PRRS Swine virus is known for its capacity to mutate. Worldwide, two major genotypes are known and so are many strains – with many different levels of pathogenicity. This type of threat needs a cure which is as versatile as its enemy, as was shown at various congresses around the globe.
The Porcine Reproductive and Respiratory Syndrome virus (PRRSv) is a moving target. It possesses the distinctive feature of being able to emerge in altered forms virtually by default, each time it replicates. So rapidly does it change in this way that it is now considered to have the highest rate of evolution of any member of the group classed as RNA viruses.
When PRRSv mutates, most of the mutations are non-viable and therefore disappear as soon as they occur. But a few of them manage to survive and add to the agents encountered on farms. In addition, if two different viruses infect the same cell, they can exchange genetic material (recombinations).
The overall result of this constant process of change is a genetic diversity for PRRSv that is already wide and is still growing. This creates a greater need for PRRS vaccines to be able to deal with a heterologous challenge, involving multiple forms of the virus that differ in their genetics from the vaccine’s source agent and are only partially related to each other genetically.
Challenges with virulent isolates
That was the background of a study described to the 2013 Leman conference, in which pigs vaccinated using Ingelvac PRRS MLV (Boehringer Ingelheim) were challenged afterwards with eight genetically different PRRSv isolates. Consistently and significantly, the vaccination reduced the percentage of lung lesions found in the challenged animals during their growing period compared to their non-vaccinated/challenged counterparts.
Even with the range of isolates in this case, however, the question remained whether the modified-live vaccine offered cross-protection against the PRRSv strains considered to be the most relevant current threat.
Examples of newly emerging strains affecting American farms have since been tried in follow-up challenge studies. One of these took a highly virulent PRRSv variant which, in the US classification system, was labelled as RFLP 1-7-4. In results presented to the 2016 IPVS Congress and also to the AASV meeting in that year by Boehringer Ingelheim’s Greg Haiwick and others, vaccination of growing pigs before they were challenged with this ‘174’ isolate successfully limited PRRS-induced lung lesion development while significantly improving daily growth rate, also see Figures 1and 2. An update in 2018 at the 25th IPVS Congress in Chongqing, China, observed that the vaccinated group in the study had a 61% higher average daily growth rate when compared to challenge control animals.
Figure 1 – Percentage of viraemic pigs per treatment group challenged with 4 logs of PRRSv SDSU-73.
The vaccine had been administered to 159 PRRSv-free pigs at 3 to 4 weeks old (day 0 of study) and 28 days prior to the virulent PRRSv ‘174’ challenge (day 28 of study). Both vaccinated and non-vaccinated groups of challenged pigs were evaluated during a 14-day post-challenge period, after which they were necropsied and the lungs assessed for lesions (day 42 of study). Over this study period a significant reduction was also measured for post-challenge viraemia, comparing the vaccinated pigs to the non-vaccinates.
The 2017 Leman conference, held in St Paul, MN, USA, added another chapter to the story when the same investigators reported a challenge study involving a separate isolate tagged as RFLP 1-3-4, by now newly emerging on pig farms in the USA with field reports describing severe clinical consequences. Compared to pigs given a non-vaccine placebo, the vaccinated group was significantly better for absence of lung lesions, rate of weight gain per day and percentage mortality up to the end of the study.
Figure 2 – Percentage of viraemic pigs per treatment group challenged with 2 logs of PRRSv SDSU-73.
Influence of dose size
The new information from this series of studies is demonstrating that the efficacy of the vaccine should be measured not only by the identity of the viral strains, but also by the level or quantity of challenge virus in the challenge dose. A comprehensive evaluation of challenge doses in relation to the aforementioned vaccine usage was summarised at IPVS 2016 by Haiwick and others. It employed a logarithmic scale to express the large numbers of viruses per dose, from a starting point of log 1 to logs 2, 3 and 4.
The study design began by vaccinating 90 PRRSv-free pigs at 21 days of age. Then at 28 days old they were challenged using the different dose levels, followed by monitoring of biological effects up to an age of about 90 days.
