factors critical for successful vaccination against classical swine fever in endemic areas
TRANSCRIPT
Review
Factors critical for successful vaccination against classical
swine fever in endemic areas
S. Suradhat a,*, S. Damrongwatanapokin b, R. Thanawongnuwech a
a Faculty of Veterinary Science, Chulalongkorn University, Henri-Dunant Road, Bangkok 10330, Thailandb Virology section, The National Institute of Animal Health (NIAH), Department of Livestock Development, Bangkok 10900, Thailand
Received 31 January 2006; received in revised form 28 August 2006; accepted 4 October 2006
www.elsevier.com/locate/vetmic
Veterinary Microbiology 119 (2007) 1–9
Abstract
Classical swine fever (CSF) or hog cholera, caused by the classical swine fever virus (CSFV), is one of the most important
viral diseases that cause serious economic loss to the swine industry worldwide. During the past 5 years, several techniques for
measuring porcine cell-mediated immunity (CMI) were applied, in conjunction with other conventional techniques, to study
factors that influence the induction of CSFV-specific immunity. Information, obtained from a series of experiments,
demonstrated cell-mediated immune responses in providing protective immunity against CSF infection. Although it has been
confirmed that commercially available modified live CSF vaccines are able to induce complete protection in vaccinated pigs,
several factors including maternal immunity, the age of primary vaccination, vaccination protocol and complications caused by
other pathogens, can greatly affect the effectiveness of CSF vaccines in the field.
# 2006 Elsevier B.V. All rights reserved.
Keywords: Classical swine fever; Vaccination; Immunity; Modified live vaccine
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Immunological mechanisms underlying vaccine-induced protective immunity . . . . . . . . . . . . . . . . . . . . . . . . . 2
3. Factors critical for successful vaccination against classical swine fever in endemic areas . . . . . . . . . . . . . . . . . 4
3.1. The vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.2. The pigs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.3. Complications by other pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
4. Final remark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
* Corresponding author at: Faculty of Veterinary Science, Chulalongkorn University, Henri-Dunant Rd., Pathumwan, Bangkok 10330, Thailand.
Tel.: +66 2 218 9583; fax: +66 2 251 1656.
E-mail address: [email protected] (S. Suradhat).
0378-1135/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.vetmic.2006.10.003
S. Suradhat et al. / Veterinary Microbiology 119 (2007) 1–92
1. Introduction
Classical swine fever (CSF), formerly known as
hog cholera, is one of the major diseases, causing
serious economic loss to the swine industry worldwide
(Moennig, 2000). The disease is caused by a Pestivirus
named classical swine fever virus (CSFV), an
enveloped, single-stranded RNA virus (Moennig,
2000). Classical swine fever virus can be classified
genetically into three genogroups (Paton et al., 2000).
All the genogroups have been isolated in Thailand,
with the major prevalence being genogroups 1 and 3
(Parchariyanon et al., 2000). However, during the last
decade, there has been an increased incidence of
subacute and chronic CSF outbreaks caused by the
moderately virulent CSFV, genogroup 2.2. The CSFV
genogroup 2.2 is closely related to the European
CSFVand was first isolated in Thailand in 1996. Since
then, this genogroup has contributed to over 50% of
the isolates during the 1990s (Parchariyanon et al.,
1999). This newly emerged genogroup has become the
major strain circulated in the area, causing milder
clinical symptoms ranging from subacute to chronic
forms of CSF (Parchariyanon et al., 1999; Damrong-
watanapokin et al., 2002).
In the highly endemic areas routine vaccination
against CSF is the most common means used for
prevention and control. However, the increased
incidence of subacute CSF during the 1990s in
Thailand raised several concerns whether the vaccines
and the vaccination programs were still effective.
Since the year 2000, our group has carried out a
research program, conducting several challenge
studies to assess the efficacy of commercially
available CSF vaccines and to evaluate the factors
critical for successful vaccination against CSF. In this
article, the immunological mechanisms involved in
vaccine-induced disease protection and factors related
to successful vaccination against CSF will be further
discussed.
2. Immunological mechanisms underlying
vaccine-induced protective immunity
Most of the information regarding the immunolo-
gical mechanisms involved in protection against
CSFV infection were derived from an experiment
using the modified live, Chinese (C) strain vaccine.
The C strain vaccine is generally accepted to be very
safe in pigs of all age groups, providing complete
protection, i.e. sterile immunity in vaccinated pigs.
