What has changed about porcine circovirus epidemiology?

Interview with Oliver Duran, Leader of the Global Swine Technical team at Boehringer Ingelheim Animal Health.

Have there been any changes to the PCV2 vaccination protocols for replacement and breeding animals?

Today vaccinating replacement animals is an established practice, but routine vaccination of sows is much less common. As this disease has an epidemiology with many factors involved, there are different hypothesis: some theories say that vaccination and a subsequent infection of the virus present in the environment would be enough to generate a solid immunity and not see instability on the farm.

On the other hand, batches of seronegative gilts have been documented. These gilts, arriving seronegative at the sow farm, and therefore fully susceptible, are a risk. When the replacement females are not vaccinated and there is no field infection due to the last 15 years of constant vaccination pressure, a situation can occur where we have a sow farm that is very susceptible to PCV2. This can generate two problems: in the growing animals produced by these females and in the females themselves, causing reproductive problems. These two problems do not have to happen together nor do all farms present reproductive problems.

This makes us realize the importance of having a good continuous monitoring plan, to assess whether the epidemiological situation is changing, and to manage risk analysis. Implementing routine vaccination of sows gives you an extra level of security and is usually implemented on farms that have had reproductive problems due to PCV2. Each circumstance must be analyzed individually.

There is debate about how mass vaccination on farms and vaccination of breeding stock has affected the epidemiology of the infection. What do you think about this?

This issue is controversial. There are cases where the virus is reported to be present in the piglet at farrowing, indicating a high transmission of PCV2 from the sow to the piglet. And in those cases, mass vaccination of the sows has been shown to change the dynamics and reduce early infection in the piglet. Cases have been seen in the USA and in Spain, but this is not a global observation.

How these piglets, which are born infected with PCV2 and are protected with maternal antibodies, respond to vaccination is somewhat difficult to replicate in the laboratory. Typically the epidemiology shows early clinical cases (2-3 weeks post weaning). When farms that routinely vaccinate observe clinical problems with PMWS, the first thing to do is to find out if the vaccination guidelines were carried out correctly or if the problem really arises from the fact that the animals were already infected at the time of vaccination. The latter situation has been seen in sporadic cases, but does not correspond to the majority of cases observed. My colleagues and I see, on occasion, cases where vaccination is not being carried out correctly; either due to human error (vaccination with inadequate dose, incomplete vaccination of a batch or group, poor vaccination technique), or due to poor handling of the product, or failing to carry out the vaccination at all.

It is important to emphasize that in the recommended vaccination program with Ingelvac CircoFLEX^®, vaccinating the sows is never a substitute for vaccinating piglets.

When should a farm consider that it may have a reproductive problem related to PCV2?

The typical cases most commonly seen are new farms with a population made entirely of gilts, and it is noted that the farm is not getting the reproductive results that would be expected considering the genetics it is working with. We should not expect large numbers of abortions, stillbirth, etc. It more so has to do with a loss of reproductive efficiency that is sometimes difficult to diagnose. In some cases it can resemble parvovirosis, with an increase in the number of mummies, which even if not dramatic can be detected if there is a good data collection system in place (Photo 1).

A good sample of stillborns and mummies is required for a correct diagnosis. The detection of histological lesions in organs, in combination with antigen detection, either by PCR or by immunohistochemistry, allows confirmation of PCV2 infection.

And how does the presence of maternal antibodies affect the efficacy of piglet vaccination?

Each vaccine is different in its composition, adjuvant, and in the way it generates immunity, all of which affect how it works in the field. The question of how the vaccine works in the presence of maternal antibodies is not new and we have recently published new data (link to paper) evaluating the individual behaviour of piglets in the presence of different levels of maternal antibodies at the time of vaccination (Low-High-Very High). In all cases, vaccinated animals had better growth performance compared to unvaccinated animals, regardless of the level of antibodies present at the time of vaccination. Piglet vaccination in that study (Ingelvac CircoFLEX^® ) improved average daily gain (ADG), reduced mortality, and reduced PCV2 viraemia regardless of the level of maternal antibodies at the time of vaccination.

These good results from vaccination in the presence of high maternal antibody levels probably are due to the fact that the aim of Ingelvac CircoFLEX^® is to generate an immune response directed at cellular immunity, which appears to be not as susceptible as a response that would require more antibody involvement. Studies at the University of Vienna showed protection was due to the generation of high levels of CD4⁺ T cells that induce the production of cytokines effective against PCV2 (Koenig et al 2015). Conversely, it has been shown that high titres of non-neutralizing antibodies do not correlate with protection (Tribble et al 2012). This type of response is given by the design of Ingelvac CircoFLEX^® in relation to the antigen and especially to the adjuvant, ImpranFLEX^®, is very much directed at cell-mediated immunity and not so much at antibodies.

