Mycotoxins and disruption
of vaccination efficacy

in swine

Vaccination programs in pig farms are a fundamental preventive tool against a wide range of diseases. We explore the impact of mycotoxins on vaccine efficacy with Assistant Professor Panagiotis Tassis.

Assistant Prof. Panagiotis Tassis

Assistant Professor of Swine Medicine and Reproduction, Clinic of Farm Animals, School of Veterinary Medicine, Aristotle University of Thessaloníki, Greece

Pig farm vaccination programs are a major preventive tool for a wide range of diseases and syndromes affecting swine. They have colossal importance in terms of herd health and productivity, as well as from a financial standpoint.

Therefore, proper vaccine selection and proper implementation are the basis for the construction of a herd immune status that will counteract antigenic pressure during different productive stages.

As already discussed in the respective literature, mycotoxins seem to play an important role in disrupting this major preventive health tool1.

In our previous technical article regarding the effects of major mycotoxins on the immune system of swine and cellular and molecular mechanisms involved, it had been reported that the health and economic impact of mycotoxins on the immune defense system of pigs is significant.

Three major outcomes of these effects on the swine immune system, herd health and productivity have been described2:

  • Increased susceptibility to infectious diseases
  • Reactivation of chronic infections
  • Decreased vaccination efficacy

The present article will focus on the main mycotoxins affecting swine and extensively contaminate crops worldwide3.

The current knowledge on the effects of aflatoxins (AFs), fumonisins (FBs and mainly FB1) deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA) and T-2 toxin, on the immune response after sensitization or vaccination in swine will be presented.

Emphasis will be put on studies with pigs and
vaccines against swine pathogens.

Swine vaccines and vaccinal immunity 

The use of veterinary vaccines in swine production is a disease prevention tool that has been used by swine farmers worldwide in a variety of production systems.

It is still implemented in every conventional pig production system. In the past few decades, facts in the field of novel vaccine production have changed rapidly.

The scientific field of swine vaccine development is a rapidly evolving research and innovation field.

Major swine diseases that can be prevented or controlled at field level with the use of commercially available vaccines, as part of a veterinary health management programme, include:

  • Porcine Reproductive and Respiratory Syndrome (PRRS)
  • Porcine Circovirus 2-associated diseases (PCV2-AD)
  • Aujeszky’s disease (PRV)
  • Parvovirus infection (PPV)
  • Swine influenza (SIV)
  • Enzootic pneumonia (Mycoplasma hyopneumoniae)
  • Pleuropneumonia (App – Actinobacillus Pleuropneumoniae)
  • Glasser’s disease (Haemophilus parasuis)
  • Atrophic Rhinitis (Pasteurella multocida ± Bordetella bronchiseptica)
  • Erysipelas (Erysipelothrix rhusiopathiae)
  • Leptospirosis (Leptospira spp.)
  • Escherichia coli infections
  • Clostridium spp. infections
  • Ileitis (Lawsonia intracellularis)
  • Classical Swine Fever
  • Salmonella spp. and others
In cases such as the recently introduced in the European region African Swine Fever, there aren’t any commercial vaccines available so far. However respective research and development efforts are under way4.

Apart from typical intramuscular vaccination against one pathogen, innovations of vaccine technology in the past decades have resulted in the production of intradermal vaccines, intranasal vaccines, as well as vaccines against more than one pathogen, reaching up to three swine pathogens in one vaccine up today.

Swine vaccines are usually either “dead” (inactivated) or “live” (attenuated) and can be used in different production stages in the breeding stock and/or in suckling, weaned or growing pigs, depending on the vaccine, its pathogenic target and suggested administration programme.

Vaccination success will result in a timely and appropriate humoral response to counteract the specific pathogen in the most susceptible population and production stage at an acceptable extent.