The C strain vaccine usually induces detectable
neutralizing antibodies in vaccinated pigs 2–3 weeks
following primary vaccination (Precausta et al., 1983;
Terpstra et al., 1990). However, pigs vaccinated with
the C-strain vaccine appear to be completely protected
against virulent CSFV challenge as early as 1 week
following vaccination (reviewed in Van Oirschot,
2003). It should be noted that, in some cases, vaccine-
induced protection was achieved in the absence of
neutralizing antibodies at the time of challenge
(Launais et al., 1978; Rumenapf et al., 1991). These
findings implicate the vital role of cell-mediated
immunity (CMI) in viral protection during the early
phases of immunity.
Cell-mediated immunity (CMI) is known to have
both an effector and a regulatory role on the immune
system and is believed to be essential for immunity
against intracellular pathogens, including viruses
(Janeway et al., 1999). Previous information regarding
the role of CMI in vaccine induced, viral protection in
pigs has been very limited, due to the lack of reagents
and the impracticality of the conventional techniques
for the detection of porcine CMI. Nevertheless, antigen-
specific lymphoproliferative activity was demonstrated
in peripheral blood lymphocytes from vaccinated pigs
that were protected against the CSFV challenge
(Remond et al., 1981). The existence of CSF-cytotoxic
T lymphocytes (CTL) in the peripheral blood mono-
nuclear cells (PBMC), from immunized pigs, has been
demonstrated (Pauly et al., 1995; Armengol et al., 2002;
Piriou et al., 2003). An alternative technique for
assessing CMI is to measure the production of cytokines
that are known to influence or directly relate to cellular
immunity. Among these cytokines, the role of inter-
feron-gamma (IFN-g) for the induction of CMI has
been well characterized. IFN-g has several immunor-
egulatory effects that are involved in the induction of
anti-viral immunity, including the activation of CTL,
natural killer (NK) cells and phagocytes (Janeway et al.,
1999). The measurement of viral-specific IFN-g
production is believed to be a direct reflection of
viral-specific lymphocyte activities (Mateu de Antonio
et al., 1998; Zuckermann et al., 1998). Furthermore,
viral-specific IFN-g production remains detectable for
S. Suradhat et al. / Veterinary Microbiology 119 (2007) 1–9 3
a long period of time, whereas lymphocyte proliferation
tends to diminish due to the decreased ability of T cells
to produce IL-2 (Mateu de Antonio et al., 1998).
Previously, an ELISPOT assay for measuring porcine
IFN-g producing cells was established and used for
determining the number of pseudorabies virus (PRV)-
specific, IFN-g producing cells. Several reports have
shown that the number of viral-specific IFN-g
producing cells is a good indicator of anti-viral
immunity (Mateu de Antonio et al., 1998; Zuckermann
et al., 1998, 1999). Subsequently, an ELISPOTassay for
determining CSFV-specific IFN-g production was
established and has been used for the assessment of
the CSFV-specific cellular immunity by several
research groups (Suradhat et al., 2001; Armengol
et al., 2002; Rau et al., 2006). In our experience, CSFV-
specific IFN-g secreting cells could be detected in the
PBMC from pigs vaccinated with the lapinized C strain
vaccine, as early as 6 days, and lasted for up to 140 days,
following vaccination (Suradhat et al., 2001). Further-
more, disease protection could be demonstrated in pigs
carrying high numbers of CSFV-specific IFN-g cells at
the time of challenge, while neutralizing antibodies
were still undetectable (Suradhat et al., 2001; Suradhat
and Damrongwatanapokin, 2003). These findings
highlight the role of vaccine-induced cellular immunity
in viral protection during the early phases of immunity.
In addition, the role of CMI in protection against CSFV
infection was indicated even in the presence of CSFV-
specific neutralizing antibodies. When the pigs were
challenged 140 days after a single vaccination, good
correlation occurred between the level of protection and
the level of IFN-g production, more than the antibody
titer (Suradhat et al., 2001). Despite the protective role
of the cellular immune response at the time of
challenge, the role of CSFV-specific antibody following
such challenge should not be excluded, since there was
a significant increase in the SN titers of the vaccinated
pigs, but not the control unvaccinated pigs, following
the challenge (Suradhat and Damrongwatanapokin,
2003; Suradhat et al., 2001). Generally, CSFVinfection
causes severe B-cell depletion (Susa et al., 1992),
possibly by the induction of massive lymphocyte
apoptosis (Summerfield et al., 1998). Protected
pigs were probably able to control the establishment
of viral infection, and therefore, B cell function was
not affected. The rapid anamnestic antibody response
following the CSFV challenge was certainly
advantageous in reducing viral spreading in the
protected animals.
