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Is it possible to administer a live PRRS vaccine to animals already infected to stop the piglet’s infection?

Summary: 

Vaccinating the infected sows with a PRRS live vaccine does not seem to help to reduce the clinical signs. It normally reduces the clinical signs in sows when the vaccination is administered before the infection with the field virus. The non-immunised gilts are animals that can help in the replication of the virus on unstable positive farms, and because of this, the vaccination and adaptation before their introduction on the farm is recommended to reduce the clinical signs in these animals and to lower the circulation of the virus on the farm.


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A PRRS outbreak is causing 40% of stillborn piglets. Is it possible to administer a live vaccine to animals already infected to stop the piglet’s infection? Could a vaccine of this kind reduce the number of dead piglets and stop the transmission to new litters?

In this case, an outbreak of stillborn piglets (around 40%) is described, and it is suspected that the cause is PRRS. When we ask for more information on the case, we are told:

Most of the affected litters belong to first parity sows.

No PCR diagnosis of PRSSV on deadborn piglets has been carried out.

Gilts come from another farm, their health status regarding PRRS is unknown, and they are not vaccinated.

The semen used for AI has an external origin.

Vaccinating a newly infected animal with the PRRS field virus does not have practical advantages for the animal, because the immune system already has a strong antigen to process the answer needed. The difficulty does not lie in the individual animal, but on an animal population, because not all the animals become infected at the same time. The PRRS virus is not very contagious, and because of this, the contamination of all the sows on the farm with the field virus will take a long time if we leave the virus to circulate naturally. In these cases, the clinical symptomatology will go on until the last sow becomes immunocompetent against the virus. This can take several months or even years, when negative subpopulations appear on positive farms.

PRRSV-naive gilts are another source of active virus replication when they enter an unstable farm with an active virus circulation. In this case, a situation like the one described can appear. Nevertheless, to be sure, we must diagnose if the PRRSV is the agent responsible for the mortality of the piglets.

If the PRRSV diagnosis is confirmed in the piglets and the gilts that come from an external source, the next step is to reduce the virus circulation on the farm, mainly in the gilts, that may be where the virus proliferates. In cases like this, we recommend vaccinating all the sows to induce some kind of immunisation against the PRRSV and to reduce the clinical symptoms in the sows NOT infected at the time of vaccination. We are not going to avoid the infection of new litters with the field virus, but we can reduce its negative impact and the clinical signs if there is an immunisation previous to the infection.

There is the risk of not achieving enough immunological protection against the field virus with some vaccines, but as of today there is not a technology that allows us to say, with confidence, which is the most effective vaccine for a certain farm. Even after sequencing the virus and choosing the vaccine with the highest homology degree, nothing guarantees us that it will be the most effective one on the farm.

The strategy that we use in clinical outbreaks like this (with a confirmed PRRS diagnosis) is:

The vaccination of all the sows and boars on the farm with a live vaccine on the same day (we will vaccinate the most immunodepressed sows the following week: on the insemination/mating week and the farrowing week). The goal is to obtain a quick immune response against the PRRSV in all the sows in the group, and we expect a certain degree of cross-protection between the vaccine and the field strains. Revaccinate 4 weeks later with the same protocol. 

The gilts that enter the pregnancy stage must be well immunised and non-viraemic (PCR-negative to PRRS and IgG-positive). The vaccination and adaptation of viraemic animals on the farm and allowing enough time in quarantine until they do not excrete the virus (12 weeks is normally enough) are recommended. This is very important for the future control of PRRS on the farm. 

Buying PRRS-negative semen to inseminate the sows. 

Knowing if the virus is circulating in the nurseries. If there is circulation, implement biosecurity rules to reduce the transmission of the virus to the sow herd. 

After the second vaccination of the sows, evaluate if there are still viraemic piglets at birth. If this improves, we can keep the vaccination and adaptation programme only in the gilts in quarantine. 

What is a correct way to choose a PRRS sow vaccination program? When PRRS vaccination of piglets is needed?

Answered by: Enric Marco

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Piglet vaccination is usually done when we would like to reduce PRRS virus circulation on the growing phase. Vaccine will reduce the amount of PRRS virus shed by viremic animals and also will reduce duration of shedding. Those reductions are not spectacular but can help to control the PRRS virus circulation.
Sow PRRS vaccination is used in two ways. The first one is to bring back to normality the farm after an outbreak; the second one is to help the farm to maintain stability by avoiding PRRS virus recirculation among sows which will produce viremic piglets.
By vaccinating sows, immunity will be higher and more stable helping to reduce subpopulations of sows which we know are the responsible for on farm virus recirculation.

