyzoites. Following in-
vasion of the host by the parasite the innate and adaptive
immune responses are activated and act together to limit
tachyzoite multiplication (Innes & Vermeulen 2006).
Studies in sheep looking at the kinetics of develop-
ment of in-vivo immune responses during a primary in-
fection with T. gondii has shown the early induction of
interferon gamma (IFNγ) within 48 h (Innes et al. 1995b).
This early induction of IFNγ may be important in limit-
ing intracellular multiplication of the parasite (Oura et
al. 1993) and may also help to create an appropriate cy-
tokine microenvironment to induce a Th-1 type adaptive
immune response (Gazzinelli et al. 1996). A phenotypic
analysis of the lymphoblast cells responding to a primary
T. gondii infection in sheep showed an initial predomi-
nance of CD4+ T-cells (Innes et al. 1995a). Around day
10 post-infection, when the peak lymphoblast response
was observed, there was a switch to CD8+ T-cells be-
ing the dominant cell population. In vitro studies showed
that these activated CD8+ T-cells were able to inhibit
intracellular multiplication of tachyzoites (Innes et al.
1995a) and following the peak lymphoblast response in
efferent lymph draining the site of infection the parasites
were no longer detected within the lymph samples (Innes
& Wastling 1995). Specific antibodies to T. gondii were
detected from day 10-12 after the initial infection (Innes
& Wastling 1995). Therefore it would appear that cell-
mediated immune responses involving IFNγ, CD4+ and
CD8+T-cells are involved in protective immunity and re-
covery from a primary infection, while specific antibody
may be more important in defending the host following a
secondary challenge (Innes & Vermeulen 2006).
Following a primary infection with T. gondii, most
sheep develop protective immunity against further dis-
ease therefore controlling the disease using vaccination
may be a feasible goal. Current knowledge of protective
immunity would suggest that an effective vaccine would
have to stimulate cell-mediated immune responses. At-
tempting to induce such responses with different vac-
cine preparations would require an awareness of the role
of regulatory cytokines in balancing and controlling the
potential immunopathology caused by a vigorous inflam-
matory response at the materno-foetal interface (Innes &
Vermeulen 2006, Pfaff et al. 2007). Another challenge
would be to devise methods of antigen delivery that would
allow the processing and presentation of antigens within
the correct MHC background in order to effectively stimu-
late the required T-cell responses. This is easier to achieve
using a live vaccine preparation and may help to explain
the success of the S48 strain vaccine used successfully to
protect sheep and goats against congenital toxoplasmosis
(O’Connell et al. 1988, Buxton & Innes 1995).
S48 strain Toxovax® vaccine
The S48 strain was originally isolated from an abort-
ed lamb in New Zealand and was maintained in the labo-
ratory by repeated passage in mice. Researchers then ob-
served that the parasites had over time lost the ability to
differentiate into bradyzoites or oocysts and had become
effectively an incomplete strain (O’Connell et al. 1988).
The S48 strain tachyzoites induce a short-lived infec-
tion in sheep of around 14 days before being eliminated
Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 104(2), March 2009
from the host by the sheep’s immune system (Innes &
Wastling 1995). As this strain has lost the ability to dif-
ferentiate into bradyzoites, it is not able to establish a
persistent infection in the animal (Buxton 1993). It is
also unable to initiate the sexual life cycle in cats and
cannot lead to the production of oocysts. The S48 strain
tachyzoites are able to undergo limited multiplication
within the sheep, and therefore induce protective cell-
mediated immune responses involving CD4+, CD8+
T-cells and IFNγ (Innes et al. 1995a). In sheep vacci-
nated with S48 and then challenged with an additional
live infection, the parasite is prevented from spreading
within the lymph system (Buxton et al. 1994). Therefore
when a vaccinated pregnant sheep ingests oocysts on
pasture the released sporozoites will invade the gut wall
and enter the mesenteric lymph node where the immune
system will be primed to limit the spread of the parasite
from the lymph to the circulation of the host. Therefore
the parasite will be prevented from reaching the placenta
and causing disease and in addition there will be little
dissemination of the parasite to other tissues. As a con-
sequence, the vaccine may have the additional benefit
of not only preventing congenital toxoplasmosis, but in
addition reducing the risk of meat from the sheep har-
bouring T. gondii tissue cysts. A further advantage of
this vaccine is that one shot will protect animals against
T. gondii induced abortion for up to at least 18 months
(Buxton et al. 1993). The vaccine is normally adminis-
tered prior to mating and there is a meat and milk with-
drawal period of six weeks following S48 vaccination.