Although an ELISPOT assay can be used to
monitor overall IFN-g production in response to
CSFV, the assay cannot differentiate the lymphocyte
subpopulation responsible for cytokine production.
Thus, it was not clear which cellular subpopulation
(helper T cell; Th, CTL, etc.) was responsible for the
cytokine production observed in the previous ELI-
SPOT study. This limitation has been overcome by the
application of flow cytometry to analyze the cellular
markers and the intracellular cytokine production,
simultaneously. Recent studies revealed that PBMC
from pigs vaccinated with the C-strain vaccine
produced IFN-g in response to CSFV and that the
double-positive (DP), CD4+CD8+ population was the
major IFN-g producer (Suradhat et al., 2005). This
finding is in agreement with previous reports
demonstrating that DP cells, which are the memory
Th population, can produce high levels of IFN-g in
response to a recall antigen or polyclonal T cell
activator (Rodriguez-Carreno et al., 2002; Saalmuller
et al., 2002). The finding also implies that the IFN-g
producing cells detected by ELISPOT assay, following
immunization with the C strain vaccine in the previous
study, were indeed reflecting Th activity.
It should also be noted that the number of IFN-g
producing cells, following vaccination, was always
lower than that observed following CSFV challenge
(Suradhat et al., 2005, 2006). This finding is consistent
with an other report that demonstrated that immuniza-
tion with a modified live vaccine induces a lower level
of cell-mediated response than the actual viral infection
(Piriou et al., 2003). Interestingly, the CD4�CD8+
population was found to be the major IFN-g producer,
while there were a significantly less number of IFN-g
producing DP cells in the PBMC of the vaccinated pigs
during the first week following CSFV challenge
(Suradhat et al., 2005). As it has previously been
suggested, porcine memory Th population preferen-
tially homes to the secondary lymphoid organs
(Zuckermann, 1999), thus, the low number of
antigen-specific DP cells may simply reflect the
difference in tissue homing preference among the
lymphocyte subpopulations, during the effector phase
of the immune response. The increased CD8+ activity in
vaccinated pigs following challenge was possibly
vaccine-induced anamnestic response of the CD8+
S. Suradhat et al. / Veterinary Microbiology 119 (2007) 1–94
population. Alternatively, it is also possible that rapid
IFN-g production by CSFV-specific memory Th,
following the challenge, might contribute to the
generation of CTL (Piriou et al., 2003). Nevertheless,
the data suggests that activation of memory CSFV-
specific Th cells and priming of a viral specific
CD4�CD8+ population, possibly CTL, occurred in the
pigs vaccinated with the C strainvaccine. These cellular
activities are likely be one of the protective immune
mechanisms induced by the C strain vaccine, particu-
larly during an early phase of immunity.
When vaccinated pigs were challenged at a later
stage after vaccination, there seemed to be a good
correlation between the presence of neutralizing
antibodies at the time of challenge and viral protection
(Terpstra and Wensvoort, 1988; Suradhat et al., 2001).
It is generally accepted that vaccinated pigs with
active neutralizing antibody titers of �32 were
considered to be protective (Terpstra and Wensvoort,
1988). It should be noted that this assumption was
obtained from experiments using a modified live
vaccine. As the vaccine antigens are able to enter both
the endogenous and exogenous antigen presentation
pathway, this type of vaccine should efficiently
activate both humoral (neutralizing antibody) and
cell-mediated immunity (CTL). In general, active
CSFV-specific antibody production following vacci-
nation, with the C strain vaccine, correlated well with
the levels of IFN-g production (Suradhat et al., 2001).
Therefore, routine monitoring of SN titers, i.e.
seroprofile, can still be used for assessing the
effectiveness of a CSF vaccine program in the field.
In fact, we strongly recommend routine monitoring of
herd immunity to CSFV, in farms situated in a highly
endemic areas.