Once PRRSV enters your farm, how long does it take to spread to the whole farm? What are the first animals that will show clinical signs?

  
Answer from Dr. Tomasz Stadejek. Warsaw University of Life Sciences. Poland.

The question is very difficult to answer as the outcome of PRRSV infection in a naïve farm is depending on many factors that differ a lot between farms. Some of the factors are:
Type of farm: farrow to finish, farrow to wean or multisite.

Construction of barn compartments.

Pig flow: continuous flow or all in-all out.

Level of internal biosecurity, including personnel flow, disinfection etc.

PRRSV strain characteristics.

In a single site, farrow to finish farm, with continuous flow and low level of internal biosecurity the spread of virus in a population can be rapid. On the other hand, in a multisite farm with high internal and external biosecurity the virus spread can be limited to a single site or barn. The lower level of general farm management, the easier and faster the PRRSV spread.
It has to be remembered that PRRSV strains differ in a level of viremia and shedding by infected pigs. “Milder” viruses will be easier handled by infected animals, the level of shedding can be lower, so the spread of such strain could be slower even in conditions of farrow to finish farm. Recently in Belgium more aggressive PRRSV type 1 strains were described that efficiently replicate in nasal mucosa that helps shedding in aerosols, and in effect, in virus spread.
Clinical symptoms of PRRSV infection can be from very mild to severe, depending on the strain characteristic and existing co-infections in a population, as well as environmental conditions. The earliest symptoms post infection are not specific and most often transient: depression, lethargy and anorexia. Some animals can be feverish and exhibit dyspnea and cough. The better health status of pigs and better environmental conditions, the milder the course of the disease can be. However, there are strains of PRRSV type 1 and particularly of type 2 that can cause high fever and severe pneumonia, even in specific pathogen free pigs. Usually younger pigs are more affected than older pigs, in which the acute phase of infection can be asymptomatic. This phase will start in a part of a farm population where the virus first enters, end eventually the symptoms will roll over the rest of the population, depending on the aforementioned conditions. As the clinical respiratory symptoms are not specific to PRRSV, they can be confused with other disease conditions. Laboratory detection (PCR) of PRRSV in blood, oral fluid or lungs or lymphoid tissue of symptomatic pigs is necessary for early detection of virus infection in a previously naïve farm.
The most prominent clinical symptoms of PRRSV infection is reproductive failure: late term abortion, premature farrowings, stillborn and weakborn piglets and high preweaning mortality. Often this is when PRRSV is first suspected in a farm. It has to be remembered that these symptoms can be caused by PRRSV only if sows or gilts were infected and become viremic in third trimester of gestation. Only then the virus can infect placenta, cause lesions and cross fetal barrier, inducing reproductive failure. Even then not every litter will be affected in the same way. Some litters can be born apparently healthy but infected, and shedding PRRSV to littermates and between litters. Sows that became infected in first half of gestation, control viremia before the virus can cross placenta, so the litters are protected from in utero infection. Such piglets are protected also by colostral antibodies until several weeks of age. Most of cases of reproductive failure have non-infectious etiology so laboratory diagnosis is necessary to confirm the role of PRRSV. Detection of antibodies to PRRSV in sows that, let say, aborted, and virus by PCR in piglets in affected litters confirms PRRS case in a reproductive herd.
As reproductive herd shows delayed effect of PRRSV circulation in a farm, one has to assume that if the reproductive symptoms are evident and confirmed to be linked to PRRSV, the virus must have circulated in a population already for several weeks, unnoticed.
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Effects of PRRS in pigs on a confirmed PRRS positive farm

  
Clinical and productive effects of PRRS in pigs on a positive farm will basically depend on the immunization status of the herd and the virulence of the PRRS virus strain infecting the farm. The immunization status of the herd would depend on the previous PRRS virus circulation on the farm and the vaccination strategies applied.
Once the PRRS virus is introduced into a farm, the circulation of PRRS in pigs of the herd will depend on different factors (Figure 1) such as the production system (i.e: 1-site vs. 2-sites, AIAO vs. continuous flow…), internal biosecurity, replacement gilt management, vaccination and immunization strategies or the presence of subpopulations of negative sows. Generally, it will tend to circulate indefinitely if no control measures are applied and periodical clinical outbreaks can be expected. However, some rare cases of spontaneous elimination of the virus have been described, especially on very small farms:

  
For PRRS infected farms, we can generally distinguish between 3 different situations according to the infecting PRRS virus strain and the previous PRRS status of the farm:

Re-emergence or re-circulation of the same PRRS strain already present on the farm: In this situation, the presence of negative subpopulations can play a crucial role in the clinical presentation and virus circulation. Negative subpopulations can be susceptible to the infection with the PRRS virus present on the farm, experiencing clinical problems and shedding the virus. Since a positive herd population presents homologous immunity against the circulating PRRS, clinical presentations tend to be a temporary mild impairment of productive and reproductive parameters.

Lateral infection introducing a new PRRS virus strain into a positive farm: Depending on the virulence and the immunization level of the herd and the presence of negative subpopulations as well, clinical PRRS problems can range from no effect to a severe outbreak. 

New introduction of the PRRS virus into a negative farm: PRRS infection introduced into a naïve farm will most probably cause serious clinical outbreaks, especially if the PRRS virus strain is highly virulent. Typical reproductive disturbances such as late term abortions and increased numbers of stillborn and weak-born piglets at farrowing. At the same time, increased preweaning mortality can? be observed. Moreover, after this reproductive clinical episode, the PRRS virus will be spread rapidly to weaners and growers.

Brief glossary and background regarding airborne PRRS virus

Airborne Infectious diseases represent a major challenge to human and animal health, mainly due to the difficulty of controlling the air quality within a facility that hosts susceptible individuals.
This challenge is even greater when the cause is an agent like PRRS virus , capable of traveling long distances carried by aerosols. Here are some of the most common terms used when referring to airborne PRRS virus.


Airborne Diseases (AD): Diseases caused by pathogens and transmitted through the air.
Airborne PRRS virus: A systemic swine virus that can be shed in many body secretions and is exhaled in air1.
Airborne Transmission (AT): AT occurs from infected to naïve individuals, when pathogens travel on dust particles or on small respiratory droplets that are stirred up into the expelled air due to coughing, sneezing or exhalation.
Airborne transmission of PRRS virus: American researchers documented for the first time2 the airborne transmission of PRRS virus in 1997. A more recent study suggests that on large sow farms with good biosecurity in swine-dense regions, approximately four-fifths of PRRSV outbreaks may be attributable to aerosol transmission3.
Aerobiology: It is the study of the processes involved in the movement of microorganisms in the atmosphere from one geographical location to another, including the aerosolized transmission of disease. It employs contemporary techniques including computational fluid dynamics to study airborne particle flow, polymerase chain reaction (PCR) methodologies to identify infectious agents and quantify airborne particle concentrations in various settings, and epidemiology to track the spread of disease5.
PRRS aerobiology: Since the late 90s to date, it has been issuing increasingly strong evidence about the role of aerosol transmission of PRRS virus. Recently, the particle concentration, size distribution, and infectivity of PRRS virus emitted by infected pigs, were found associated with a wide range of particle sizes that can deposit throughout the respiratory tract and later be swallowed. PRRS virus viability was particle size dependent with virus isolated only from particles larger than 2.1 µm, supporting the relevance of the aerosol route in the transmission PRRS4.

Air filtration: In human medicine, air filtration is part of the so called -respiratory protection against biologic agents present in bio-aerosols-. These programs include individual and collective protection, mainly in health centers and other places with some risk of airborne diseases.
PRRS virus and air filtration: After several publications on PRRS virus aerosol transmission, not always conclusive or based on partially controlled studies, in 2009 a relevant study using a production region model was published7. It involved a PRRS virus infected population of pigs (source), and two naïve populations of pigs (recipients), housed in separate buildings located 120 meters away. The two recipient barns employed identical biosecurity protocols apart from the installation of bio-aerosol filtration in one barn. Non-filtered populations became infected in 8 of 26 replicates over a one year period, while none of the 26 recipient replicates in filtered barns were infected. It was demonstrated that strict bio-security measures alone were not sufficient at preventing introduction of PRRS virus into the non-filtered populations. For the first time, the effect of bio-aerosol filtration was being studied under semi-controlled conditions5, 6. In this video the principles of air filtration are explained:

Eradication of PRRSv from swine farms. Is it possible?