Disadvantages are that as the vaccine is live it has a
relatively short shelf life and care has to be taken with
administration as it is a zoonotic pathogen. Clearly, a
live vaccine would not be appropriate for use in humans
and those working on vaccines targeted for human use
have focussed on identification of immunodominant an-
tigens and effective vaccine delivery systems to induce
the appropriate protective immune responses. These
studies have largely involved the use of mouse models of
congenital infection to test the efficacy of the different
preparations. Pregnant sheep may be a very useful ani-
mal model to test the efficacy of different vaccine prepa-
rations to protect against congenital toxoplasmosis as the
disease in sheep is very similar to that seen in pregnant
women (Innes & Vermeulen 2006).
Vaccines to reduce tissue cysts
A recent European multicentre study indicated that
up to 60% of T. gondii infections may be attributed to
the consumption of undercooked or cured meat prod-
ucts from animals infected with the parasite (Cook et
al. 2000). The numbers of tissue cysts and their location
varies between different meat producing livestock and
the husbandry practices used to rear them. Meat from
pigs, sheep, goats and free range poultry are thought to
be the major sources of human infection (Tenter et al.
2000). Undercooked pork in particular was highlighted
as a major risk to consumers in a study conducted in the
USA looking at the presence of viable T. gondii within
meat samples taken from retail meat stores (Dubey et
al. 2005). Indoor reared pigs and poultry with adequate
measures of hygiene and confinement have led to a de-
crease in the levels of T. gondii infection (Tenter et al.
2000). However, the rise in consumer demand for out-
door reared animal friendly production systems has
led to a higher prevalence of T. gondii in these animals
which may pose an increased risk to people consuming
outdoor reared meat (Kijlstra et al. 2004). Development
of vaccines to prevent or reduce T. gondii tissue cysts in
meat producing animals would be of great benefit in re-
ducing the risk of transmission to people. Animals graz-
ing on pastures such as sheep and goats often show high
seroprevalences in many parts of the world indicating
that there is a high level of environmental contamina-
tion with T. gondii oocysts (Tenter et al. 2000) and tis-
sue cysts are readily found in sheep muscles and tissues
(Esteban et al. 1999).
The potential of the S48 Toxovax® vaccine in reduc-
ing the development of tissue cysts in vaccinated sheep
has been discussed above. A similar type of live vac-
cination approach using the RH strain of T. gondii had
been used to immunise pigs to help prevent the develop-
ment of parasite cysts in their tissues (Dubey et al. 1991).
A further study improved the efficacy of immunisation
with RH strain tachyzoites by using oligodeoxynucle-
otides containing immunostimulatory CpG motifs as
an adjuvant (Kringel et al. 2004). The live vaccination
approach using RH tachyzoites appeared to be more ef-
fective in prevention of T. gondii tissue cyst formation
in pigs compared to a study using a crude fraction of
T. gondii rhoptry proteins incorporated into immunosti-
mulating complexes (Garcia et al. 2005). A recent study
examined whether it was feasible to induce protective
humoral and cell mediated immune responses in pigs
following DNA vaccination (Jongert et al. 2008). Pigs
were immunised intradermally using a GRA1-GRA7
DNA vaccine cocktail which induced strong humoral
and type I cell-mediated immune responses including
IFNγ which is known to be important in inhibiting mul-
tiplication of T. gondii (Oura et al. 1993). These results
were encouraging in the development of vaccines that
may protect against the formation of T. gondii tissue
cysts in meat producing animals.