As suggested above, neutralizing antibodies also
contribute to viral protection, through the reduction of
spreading and shedding of the infectious virions. The
evidence that neutralizing antibodies, alone, could
provide protection has also been reported. Piglets with
exceptionally high levels of maternal derived neu-
tralizing antibodies (>512) are passively protected
against the CSFV challenge (Parchariyanon et al.,
1994). Furthermore, the E2 subunit vaccine, which
mainly activated the CSFV-specific Th population and
the production of neutralizing antibodies, confer
clinical protection against the CSFV challenge (de
Smit et al., 2001; Uttenthal et al., 2001; Dewulf et al.,
2002). However, it should be noted that the informa-
tion regarding the protective values of the E2 subunit
vaccines were rather inconsistent (reviewed in Van
Oirschot, 2003). As viral protection induced by the E2
subunit vaccine is likely to rely on the ability to induce
CSFV-specific neutralizing antibodies (Van Oirschot,
2003), it may take a longer time (at least 2–3 weeks)
following vaccination or more than one vaccination to
obtain complete viral protection. A recent study in
Thailand has shown that at least two vaccinations were
required to induce clinical protection in pigs carrying a
low level of maternal derived antibodies (MDA), at the
time of vaccination. Nevertheless, most of the
protected pigs still developed fever, leucopenia, and
viraemia following the viral challenge (Damrongwa-
tanapokin et al., 2006). The efficacy of the E2 subunit
vaccine for prevention of horizontal and vertical viral
transmission has also been previously placed in doubt
(Dewulf et al., 2002, 2005).
Findings on the efficacy of the E2 subunit vaccine
suggest that nature of an antigen presented to the
immune system (i.e. endogenously or exogenously
produced form) can significantly affect the ability of
the vaccines to induce protective immunity against
CSFV. Generally, exogenous protein antigen does not
efficiently activate CTL activity (Janeway et al.,
1999). It should be noted that CSFV is cell-associated
and a non-cytopathic virus. Replication is restricted in
the cytoplasm of the cell and the virus can spread
directly from the infected cell to adjacent cells (Van
Oirschot, 1999). Thus, inefficient priming of viral-
specific CTL could be one of the explanations for
incomplete viral protection induced by the subunit
vaccine. Interestingly, plasmid encoding E2 protein of
CSFV conferred complete protection in the vacci-
nated-challenged pigs, even in the absence of
neutralizing antibodies at the time of challenge
(Ganges et al., 2005). Together, these findings
emphasize the vital role of cell-mediated immunity
(i.e. viral specific CTL activity) for controlling viral
spreading in the challenged animals.
3. Factors critical for successful vaccinationagainst classical swine fever in endemic areas
During the past years, we have conducted several
CSF vaccine trials and challenge experiments to
S. Suradhat et al. / Veterinary Microbiology 119 (2007) 1–9 5
investigate the factors critical for the induction of
protective immunity against CSFV by modified live
CSF vaccines. Some of the experiments were
performed in order to verify common beliefs among
swine practitioners, or to evaluate the off-labeled
vaccine usage that was once widely practiced in the
country. Several factors critical for a successful CSF
vaccination program will be discussed further as
follows.
3.1. The vaccines
The C strain, modified live vaccine (MLV) has been
regarded as one of the most effective CSF vaccines that
provides complete clinical and virological protection,
i.e. sterile immunity, within a week of vaccination
(Suradhat et al., 2001; Van Oirschot, 2003). It has been
suggested that the C strain CSF-MLV is the vaccine of
choice for an emergency vaccination protocol (Van
Oirschot, 2003). Several strains of commercial CSF-
MLV, mostly derived from genogroup 1, are available in
the market. In our experience, a single vaccination of
the CSF-MLV, including C strain (both lapinized and
tissue culture derived) and GPE- strains, induced
complete protection against CSFV infection as early
as 6 days after vaccination. It should be noted that this
protective effect was observed on the condition that the
pigs had low levels of MDA (�32) at the time of
vaccination (Suradhat et al., 2001; Suradhat and
Damrongwatanapokin, 2003).
Several genogroups of CSFV have recently been
isolated in Thailand (Parchariyanon et al., 2001).
Although it is well accepted that CSF-MLV can
effectively induce complete protection against all of
the CSFV strains, increased prevalence of the newly
emerged genogroups during the last decade has raised
concerns whether the available vaccines can induce
complete protection to every CSFV genogroup found
in Thailand. Our data, together with other reports,
confirm that CSF-MLV can induce complete protec-
tion against all tested CSFV genogroups, including the
newly emerged genogroups 2 and 3 (Parchariyanon
et al., 2001; Suradhat and Damrongwatanapokin,
2003). Thus, the increased prevalence of new
genogroups is unlikely to be due to any inability of
inducing heterotypic protection by CSF-MLV.