Knowledge of the basic characteristics of the vaccine that we use on the farm is important in order to be able to assess other elements. For example, this increased focus on stimulating cell-mediated immunity means that not all animals who haven't been exposed to the field virus and were vaccinated with Ingelvac CircoFLEX^® will demonstrate seroconversion on commercial ELISA tests, but are nevertheless protected against PCV2.

Are we controlling subclinical PCV2 infection?

The impact of subclinical disease is difficult to measure as it depends on a multitude of farm-specific factors which are difficult to replicate in the lab. We have seen situations where, in the context of very low prices, farms cut back on the use of vaccine (for example, by administering half doses). Then, perhaps without resulting in mortality, as in typical PMWS cases, these farms observed situations where a significant negative effect on growth happened (Photo 2). Veterinarians who fought PMWS before the advent of the first PCV2 vaccines are fully aware of the impact that subclinical PCV2 infection has. For younger veterinarians who did not experience the impact of the disease, it has basically become a routine vaccine, making it more difficult for them to gauge the value.

Do veterinarians have good diagnostic techniques available?

The techniques exist, but it is important to use and interpret them correctly in order to draw valid conclusions that will help us find a solution.

It is always essential to start from a good diagnosis, which is increasingly more difficult in some systems with a growing number of animals to be monitored per veterinarian. We often see a lack of an in-depth diagnosis, either directly by lack of diagnostic confirmation, or because there really are mixed infections caused by several pathogens. When we see an animal that loses weight in the post weaning period, many times it is thought to be related to PCV2 and wasting disease, when really we must remember that there are many management, nutritional, or environmental factors, or other pathologies that could be causing clinical signs relatively similar to PMWS (Picture 3).

It is important to combine more than one diagnostic technique: PCR with histology, PCR together with a good clinical evaluation or correctly executed necropsies. Drawing conclusions based solely on PCR results does not provide enough information to be able to offer suitable solutions. PCR can detect virus in extremely low amounts, but what does a PCV2-positive PCR result mean when we know that vaccination does not completely eliminate virus presence? More powerful diagnostic techniques require a greater need for correct interpretation so as not to fall into erroneous conclusions that put us further from a solution.

PCV-2 strains vary over time. How does this affect the protection we can expect from vaccines?

We must always be on the lookout for new strains and new serotypes. Boehringer Ingelheim has a monitoring program for new strains and viruses. The aim of this program is to check, when a new strain emerges, that the vaccines we currently have on the market provide adequate protection against them or, if necessary, to take measures for future developments. So far, through experimental infections with the new PCV2 strains that have appeared, we have been able to demonstrate that Ingelvac CircoFLEX^® also provides coverage for the new strains. We also gain a lot of valuable information from the experiences of our customers. We have conducted studies on farms where vaccination can be considered very successful, with no clinical cases, but where circovirus can be detected. Here we see that the genetic profile of PCV2 strains is varied and yet the vaccine works.

But the world of viruses is a dynamic one and this ongoing program of monitoring, whether through communication with our customers or collaboration with research groups, is key to staying informed of what is happening at the farm and being prepared if changes occur.

PCV3 and recently PCV4 viruses have also been discovered. Do we know what the implications of these viruses are?

PCV3 and PCV4 are very different viruses, with little genetic similarity to PCV2 and so there is no expectation that PCV2 vaccines will be effective against these other viruses.

To date, very sporadic cases of problems associated with PCV3 have been reported, where the virus had a slight effect on reproductive parameters, which was not easy to detect. It is also true that PCV3 has been isolated from healthy animals and from farms without any problems. But many things can change: the susceptibility of the pigs, the virus itself, or other elements. For example, PCV2 was present in the population 20 years before the serious clinical problems we did experience arose. We therefore believe that it is important to maintain this active surveillance to be as well prepared as possible in the event of any change.

Regarding PCV4, this virus has been recently discovered in China where it was detected in some clinical cases where other infections were present. It is too early to know if it will have any clinical relevance.

What challenges does porcine circovirus pose for the future?

We must not forget the impact that PMWS had on the pig industry so that we remember the need to continue implementing PCV2 vaccination correctly. We know that the problems would return the moment vaccination were to stop. We continue working to define the ideal control program where we can get the maximum benefit from the investment in the vaccine and avoid situations where the cost of the vaccine is wasted, either due to errors in administrating the vaccine, the vaccination schedule, or failure to cover the different areas of the farm: sows, fattening and replacement.

To continue providing value to the client, the communication established with the field veterinarians is essential, as well as the direct work our colleagues do with the clients.

Another challenge on the forefront is approaching the farm's health as a whole and not so much by assessing viruses or products in an isolated fashion. Look for strategies to maximize productivity, considering all the challenges as a whole instead of assessing a specific virus without considering the overall situation. Such comprehensive approaches must address all relevant elements ranging from biosecurity, correct All In/All Out flow, to attention to detail, all of which are important along with the correct choice and application of the vaccine.