Vaccines to reduce oocyst shedding
Following a primary infection with T. gondii cats
will shed millions of oocysts in their faeces (Dubey &
Beattie 1988). Following this primary shedding of oo-
cysts, cats do develop some immunity and therefore are
unlikely to shed further oocysts upon re-infection or re-
shed oocysts from the original infection. However this
immunity may not last for the lifetime of the cat and
research has shown that cats may shed further oocysts
when re-challenged around six years after their primary
infection (Dubey 1995). These sporulated oocysts are
major environmental contaminants and are an impor-
tant source of infection for livestock and other animals
including humans. There have been recent reports of
human outbreaks of toxoplasmosis attributed to oocyst
contamination of water supplies in Canada (Bowie et al.
1997) and Brazil (Bahia-Oliveira et al. 2003). In addi-
tion, there have been several reports of T. gondii oocysts
Veterinary vaccines against T. gondii • Elisabeth A Innes et al.
from the environment contaminating oceans and being
a source of fatal infection in marine mammals as these
animals has very little resistance to the parasite (Dubey
et al. 2003, Conrad et al. 2005). A vaccine to help pre-
vent oocyst shedding in cats would be highly desirable
and of significant benefit in limiting the environmental
contamination with the parasite thus reducing infection
in many intermediate hosts.
A promising candidate vaccine in this respect is
T-263 strain of T. gondii (Frenkel et al. 1991). This mutant
strain of T. gondii will only undergo partial development
in the gut of the cat which does not result in production
of oocysts. In addition, cats fed T-263 strain bradyzoites
developed significant immunity against oocyst shedding
following challenge with a complete strain of T. gondii
(Frenkel et al. 1991). A further study showed improved
efficacy of the vaccine when intact tissue cysts and re-
leased bradyzoites were administered in two oral doses
to a group of cats (Freyre et al. 1993). The cats in this
study were challenged 47 days later using a complete
strain of T. gondii, T-265 and no oocyst shedding was
detected in the cats after challenge (Freyre et al. 1993).
The potential of this vaccine in the field was tested in
a large scale trial conducted on young cats caught and
trapped on eight commercial pig farms in the USA. The
cats were vaccinated with the T-263 vaccine and the ef-
ficacy of the vaccine was measured indirectly by exam-
ining seroprevalence of other intermediate animal hosts,
including the farmed pigs within the study farms (Ma-
teus-Pinilla et al. 1999). The results showed a decrease in
seroprevalence within the pig population implying that
vaccinating the cats had reduced the shedding of T. gon-
dii oocysts into the environment and therefore reduced
the source of infectious material for the intermediate
animal hosts in this area (Mateus-Pinilla et al. 1999).
Further analysis of this study showed that the decrease
in T. gondii seroprevalence observed in the farm pigs
was related to the number of cats on the farm, oocyst
survival in the environment and the vaccination of cats
with the T-263 vaccine (Mateus-Pinilla et al. 2002).
The T-263 mutant strain has proved to have good ef-
ficacy in vivo, although a disadvantage for large scale
production of the vaccine is that it is produced by infect-
ing mice and the T. gondii cysts are harvested from the
mouse brains. The vaccine is administered live therefore
has a limited shelf life and may be hazardous to those
administering it. The vaccine is kept frozen until de-
livery to try and maintain viability of the bradyzoites
(Choromanski et al. 1995).
Other studies have looked at immunization of cats
using different strains of T. gondii. In one study, kittens
were vaccinated with 60Co irradiated tachyzoites of the
Beverley strain of T. gondii which afforded partial pro-
tection against oocyst shedding when the kittens were
challenged with T. gondii cysts from the Beverley strain
(Omata et al. 1996). In the same study kittens vaccinat-
ed with 60Co irradiated or fixed tachyzoites of the RH
strain, shed oocysts when challenged with the Beverly
strain implying that development of protective immunity
using the Beverley strain of T. gondii seemed to be spe-
cific to the immunising strain (Omata et al. 1996). In a
further study, eight out of nine cats inoculated with ME-
49 strain of T. gondii were protected against oocyst shed-
ding following challenge with three different strains of
Toxoplasma, showing that the ME-49 strain was capable
of inducing well cross protective immunity (Freyre et
al. 2007). The ROP2 antigen of T. gondii has been tested
as a vaccine in cats using a recombinant feline herpes-
virus type 1 vector to deliver the antigen, resulting in
reduced numbers of cerebral parasites (Mishima et al.