The research team wanted to find what challenge dose of virulent PRRSv was required to cause infection in a vaccinated animal and the outcomes of infection that arose. A dose-dependent response was soon apparent. At all four dose sizes, the use of the PRRS vaccine mitigated the consequences of infection as compared to challenged controls. But at a challenge of log 2 or less, the health and performance measured for the vaccinated pigs were as good as those of the non-challenged animals.
Measuring viraemia, temperature and ADG
This dose-related effect was seen when measuring viraemia, body temperature and average daily weight gain. At every level of challenge there had been a clearly negative impact on the non-vaccinated controls. Yet when challenge doses of virus dropped to log 2 or below, vaccination either prevented the consequences of infection or stopped it from damaging growth performance.
The finding has practical implications. A low dose exposure of virus can certainly happen in the field. Under those circumstances vaccinating evidently offers the chance to prevent any ill-effects on the pigs. Moreover, the studies showed the added benefit of less shedding of virus in vaccinated pigs . A large-scale PRRS control project in the USA found vaccination was associated with a 50% reduction in the number of wild-type PRRSv strains detected in the production system. Other observations made in the field have described substantial reductions in the frequency and duration of detection of PRRSv in the air, where pigs were vaccinated before challenge.
|PRRS and genetics
One key question in the immunology of PRRS has been whether the protection afforded by a vaccine depends on matching genetics. Answers to these types of questions can be found in a modern science known as phylogenetics.
Early indications from whole-genome sequencing have already shown that PRRSv forms are even more variable than previously thought. Where once it was common to talk of a European-type PRRS and a North American type, their modern names are PRRSv-1 and PRRSv-2 and they are now considered as two distinct species – both of which occur globally.
Within each one are huge genetic differences between the viral forms belonging to the species. The diversity seems to be even greater within PRRSv-1 than in PRRSv-2. Normally the level of heterology (difference between strains) is given as a percentage, such as when saying a wild-type isolate is 10% different to a particular vaccine virus. On this basis the diversity of genetics among PRRSv-1 is reckoned at up to 30%, compared with 20% in PRRSv-2. Detailed research has also established that there are no genetic markers in the PRRS virus that can give any hint of virulence for an isolate or how it will behave clinically.
So to come back to the question asked in the first sentence: There is no genetic information that can tell how well a given PRRS vaccine will protect. Some vaccines are simply better than others at providing cross-protection where multiple PRRSv variants are involved.
Source: Pig Progress
Cladan Nutricion y Salud Animal
US researchers have produced a litter of pigs of which they claim they are genetically resistant to Transmissible Gastroenteritis virus (TGEv), causing gut disease with almost 100% mortality in piglets.
The team, consisting of researchers from the University of Missouri (MU), Kansas State University and breeding company Genus, has succeeded in breeding pigs that are resistant to the virus by means of gene editing. They shared their findings in a recent publication in the peer-reviewed publication Transgenic Research.
Enzyme as receptor for TGE virus
In a news article shared by the University of Missouri, Randall Prather, professor of animal sciences, said, “Previous research had identified an enzyme called ANPEP as a potential receptor for the virus, meaning it could be an important factor in allowing the virus to take hold in pigs.
“We were able to breed a litter of pigs that did not produce this enzyme, and as a result, they did not get sick when we exposed them to the virus.”
The news article explained how Prof Prather and his colleagues edited the gene responsible for making the ANPEP enzyme, resulting in a litter of 7 pigs with a ‘null’ gene that did not produce the enzyme. When exposed to the TGEv virus, these pigs did not become infected, showing that the presence of the ANPEP enzyme is necessary for an infection and gene editing can create pigs that are resistant.
Genetic resistance will help to ease the burden
Kristin Whitworth, co-author on the study and an MU research scientist, added, “It’s a tremendous financial burden for farmers to put time, money and labour into animals that will get sick. Breeding pigs with genetic resistance will help to ease that burden. In terms of animal welfare, if we can prevent these pigs from getting sick, we have a responsibility to do so.”
In comparison to the scores of gene mutations that occur naturally during the reproductive process, researchers only altered the expression of a single gene. Those pigs lacking the enzyme were healthy and experienced no changes in development.
Porcine coronaviruses are a global threat
Raymond ‘Bob’ Rowland, professor of diagnostic medicine and pathobiology at Kansas State University, was also one of the co-authors of the study. In the news article, he commented: “The collaboration with Randy and his team has established some of the most rewarding milestones of my career. Porcine coronaviruses are a global threat to the pig industry. One of the greatest concerns for US producers are outbreaks of new coronaviral diseases.