Vaccine success includes:

  • Reduction of infected animals and susceptibility to infection against a specific pathogen
  • Reduced animals as pathogen-carriers (reduced pathogen spreading in terms of time and microbial load)
  • Improved herd immunity levels

Vaccine failure is an issue of great concern due to the severe health and productivity impact on farms. Many reasons for such failure have been described so far, including environmental and management reasons, such as:

  • Improper vaccine storage, handling and administration
  • Incorrect timing of vaccination and others.

However, limited attention has been given to the impact of mycotoxin contaminated feed as a reason for vaccine failure under field conditions.

Nevertheless, recent research data demonstrates the ability of a number of mycotoxins to affect vaccine-induced humoral response with significant impact on health and productivity results.

Effects of Trichothecenes on vaccinal immunity


DON immunostimulatory or immunosuppression effects depend on the dose, frequency and duration of exposure5.

It has been suggested that high doses of DON (greater than 10 μM), cause apoptosis of lymphocytes, resulting in immunosuppression, increased susceptibility to infection, reactivation of latent infections and reduced vaccine efficiency6.

According to a previous review7, trichothecenes may generate an “immune evasion” environment that allows pathogens to escape host and vaccine immune defenses.

After DON exposure, inhibition of immune response has been demonstrated after porcine parvovirus vaccination in rats8.

Further three studies using ovalbumin (OVA) immunization suggested that DON affects anti-OVA immunoglobulins response9-11.

1. In the first study (2.2–2.5 mg DON/kg feed, weaned pigs for 9 weeks), DON increased OVA-specific IgA and IgG, whilst a biphasic effect of the toxin on lymphocyte proliferation after antigen stimulation (upregulation on 21st day post-exposure and down-regulation on 35th to 49th day post-exposure) were reported, along with lower expression of both TGF-β and IFN-γ mRNA expression levels9.

2. In a second study, 3.5 times greater levels of anti-OVA IgG titers in comparison to control animals (3.5 mg DON/kg feed for 42 days) two weeks after the first OVA immunization (day 7 of the study) were demonstrated.

3. In the latter study, seven days after a second OVA immunization (day 21 of the study) anti-OVA IgG levels were similar between groups (DON-fed animals vs. control animals).

Anti-OVA IgA levels in that study were similar between the two trial groups up to one week prior to the end of the study period, and then reduced in the DON-treated animals10.

According to a recent study11 in which pigs were immunized with OVA, PRV, swine fever and porcine circoviruses vaccines, ingestion of feed contaminated with 1.0 and 3.0 mg DON /kg feed reduced the concentration of serum porcine circoviruses antibody titer in pigs, whereas serum OVA antibody titer levels were not affected.

Nevertheless, it should be mentioned that inhibition of IFN-γ (as suggested previously9) and Toll-like Receptors (TLR) expression, assists pathogens escaping host and vaccine immune defenses12.

In a 28-day feeding study with 0.15, or 1.5, or 3 mg DON/kg feed13 and subsequent immunization with sheep red blood cells, delayed peak titers were observed (one week later) in DON-fed animals, when compared with control animals.

Moreover, after feeding 1.8 or 4.7 mg DON/kg feed (pigs over 25.3 kg body weight at the start of the trial) a significant dose-dependent reduction in secondary antibody response to tetanus toxoid was present when compared to the control group14.

Furthermore, after feeding a mixture of 1.0 mg DON /kg and 250μg ZEN/kg contaminated feed and PRV double vaccination, PRV antibody titers were significantly decreased 14 days after booster vaccination15.

Quite similarly in the study of Gutzwiller et al.16, pigs were fed 3.2 mg DON and 0.06 mg ZEN, or 2.1 mg DON and 0.25 mg ZEN/ kg diet and received PPV vaccination (one-tenth of the recommended dose).

In that study mycotoxin exposure did not affect antibody production, probably due to administration of low vaccine dose and the short time interval between vaccination and antibodies determination.


According to a series of studies on the effects of DON on the immune response against PRRS and PCV2 viruses, very interesting findings have been presented17-20.

Major findings included that ingestion of DON contaminated feed can decrease the immune response against PRRSV and influence the course of PRRSV infection in pigs.