2002). Most of the studies involving vaccination against
T. gondii in cats have involved live vaccine preparations
as it is likely that these will induce appropriate protec-
tive cell-mediated immune responses, however they do
have drawbacks in terms of safety, large scale produc-
tion and short shelf life.
Toxoplasma is a highly successful parasitic organism
that is able to infect and live within a very wide range
of different animal hosts. Improved understanding of
disease pathogenesis within different host species along
with knowledge of the parasite lifecycle and transmis-
sion routes has allowed more specific targeting of con-
trol and intervention strategies. Vaccination is an attrac-
tive option to control disease and to limit spread of the
parasite both within the host and into the environment
as most animals develop protective immune responses
following primary infection with T. gondii. As T. gondii
is an obligate intracellular parasite, cell-mediated im-
mune responses involving both the innate and adaptive
immune responses such as NK cells, CD4+ and CD8+
T-cells and both pro-inflammatory and regulatory cy-
tokines are known to be important in protecting the host
and limiting multiplication of the parasite. It is consi-
derably easier to stimulate appropriate cell-mediated im-
mune responses through live vaccine preparations as the
relevant antigens are processed and presented to the host
in a similar way to natural infection. This may explain
why many of the successful veterinary vaccines to date
are using live attenuated strains of the parasite that will
undergo limited multiplication within the host, but not
cause disease or persistent infection. However, live vac-
cines have drawbacks in that they can be problematic to
produce in large quantities, they may be unstable, have
a short shelf life and there are safety concerns due to the
zoonotic nature of the parasite. In addition, live vaccines
would not be considered safe to use in people. Therefore,
the focus of current research is to identify the main pro-
tective antigens within the different life cycle stages of
T. gondii and use novel antigen delivery systems to try
and stimulate protective cell-mediated immune respons-
es. Animal models of toxoplasmosis are very important
to help us to generate the technology required to develop
safe and effective vaccines against toxoplasmosis that
could be used in humans.
Bahia-Oliveira LM, Jones JL, Zevedo-Silva J, Alves CC, Orefice F,
Addiss DG 2003. Highly endemic, waterborne toxoplasmosis in
North Rio de Janeiro state, Brazil. Emerg Infect Dis 9: 55-62.
Blewett DA, Miller JK, Buxton D 1982. Response of immune and
susceptible ewes to infection with Toxoplasma gondii. Vet Rec
Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 104(2), March 2009
Blewett DA, Trees AJ 1987. The epidemiology of ovine toxoplasmosis
with especial respect to control. Br Vet J Mar 143: 128-135.
Bowie WR, King AS, Werker DH, Isaac-Renton JL, Bell A, Eng SB,
Marion SA 1997. Outbreak of toxoplasmosis associated with mu-
nicipal drinking water. Lancet 350: 173-177.
Buxton D 1993. Toxoplasmosis: the first commercial vaccine. Para-
sitol Today 9: 335-337.
Buxton D 1998. Protozoan infections (Toxoplasma gondii, Neospora
caninum and Sarcocystis spp.) in sheep and goats: recent advances.
Vet Res 29: 289-310.
Buxton D, Finlayson J 1986. Experimental infection of pregnant sheep
with Toxoplasma gondii: pathological and immunological obser-
vations on the placenta and foetus. J Comp Pathol 96: 319-333.
Buxton D, Innes EA 1995. A commercial vaccine for ovine toxoplas-
mosis. Parasitol 110 (Suppl.): S11-S16.