“Once again, this work demonstrates the importance of this technology in solving complex disease problems. Genetic modification to protect pigs from endemic and emerging diseases is the future of the pork industry.”
Similar approach to PRRS virus
The study follows a similar development achieved in 2015, when MU’s genetic engineering team made pigs resistant to Porcine Reproductive and Respiratory Syndrome (PRRS) virus by using gene editing.
The University of Missouri partnered with Genus to commercialise that method of producing virus-resistant pigs. Genus is currently seeking FDA approval for the use of gene editing technology for use in eradicating the PRRS virus.
The study also sought to determine whether editing out ANPEP would produce resistance to Porcine Epidemic Diarrhoea virus (PEDv), which killed nearly 7 million pigs in a 2013 outbreak. While pigs lacking the enzyme still contracted the virus, researchers are optimistic that the study bodes well for future research.
The study was published in Transgenic Research. Researchers involved in the study were Randall Prather, Kristin Whitworth, Melissa Samuel and Kevin Wells, University of Missouri, Columbia, MO, United States; Raymond Rowland, Vlad Petrovan, Maureen Sheahan, Ana Cino-Ozuna, Ying Fang and Richard Hesse, Kansas State University, Manhattan, KS, USA; and Alan Mileham of Genus.
What do cartoon vehicles and pig production have in common? More than you would think. Nutrition technology expert Dr Casey Bradley got inspired by the problem-solving scenarios on television and shares some new insights.
New in my life again are cartoons and my son Arthur’s favourite cartoon today is, ’Stinky and Dirty’, which is based around problem-solving scenarios. Some of the most memorable lines are: ”What if…?”; ”I know what you are doing… you’re thinking”; ”Let me help! Let me help!”
But back to the realm of nutrition, I am now going on my 8th year in the feed industry and not going to tell you how many years in the swine industry… as you know I was born into the profession. These years do not include the 8 years managing swine research for the University of Arkansas.
But with both jobs I have been involved with a large amount of research trials. My biggest frustration of research is that pigs do not always read the protocol or that what we hypothesise is not always true or proven. Along the way investment of time and money appears lost, but new questions are developed and forward progress moved with smaller strides.
“Every trial leads to more questions than answers!”
Technology has also exploded over my career and has brought many opportunities for mankind and pigs alike. This has allowed USA swine producers the opportunity to invest in their own large-scale research facilities with the help of automated feeding systems, scale improvements, RFIDs, etc.
But limitations with number of treatments and number of trials exist within these facilities too. Also, individual producers must conduct their own internal trials before implementing any nutritional changes, resulting in repetitious research with limited sharing of the results throughout the industry. Thus, creating a bottle neck for forward progress through nutrition… And a lack of resources for much needed research in the swine industry.
‘Stinky & dirty’ vs ‘pristine & clean’
This to me relates to ’in vivo’ vs ’in vitro’ opportunities. Many of my colleagues know that I am a ‘boots on the ground’ kind of person. I must see it to believe it and I am at my best in a hog barn.
But entering the realm of feed additives, my view point of the industry has changed dramatically over the last 5 years. I have spent countless hours in a laboratory during my graduate student days and have a great appreciation for scientists who are at their best in the laboratory versus the hog barn alike.
What if we create an ‘artificial pig’ model? This is what is keeping me awake at night lately. Currently today we have 2 unique directions into this area: digestibility and fermentation models and then an innate immune model utilising IPEC-J2 cell line (intestinal porcine epithelial cells) and now possibly swine enteroids, which are essentially tiny guts that can be grown in petri dishes, as a team around Trudeau showed in 2017.
Both areas provided better opportunities for not only researchers, but producers alike to better understand feed additives before they are fed to pigs, with limited cost and quicker turn-around times.
If we better understand the mode of actions of feed additives, then we will be able to widen the bottle-neck for forward progress in nutrition. With the right minds coming together my dreams of an ‘artificial pig’ will be possible. But in the meantime, I encourage field nutritionists to read up on these different in vitro assays and models, and maybe find a novel opportunity to improve pig performance in your systems.