  
In this post, several experts cover the critical subject of PRRS virus eradication on swine farms. As authorities in their respective fields, they share their experience in preventing the spread of PRRSV within and between farms and the feasibility of eradicating this virus in large swine populations.
Porcine reproductive and respiratory syndrome (PRRS) is an economically significant disease of swine that has been estimated to cost the US and EU industry approximately $664 million a year and €100 per sow. Whilst the industry has made great strides in identifying, characterizing, and diagnosing the PRRS virus in the past few years, unfortunately there is still a lack of adequate knowledge on its epidemiology in swine to allow us to be sure how to proceed with an eradication program once a herd is infected.
We asked several PRRS experts what they think about eradication of PRRSV from swine farms: watch the video.

  

Scott Dee – International Research Veterinarian, Pipestone Veterinary Clinic, USA. 

“I think that’s a very important goal, it’s a long term goal. It’s possible at the individual farm level but it’s very difficult on the regional area level because of the way the virus can be spread. Transmitted through the air for example.”
Carlos Lasagna – Grupo Martini Pig Health Director, Italy.

“When we talk about PRRS eradication I think that is something let’s say possible, not easy but possible. However, what we have to consider in a country like Italy is the possibility that we might get the infection a second time after the eradication.”
Luc Defresne – Seaboard farms Pig Health Director, USA. 

“Eradication always remains the ultimate goal and nobody is against virtue. However, I do not think that right now we have the tools to be able to expand it to a country-wide goal”.
Darwin Reicks – Swine Veterinary Center Minnesota, USA.

“Eradication of PRRS virus has been difficult and, in some cases, also challenging. We feel it is very important when a virus gets into the farm to do an eradication as soon as possible to get back to negative pig flock.”
Albert Rovira – Veterinary Diagnostic Laboratory University of Minnesota, USA.

“We’ve become a lot better in figuring out how to eradicate personal firms and how to keep farms negative from PRRS. Now we have to figure out how to do that for regions and keep moving forward. It might not work for every region and definitely in very dense areas it is a challenge”.
Albert Finestra – Independent Spanish Consultant, Spain: “Thinking about PRRS control on an isolated farm is not difficult. But if you are speaking in a highly populated area like this, it is quite difficult because all neighbours need to work together. Need to vaccinate together, need to implement the same control program. In such a situation, it is not easy to fight against this disease”.
Elisabeth Grosse – Professor, University of Veterinary Medicine Hannover, Germany. “National eradication programs, mandatory for every producer, may be effective but we need to think about the consequences in advance. And to answer those questions we need to realize that the stamping out is the only method, at least today, we have to maintain the farms free from PRRS. We need to clarify whether pig producers as well as society will accept the stamping out policy”.

Cell-mediated immune response in gilts vaccinated with a PRRS vaccine

In an environment poor in neutralising antibodies, cell-mediated response could be used to evaluate immune response after using a PRRS vaccine and more or less effectively predict protection against the virus.
The objective of the following study was to evaluate the cell-mediated response generated in gilts vaccinated with a PRRRS vaccine (UNISTRAIN® PRRS, HIPRA) against different PRRSV strains isolated from clinical outbreaks in the field.
EXPERIMENTAL DESIGN:

The study was conducted in six-months-old gilts, negative for PRRSV, coming from an historically disease-free farm. The animals were distributed between two groups: 75% were intramuscularly vaccinated with UNISTRAIN® PRRS (attenuated live PRRS vaccine, European genotype; strain VP-046 BIS) and the remaining 25% were administered 2 ml of intramuscular PBS (control group).
Blood samples were collected from the animals to obtain peripheral blood mononuclear cells (PBMCs) on days 0, 7, 14, 28, 42 and 56 post-vaccination. The samples were sent to CReSA (Centre de Recerca en Sanitat Animal) to evaluate cell-mediated immune response by measuring IFN-γ-SC from the PBMCs (ELISPOT assay) (figure 1). Heterologous cell-mediated response was evaluated using five genotype 1 PRRSV strains (table 1) recovered from clinical outbreaks (DIAGNOS, HIPRA), which represent a wide range of strains that were isolated in different European countries in different years. Table 1. Year and country of isolation of five field strains used to evaluate heterologous cell-mediated immune respons.