Buxton D, Rodger SM 2008. Toxoplasmosis and neosporosis. In
Diseases of sheep. 4th ed (Aitken ID ed) Wiley-Blackwell,
Hoboken, p. 112-118.
Buxton D, Thomson KM, Maley S, Wastling JM, Innes EA, Pan-
ton WRM 1994. Primary and secondary responses of the ovine
lymph node to Toxoplasma gondii: cell output in efferent lymph
and parasite detection. J Comp Pathol 111: 231-241.
Buxton D, Thomson KM, Maley S, Wright S, Bos HJ 1993. Experi-
mental challenge of sheep 18 months after vaccination with a live
(S48) Toxoplasma gondii vaccine. Vet Rec 133: 310-312.
Choromanski L, Freyre A, Popiel R, Brown K, Grieve R, Shibley G
1995. Safety and efficacy of modified live feline Toxoplasma
gondii vaccine. Dev Biol Stand 84: 269-281.
Conrad PA, Miller MA, Kreuder C, James ER, Mazet J, Dabritz H,
Jessup DA, Gulland F, Grigg ME 2005. Transmission of Toxo-
plasma: clues from the study of sea otters as sentinels of Toxo-
plasma gondii flow into the marine environment. Int J Parasitol
Cook AJ, Gilbert RE, Buffolano W, Zufferey J, Petersen E, Jenum PA,
Foulon W, Semprini AE, Dunn DT 2000. Sources of Toxoplasma
infection in pregnant women: European multi centre case-control
study. European Research Network on Congenital Toxoplasmo-
sis. BMJ 15: 142-147.
Dubey JP 1984. Experimental toxoplasmosis in sheep fed Toxoplasma
gondii oocysts. Int Goat Sheep Res 2: 93-104.
Dubey JP 1995. Duration of immunity to shedding of Toxoplasma
gondii oocysts by cats. J Parasitol 81: 410-415.
Dubey JP, Beattie CP 1988. Toxoplasmosis of animals and man, Boca
Raton, Florida, 220 pp.
Dubey JP, Hill DE, Jones JL, Hightower AW, Kirkland E, Roberts
JM, Marcet PL, Lehmann T, Vianna MCB, Sreekumar C, Kwok
OCH, Gamble HR 2005. Prevalence of viable Toxoplasma gondii
in beef, chicken and pork from retail meat stores in the United
States: risk assessment to consumers. J Parasitol 91: 1082-1093.
Dubey JP, Urban JF Jr, Davis SW 1991. Protective immunity to toxo-
plasmosis in pigs vaccinated with a nonpersistent strain of Toxo-
plasma gondii. Am J Vet Res 52: 1316-1319.
Dubey JP, Zarnke R, Thomas NJ, Wong SK, Van Bonn W, Briggs M,
Davis JW, Ewing R, Mensea M, Kwok OCH, Romand S, Thulliez
P 2003. Toxoplasma gondii, Neospora caninum, Sarcocystis neu-
rona and Sarcocystis canis-like infections in marine mammals.
Vet Parasitol 116: 275-296.
Duncanson P, Terry RS, Smith JE, Hide G 2001. High levels of con-
genital transmission of Toxoplasma gondii in a commercial sheep
flock. Int J Parasitol 31: 1699-1703.
Entrican E 2002. Immune regulation during pregnancy and host-patho-
gen interactions in infectious abortion. J Comp Pathol 126: 79-94.
Esteban-Redondo I, Maley SW, Thomson K, Nicoll S, Wright S, Bux-
ton D, Innes EA 1999. Detection of T. gondii in tissues of sheep
and cattle following oral infection. Vet Parasitol 86: 155-171.
Faull WB, Clarkson MJ, Winter AC 1986. Toxoplasmosis in a flock
of sheep: some investigations into its source and control. Vet Rec
Ferguson DJ, Hutchison WM, Dunachie JF, Sim JC 1974. Ultrastruc-
tural study of early stages of asexual multiplication and micro-
gametogony of Toxoplasma gondii in the small intestine of the cat.