In the study of Savard et al.17, piglets received DON- naturally contaminated diets (2.5 and 3.5 mg/kg) and were then inoculated with PRRSV.

In vivo effects of DON ingestion supported a negative effect of the toxin on PRRSV-specific humoral responses (DON at 2.5 mg/kg significantly decreased PRRSV specific humoral responses), as well as amplification of PRRSVattributed negative effects such as those on weight gain, lung lesions, and mortality.

However, such an effect did not associate with a significant increase in viral replication, since DON ingestion resulted in a decrease of PPRSV replication.

In an in vitro study (permissive cells infected with PRRSV were treated with 140–280 ng/ml DON) by the same research group18, a similar observation was reported i.e. replication of PRRSV was significantly inhibited.

In the latter study it was demonstrated that the reduction of viral replication could be attributed to a DON-induced pro-inflammatory cytokine environment that promoted activation of apoptosis, which is an important host defense mechanism, as it interrupts viral replication and eliminates virus-infected cells12,21.

Furthermore, it has been proved that DON can decrease the replication of the attenuated PRRSV vaccine strain in vaccinated pigs and their antibody response to the vaccine19.

Such significant finding is consistent with results from a study with DON-exposed mice vaccinated with inactivated PPV, which demonstrated disruption of the immune response to the vaccine through modulation of specific cytokines and chemokines22.

Moreover, in another study with pigs, DON increased the severity of the viral infection in the presence of porcine circovirus type 2 (PCV2) virus20.

Results showed that viremia and lung viral load tended to be higher in animals ingesting DON contaminated diet at 2.5 mg/kg (pigs were inoculated with PCV2b virus).

However, DON had no significant effect on clinical manifestation of PCV2-AD.

Authors of the latter study supported that DON has neither in vitro nor in vivo clear potentiating effects in the development of PCV2 infection despite slight increases in viral replication.

Nevertheless, it can be concluded that DON exposure may hamper the acquisition of vaccine-induced protective immune responses.


T-2 toxin is reported to be immunotoxic, through its cytotoxic, apoptotic or immunosuppressive attributes23.

A study with necrotic enteritis B (NEB) vaccination of pigs that received 5 mg T-2/kg feed, resulted in significantly reduced NEB antibody levels in T-2-exposed animals24.

Immunosuppression due to T-2 has been also observed in another feeding study with pigs, (0.5-3.0 mg T-2/kg feed), in which animals were immunized with horse globulin.

Results suggested reduction of anti-horse globulin antibodies synthesis, whereas a dose dependent depletion of lymphoid elements in the thymus and spleen, was also reported25.

After OVA immunization, subclinical doses of T-2 toxin induced an early and transient increase of total IgA plasma concentration but a decrease in the anti-OVA IgG titer.

Pigs fed 1.324 or 2.102 mg T-2 toxin/kg exhibited reduced anti-OVA antibody production on day 21 without significant alteration to specific lymphocyte proliferation26.

Effects of Fumonisins on vaccinal immunity

FBs competitively inhibit ceramide synthases (CerS), a group of key enzymes in the biosynthesis of ceramide and more complex sphingolipids, resulting in the disruption of sphingolipid metabolism, whilst they have been also linked with impairment of innate and acquired immune response, including reduction of specific antibody response during vaccination27,28.

Previous studies have supported that FB1 modifies the Th1/Th2 (T-helper 1/T-helper 2) cytokine balance in pigs similar to an impaired humoral response27,29.

In vivo exposure (28 days) of weanling piglets to feed contaminated with 8 mg FB1/kg significantly decreased the expression of IL-4 mRNA (IL-4 is a Th2 cytokine involved in the humoral response) by porcine whole blood cells and diminished the specific antibody titer after vaccination against Mycoplasma agalactiae27.


In a quite similar study with FB1 (8mg FB1/kg feed), significantly decreased specific antibody levels after vaccination against Mycoplasma agalactiae, as well as the mRNA expression level of IL-10 were observed in a sex-related manner, thus proving the immunosuppressive effects of the toxin.