   
 
RESULTS: 

PRRSV-specific IFN-γ-SC were first detected against all the strains 14 days post-vaccination (figure 2). In the strains isolated in Spain and the United Kingdom, the response peak was found on day 14 post-vaccination; in the Spanish strain, the level found on day 14 was maintained until the end of the study (D56). In the strains isolated in Hungary, the Slovak Republic and Italy, the response peak was found on day 28, after which it declined.

  
In an environment poor in neutralising antibodies, cell-mediated response could be used to evaluate immune response after using a PRRS vaccine and more or less effectively predict protection against the virus.
The objective of the following study was to evaluate the cell-mediated response generated in gilts vaccinated with a PRRRS vaccine (UNISTRAIN® PRRS, HIPRA) against different PRRSV strains isolated from clinical outbreaks in the field.
EXPERIMENTAL DESIGN:

The study was conducted in six-months-old gilts, negative for PRRSV, coming from an historically disease-free farm. The animals were distributed between two groups: 75% were intramuscularly vaccinated with UNISTRAIN® PRRS (attenuated live PRRS vaccine, European genotype; strain VP-046 BIS) and the remaining 25% were administered 2 ml of intramuscular PBS (control group).
Blood samples were collected from the animals to obtain peripheral blood mononuclear cells (PBMCs) on days 0, 7, 14, 28, 42 and 56 post-vaccination. The samples were sent to CReSA (Centre de Recerca en Sanitat Animal) to evaluate cell-mediated immune response by measuring IFN-γ-SC from the PBMCs (ELISPOT assay) (figure 1). Heterologous cell-mediated response was evaluated using five genotype 1 PRRSV strains (table 1) recovered from clinical outbreaks (DIAGNOS, HIPRA), which represent a wide range of strains that were isolated in different European countries in different years. Table 1. Year and country of isolation of five field strains used to evaluate heterologous cell-mediated immune respons.
 

RESULTS: 

PRRSV-specific IFN-γ-SC were first detected against all the strains 14 days post-vaccination (figure 2). In the strains isolated in Spain and the United Kingdom, the response peak was found on day 14 post-vaccination; in the Spanish strain, the level found on day 14 was maintained until the end of the study (D56). In the strains isolated in Hungary, the Slovak Republic and Italy, the response peak was found on day 28, after which it declined.

DISCUSSION AND CONCLUSIONS:

The genetic and antigen variability of PRRSV is considered to be the most important factor in explaining the lack of cross reaction between strains, as heterologous protection is usually inconsistent and incomplete (Lager et al., 1999; Mengeling et al., 1999). On the other hand, the percentage of similarity in the ORF5, or even the complete sequence of the strains, is not a useful parameter for predicting the extent of protection provided by a vaccine against a given strain (Díaz et al., 2006; Prieto et al, 2008).
Although the immunity generated by PRRS vaccine is not fully known, evaluation of neutralising antibodies and cell-mediated response is important and has to be taken into consideration if we want to know how a PRRS vaccine works. The role of cell-mediated immunity for viral elimination or for protecting against a challenge has been discussed and shown in several studies (Díaz et al., 2012; Zuckerman et al., 2007; Lowe et al., 2005; Martelli et al., 2009).
Therefore, in the absence of neutralising antibody production, which is common after the administration of a single dose of any attenuated commercial PRRS vaccine (Díaz et al., 2006; Kim et al., 2008; Zuckerman et al., 2007), the cell-mediated immunity generated by a PRRS vaccine could play an important role in protection against the challenge.
The immunisation of all breeders, and especially gilts, is a key point in the control of PRRS. The main objective in this phase is to obtain good immunisation of gilts, which is why this study was designed using six-month-old gilts.
In this study, despite the wide range of strains used, not only regarding ORF5 variability (88-98% similarity) but also the year of isolation and origin, the results show that vaccination with UNISTRAIN® PRRS induces significant cell-mediated immune response against a wide range of PRRSV strains.
FINAL CONSIDERATIONS 

After more than 25 years confronting PRRS, control of the disease remains a constant challenge for porcine production. The approach to PRRS must be multi-strategic in order to be successful. One of the key aspects of control of this disease is the adaptation programmes for gilts, and their vaccination with UNISTRAIN® PRRS has been shown to be a useful and effective tool.