Acta Pathol Microbiol Scand Microbiol Immunol 82: 167-181.
Frenkel JK, Dubey JP, Miller NL 1970. Toxoplasma gondii in cats: fae-
cal stages identified as coccidian oocysts. Science 167: 893-896.
Frenkel JK, Pfefferkorn ER, Smith DD, Fishback JL 1991. Prospec-
tive vaccine prepared from a new mutant of Toxoplasma gondii
for use in cats. Am J Vet Res 52: 759-763.
Freyre A, Choromanski L, Fishback JL, Popiel I 1993. Immunisation
of cats with tissue cysts, bradyzoites and tachyzoites of the T-263
strain of Toxoplasma gondii. J Parasitol 79: 716-719.
Freyre A, Falcon J, Mendez J, Gastell T, Venzal JM 2007. Toxoplas-
ma gondii cross-immunity against the enteric cycle. J Parasitol
Garcia JL, Gennari SM, Navarro IT, Machado RZ, Sinhorini IL,
Freire RL, Marana ER, Tsutsui V, Contente AP, Begale LP 2005.
Partial protection against tissue cyst formation in pigs vaccinated
with crude rhoptery proteins of Toxoplasma gondii. Vet Parasitol
Gazzinelli RT, Amichay D, Sharton-Kersten T, Grunwald E, Farber
JM, Sher A 1996. Role of macrophage-derived cytokines in the
induction and regulation of cell-mediated immunity to Toxoplas-
ma gondii. In U Gross (ed.). Toxoplasma gondii, Springer-Verlag,
Heidelberg, p. 127-139.
Hartley WJ, Jebson JL, McFarlane D 1954. New Zealand type II abor-
tions in ewes. Aust Vet J 30: 216-218.
Hartley WJ, Marshall SC 1957. Toxoplasmosis as a cause of ovine
perinatal mortality. N Z Vet J 5: 119-124.
Hartley WJ, Moyle GG 1982. Further observations on the epidemi-
ology of ovine Toxoplasma infection. Aust J Exp Biol Med Sci
Hutchison WM 1965. Experimental transmission of Toxoplasma gon-
dii. Nature 206: 961-962.
Hutchison WM, Dunachie JF, Sim JC, Work K 1970. Coccidian-like
nature of Toxoplasma gondii. Br Med J 1: 142-144.
Innes EA 1997. Toxoplasmosis: comparative species susceptibility
and host immune response. Comp Immunol Microbiol Infect Dis
Innes EA, Panton WR, Sanderson A, Thomson KM, Wastling JM,
Maley SW, Buxton D 1995a. Induction of CD4+ and CD8+ T cell
responses in efferent lymph responding to Toxoplasma gondii in-
fection: analysis of phenotype and function. Parasite Immunol
Innes EA, Panton WR, Thomson KM, Maley S, Buxton D 1995b. Ki-
netics of interferon gamma production in vivo during infection
with the S48 vaccine strain of Toxoplasma gondii. J Comp Pathol
Innes EA, Vermeulen AN 2006. Vaccination as a control strategy
Veterinary vaccines against T. gondii • Elisabeth A Innes et al. Download full-text
against the coccidial parasites Eimeria, Toxoplasma and Neospora.
Parasitol 133: 145-168.
Innes EA, Wastling JM 1995. Analysis of in vivo immune responses
during Toxoplasma gondii infection using the technique of lym-
phatic cannulation. Parasitol Today 11: 268-271.
Jongert E, Melkebeek V, De Craeye S, Dewit J, Verhelst D, Cox E 2008.
An enhanced GRA1-GRA7 cocktail DNA vaccine primes anti-
Toxoplasma immune responses in pigs. Vaccine 26: 1025-1031.
Kijlstra A, Eissen OA, Cornelissen J, Munniksma K, Eijck I, Kort-
beek T 2004. Toxoplasma gondii infection in animal-friendly pig
production systems. Invest Ophthalmol Vis Sci 45: 3165-3169.