Such differences in the specific immune response were observed only in male pigs, but not female ones29.


In a study by Grenier et al.30, los cerdos recibieron una dieta contaminada con DON (3 mg/kg) o FB (6 mg/kg) o ambas toxinas y fueron inmunizados dos veces con OVA.

Ingestion of diets contaminated with DON or FB individually or in combination altered immunoglobulins production after OVA immunization and reduced anti-OVA IgG plasma concentration.

Alterations were statistically significant for animals receiving FB-contaminated feed, and more pronounced in animals that received the combined mycotoxins-contaminated diet.

An increase of specific IgA was reported for animals receiving DON contaminated diet, but not for those that received combined DON and FB, possibly due to FB interference at the intestinal level through its action on sphingolipids.

At the same time, reduced lymphocyte proliferation upon OVA stimulation was demonstrated in the animals receiving any of the three contaminated diets (DON, FB, or combined DON and FB).

The humoral immune response was significantly disturbed, with a strong decrease in antibodies levels at days 21 and 35 after vaccination, in pigs exposed to 0.5 mg OTA/kg feed and/or 10 mg FB1/kg feed for three months, and vaccinated against Aujeszky’s disease (Suid Herpesvirus 1 [SuHV1])31.

That antibody disruption was detected in animals fed both mycotoxins, either alone or in combination.

In another study with piglets that were orally exposed to a low dose of FB1 (1 mg FB1/kg body weight) for 10 days, a longer shedding of F4(+) enterotoxigenic Escherichia coli (ETEC) following infection and lower induction of the antigen-specific immune response following oral immunization, were presented32.

Both, F4-specific IgM and IgA antibody secreting cells were reduced after FB1-exposure and the authors suggested that FB1 could interfere with the induction phase of the immune response through reduction of in vivo antigen presenting cells maturation.

On the other hand, few particular studies have shown the absence of
FB-attributed significant effects on immune response after vaccination.

Exposure of piglets to FB1-contaminated feed for up to 4 months (1, 5, and 10 mg FB1/kg feed) did not affect significantly their antibody titers against Aujeszky’s disease33.

Quite similarly, pigs fed low levels of FB-contaminated feed (2 mg FB1/kg contaminated culture material/day for 5 weeks) and vaccinated with PRV vaccine showed absence of an FB-attributed significant effect on PRV antibody titers34.

Nevertheless, the majority of studies and respective findings support that FB1 has immunosuppressive properties, alters the cytokine profile and reduces the specific antibody response built during a vaccination protocol.

Effects of Zearalenone on vaccinal immunity

ZEN has significant estrogenic potency in swine but has also been suggested as an immunotoxic compound35.

Few studies have investigated ZEN effects on humoral immune response after vaccination with a commercial vaccine or other type of immunization in pigs.

Nevertheless, the effect of estrogens on the immune system have received attention due to their immunomodulatory activity on cell-mediated responses and antibody production35.

A study performed with ZEN in rats (mycotoxin administered via gavage at dosages of 0, 1, 5, and 30 mg/kg for 36 days) and subsequent inactivated PPV vaccine administration (intraperitoneally), revealed that ZEN, with or without immune challenge, can decrease immunoglobulins in serum and cytokines in lymphoid organs36.

A study with pigs that received ZEN (dietary levels of 1.1 to 3.2 mg/kg feed for 18 days) and a swine fever live vaccine, demonstrated that specific antibody titers in the group treated with ZEN (2.0 and 3.2 mg/kg) were significantly lower 18 days after immunization in comparison with the control group, in a dose-dependent manner.

Levels of IgM showed a trend of decreasing linearly with increased levels of ZEN, indicating that ZEN (3.2 mg/ kg) inhibited humoral immunity in piglets, whilst it was also suggested that ZEN may affect protein metabolism37.

Additionally, it has been discussed that effects of ZEN on humoral immune response could be related to receptor-specific effects, since ZEN is an agonist toward estrogen receptors α (ERα) and a mixed agonist-antagonist of ERβ, with possible full antagonism of the ERβ expressed in B cells35.