Although, CSF-MLV could effectively induce
protective immunity in pigs, certain conditions are
required to achieve complete viral protection. Off-
labeled vaccine usage, as for example, vaccination of
the CSF vaccine combined in the same injection with
other vaccines should be systemically tested prior to
implementation. In one of our studies, combining the
C-strain vaccine and a live gE-deleted, PRV vaccine
resulted in a significant reduction in cellular response
against CSFV, while there were no differences in the
levels of SN antibody. Although the pigs vaccinated
with the combined vaccine were clinically protected
against CSFV challenge, there were clearly more fever
days and pathological changes in this group, when
compared to those from the pigs vaccinated with the
CSF vaccine alone (Suradhat et al., 2001).
Oral CSF-MLV vaccination was introduced by the
European countries for the purpose of controlling CSF
in wild boars (Van Oirschot, 2003). To obtain
complete protection, the oral CSF vaccine formulation
requires the addition of a vaccine stabilizer and a
higher dose of the MLV virus (Kaden et al., 2000). In
addition, more challenge studies will be needed to
evaluate the effectiveness of this vaccine regimen in
domestic pigs. Vaccine protocols using a commer-
cially available CSF vaccine for oral immunization of
domestic pigs are not, at the moment, recommended.
3.2. The pigs
In our experience, interference by maternal derived
antibodies (MDA) is the most common factor
affecting the induction of protective immunity against
CSFV in the field. Piglets are born agammaglobuli-
naemia and acquire passive immunity by colostral
intake. The levels of CSFV-specific MDA of the
suckling pigs correlate well with the levels of serum
neutralizing (SN) titer of the sows. Without any
exposure to CSFV, MDA gradually declines with a
half-life of approximately 2 weeks (Coggins, 1964).
Generally, it is well accepted that optimal protection
can be achieved by vaccination of piglets carrying
MDA titers of �32 (Suvintrakorn et al., 1993;
Parchariyanon et al., 1994). This can be problematic
in a highly endemic area, where all the pigs are
routinely vaccinated and viral circulation in the farm
can be high. Natural CSFV exposure of the vaccinated
sows leads to anamnestic antibody responses that are
passed on to the piglets without any observed clinical
signs. Although it has been reported that high levels of
S. Suradhat et al. / Veterinary Microbiology 119 (2007) 1–96
MDA can confer some degree of protection, the MDA
titers of more than 256 were required to obtain
complete clinical protection in the piglets (Parchar-
iyanon et al., 1994). Furthermore, it would take a
longer time for the MDA, at this level, to decline to the
level that does not interfere with CSF vaccine efficacy,
i.e. longer window of susceptibility. Accumulating
data indicates that MDA of more than 32 significantly
affects the induction of protective immunity by CSF-
MLV, and this leads to vaccine failure (Suvintrakorn
et al., 1993; Parchariyanon et al., 1994; Suradhat and
Damrongwatanapokin, 2003). In some experiments,
piglets vaccinated in the presence of high MDA titers
never showed seroconversion to the subsequent CSFV
exposure (Parchariyanon et al., 1994; Suradhat and
Damrongwatanapokin, 2003). Interestingly, in the
challenge study using a moderately virulent CSFV
(genogroup 2.2), all challenged pigs survived the
challenge through to the end of the experiment.
However, CSFV could be isolated from the sera of
unvaccinated pigs and 50% of the pigs, vaccinated
while having high levels of MDA. With an increase in
the prevalence of subacute and chronic CSF during the
past years, infected/unprotected pigs may survive for a
long period of time without any obvious clinical signs
of CSF. This clinical situation will certainly compli-
cate any disease control program, as the infected pigs
become an undetected source of infection on the farm.
Again, these findings highlight the significance of
routine serosurveillance and the use of other
diagnostic tools for monitoring the herd immune
status and plans for immunoprophylaxis.
Apart from MDA, the influence of age at the time of
primary vaccination was also investigated. Piglets at
the age range of 3–5 weeks, with comparable levels of
MDA titers (<32), were vaccinated twice at a 2 weeks
interval with the lapinized C strain vaccine. Levels of
CSFV-specific, cellular and antibody responses, were
determined every 2 weeks up to 10 weeks post-
vaccination. The result indicated that piglets immu-
nized at 5 weeks old developed a greater number of
CSFV-specific, IFN-g producing cells in the PBMC
and higher CSFV-specific, SN titers than pigs
immunized at 3 weeks old (Suradhat and Damrong-
watanapokin, 2002). Although CSFV challenge was
not performed in this study, the results clearly
demonstrated that younger pigs are not as immuno-
competent as the older ones. The finding is in
accordance with previous knowledge that the porcine
immune system is fully matured at the age of 4 weeks
(Povey and Carman, 1997). Thus, when emergency
vaccination protocol is implemented in very young
piglets, during an outbreak, a booster vaccination may
be required to achieve complete protection. Further-
more, it is highly recommended that emergency
vaccination protocol should be removed as soon as the
outbreak is over.