Kringel H, Dubey JP, Beshah E, Hecker R, Urban JF Jr 2004. CpG-
oligodeoxynucleotides enhance porcine immunity to Toxoplasma
gondii. Vet Parasitol 123: 55-66.
Lingelbach K, Joiner KA 1998. The parasitophorous vacuole mem-
brane surrounding Plasmodium and Toxoplasma: an unusual
compartment in infected cells. J Cell Sci 111: 1467-1475.
Lunden A, Nasholm A, Uggla A 1994. Long-term study of Toxoplas-
ma gondii infection in a Swedish sheep flock. Acta Vet Scand
Mateus-Pinilla NE, Dubey JP, Choromanski L, Weigel RM 1999.
A field trial of the effectiveness of a feline Toxoplasma gondii
vaccine in reducing T. gondii exposure for swine. J Parasitol 85:
Mateus-Pinilla NE, Hannon B, Weigel RM 2002. A computer simu-
lation of the prevention of the transmission of Toxoplasma gon-
dii on swine farms using a feline T.gondii vaccine. Prev Vet Med
McColgan C Buxton D, Blewett D 1988. Titration of Toxoplasma gon-
dii oocysts in non-pregnant sheep and the effects of subsequent
challenge during pregnancy. Vet Rec 123: 467-470.
Mishima M, Xuan X, Yokoyama N, Igarashi I, Fujisaki K, Nagasawa
H, Mikami T 2002. Recombinant feline herpesvirus type I ex-
pressing Toxoplasma gondii ROP2 antigen inducible protective
immunity in cats. Parasitol Res 88: 144-149.
Morley EK, Williams RH, Hughes JM, Terry RS, Duncanson P, Hide
G 2005. Significant familial differences in the frequency of abor-
tion and Toxoplasma gondii infection within a flock of Charollais
sheep. Parasitology 131(Pt. 2): 181-185.
O’Connell E, Wilkins MF, Te Punga WA 1988. Toxoplasmosis in sheep.
II. The ability of a live vaccine to prevent lamb losses after an intra-
venous challenge with Toxoplasma gondii. N Z Vet J 36: 1-4.
Omata Y, Aihara Y, Kanda M, Saito A, Igarashi I, Suzuki N 1996.
Toxoplasma gondii experimental infection in cats vaccinated
with 60 Co-irradiated tachyzoites. Vet Parasitol 65: 173-183.
Oura CA, Innes EA, Wastling JM, Entrican G, Panton WR 1993. The
inhibitory effect of ovine recombinant interferon-gamma on in-
tracellular replication of Toxoplasma gondii. Parasite Immunol
Pfaff AW, Abou-Bacar A, Letscher-Bru V, Villard O, Senegas A, Mous-
li M, Candolfi E 2007. Cellular and molecular physiopathology
of congenital toxoplasmosis: the dual role of IFNγ. Parasitol 134:
Plant JW, Richardson N, Moyle GG 1974. Toxoplasma infection and
abortion in sheep associated with feeding of grain contaminated
with cat faeces. Aust Vet J 50: 19-21.
Rodger SM, Maley SW, Wright SE, Mackellar A, Wesley F, Sales J,
Buxton D 2006. Ovine toxoplasmosis; the role of endogenous
transmission. Vet Rec 159: 768-772.
Tenter AM, Heckeroth AR, Weiss LM 2000. Toxoplasma gondii: from
animals to humans. Int J Parasitol 30: 1217-1258.
Waldeland H 1977. Toxoplasmosis in sheep. Influence of various fac-
tors on the antibody contents. Acta Vet Scand 18: 237-247.
Wastling JM, Nicoll S, Buxton D 1993. Comparison of two gene am-
plification methods for the detection of Toxoplasma gondii in ex-
perimentally infected sheep. J Med Microbiol 38: 360-365.
Watson WA, Beverley JKA 1971. Epizootics of toxoplasmosis causing
ovine abortion. Vet Rec 88: 120-124.