Effects of Aflatoxins on vaccinal immunity

For more than a half-century, the detrimental effects of AFs on vaccinal response have been reported.

It has been shown that AFB1 interferes with the development of acquired immunity in swine following erysipelas vaccination with bacterin preparation (a suspension of killed bacteria) of E. rhusiopathiae and increases the severity of infection with E. rhusiopathiae38.

In a previous study that included ingestion of low doses of AFs (140 and 280 ppb for 4 weeks) a tendency towards reduced immune response against Mycoplasma agalactiae (280-ppb-treated group) was observed39.

Previous studies with pigs treated with AFs showed contradicting results.

Joens et al.40 reported significantly lower hemagglutination titers against Treponema hyodysenteriae (name used at present: Brachyspira hyodysenteriae as swine dysentery causative agent), whilst AF ingestion did not alter humoral response of weanling pigs to sheep red blood cells41 or to Erysipelothrix rhusiopathiae42 in other studies.

Moreover, after immunization of pigs with OVA and concurrent AFB1 exposure (385 μg AFB1/kg feed; 867 μg AFB1/kg feed, or 1807 μg AFB1/kg feed) absence of major effect on humoral immunity (concentrations of total IgA, IgG and IgM and specific anti-OVA IgG), but impaired lymphocyte activation was reported43.

In that later study, authors supported that AFB1 exposure does not result in significan modulation of the humoral immune response, whilst it can induce IgA increase but not at statistically significant levels.

Findings of another investigation in mice44 on the involvement of AFB1 in Swine Influenza Virus (SIV) replication in vitro and in vivo, supported that 10–40μg/kg of AFB1 in vivo promotes SIV replication, inflammation and lung damage by activating TLR4-NFkB signaling.

Effects of Ochratoxin A on vaccinal immunity

OTA has a well-described significant nephrotoxic mode of action in swine, whilst it has been suggested as a compound that can affect immune response in swine.

It has been reported that immunosuppression is the first expressed toxic
effect of OTA that may become evident clinically before nephropathy45.

In a study with 1 OTA/kg feed provided to swine for up to three weeks, animals were immunized against Salmonella choleraesuis haemorrhagic diarrhea45.

Results proved OTA-attributed immunosuppression (reduced mean antibody titer on day 21 post immunization) and delayed response to immunization.

Moreover, increased susceptibility to infectious agents (Brachyspira hyodysenteriae and Campylobacter coli infections) was observed.

As reported in the FB section, alterations in humoral immune response were reported also in an in vivo study with pigs (500 μg OTA/ kg feed for 3 months with or without 10 mg FB1/ kg feed), in which a strong decrease in antibody titer was observed after immunization against Morbus Aujesky (PRV)31.

A possible synergistic action of OTA and FB1 on immunosuppression in pigs could be discussed.

 Remarks and conclusions as regards field conditions

Taken together, a large number of studies have demonstrated the negative effects of the previously mentioned mycotoxins on the humoral response after sensitization or vaccination.

A vast majority of significant mycotoxins for swine have shown potential to induce a clear negative effect on immune response against various swine pathogens after vaccination in pigs.

Taking into account that a farm vaccination programme is of colossal importance in terms of disease prevention, the effects of mycotoxins should be taken into consideration.

However, it is important to remember that, under field conditions, such mycotoxins concurrently contaminate pig feed. Therefore, the immune system of pigs receives pressure from more than one mycotoxin, that could result in various interactions as regards immune response after vaccination.

At the field level, diagnostic investigation of reduced vaccine efficacy cases could include feed mycotoxicological analysis, particularly when reduced vaccine efficacy is correlated with other clinical signs of mycotoxicosis or has occurred at a subsequent time interval after alterations in feed raw materials or feed production.
It should be highlighted that the presence of mycotoxins in the feed may lead to a breakdown in vaccinal immunity and to the occurrence of disease even in properly vaccinated flocks2.


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