3.3. Complications by other pathogens
As shown through our series of experiments, the
induction of protective immunity against CSFV
infection depends on several factors. Most of the
challenge studies were conducted in the isolation units
where disease complications by other pathogens were
minimized. The results and interpretations obtained
from these experiments may underestimate clinical
outcomes in the field, where pigs can be exposed to
several pathogens at the same time. Several pathogens,
mycotoxins and chemicals are known to negatively
modulate the immune system, and therefore, sig-
nificantly interfere with the effectiveness of any CSF
vaccination protocol. In our experience, co-infection
with PRV at the time of CSFV challenge resulted in
fatal CSFV infection of the vaccinated pigs, despite
successful immunization against CSFV, as determined
by the presence of CSFV-specific, IFN-g producing
cells and SN titers, prior to the CSFV challenge (S.
Suradhat, unpublished).
Since its emergence in the late 1980s, porcine
reproductive and respiratory syndrome virus (PRRSV)
has become one of the most economically important
pathogens of the swine industry (Meng, 2000). In
Thailand, the prevalence of PRRSV infection is
believed to be more than 80% (Thanawongnuwech
et al., 2004). Several lines of evidence suggest that
PRRSV can negatively modulate the immune system.
Our recent findings demonstrate that PRRSV induces
systemic production of a very potent immunosup-
pressive cytokine, interleukin-10 (IL-10), during an
early stage of infection (Suradhat and Thanawongnu-
wech, 2003). Furthermore, the presence of PRRSV in
the culture suppressed IFN-g production by the CSF-
MLV primed PBMC when stimulated with the recall
antigen; CSFV (Suradhat et al., 2003). In order to
explore the effect of PRRSV infection on the efficacy
S. Suradhat et al. / Veterinary Microbiology 119 (2007) 1–9 7
of CSF-MLV, we conducted the dual PRRSV-CSFV
challenge experiment. Seventeen days old pigs were
infected with a Thai PRRSV isolate a week before
vaccination with the lapinized C strain vaccine. Three
weeks after CSF vaccination, the pigs were challenged
with the virulent CSFV. The results demonstrated that
PRRSV infection significantly interfered with induc-
tion of CSFV-specific immunity which resulted in
vaccine failure (Suradhat et al., 2006). The finding is
in agreement with a previous report that PRRSV
infection suppresses active antibody responses to CSF
vaccination (Li and Yang, 2003). Interestingly, while
measuring the levels of CSFV-specific, IFN-g
production, we observed that the numbers of IL-10
producing cells by the PBMC from PRRSV infected
pigs were significantly increased during the first 14
days post-infection. The systemic IL-10 production,
occurred at the time of CSF vaccination, was likely to
interfere with CSF vaccine efficacy, and subsequently
led to vaccine failure. We postulated that the PRRSV-
induced, IL-10 production could result in the
inhibition of immune responses to other antigens, to
which they may be exposed during the same period of
PRRSV infection. In fact, the negative effects of
PRRSV infection on the efficacy of other porcine
vaccines have been previously reported by many
investigators (De Bruin et al., 2000; Thacker et al.,
2000). This finding implied that CSF vaccination
during the active stage of PRRSV infection should be
avoided. Taken together, the above findings emphasize
that the influence of other pathogens on the immune
system and/or interactions among the pathogens
should also be taken into consideration. Strict
biosecurity and routine monitoring of the herd
immune status will be crucial for preventing such
complications.
4. Final remark
During the past years, we have explored several
factors critical for successful CSF vaccination in the
field. Our results, together with previous reports,
confirm that CSF-MLV can effectively induce protec-
tive immunity against CSFV infection, when used
properly. In our opinion, CSF vaccine failure that is
observed in the field is primarily due to a lack of
understanding of the herd immune status, mechanisms
of immunological protection, viral pathogenesis, and
epidemiology. Sharing such information among veter-
inary researchers, swine practitioners and farmers,
together with a strengthening of the disease surveillance
program is necessary for a successful CSF preventive
and control program, which in our hope, will eventually
lead to the eradication of CSF in the region.
Acknowledgement
The authors wish to thank Drs. Ratree Platt, Terry
Heard, and Henry Too for helpful comments during
the manuscript preparation.
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