Segalés: PCV2 and control measures continue to evolve
The development of vaccinations against porcine circovirus 2 (PCV2)-systemic disease (SD) was a huge step in helping producers control one of the most economically important viruses in swine production.
But the virus’s high mutation rates mean surveillance is vital to ensure that vaccination continues to be effective in protecting herds, according to Joaquim Segalés, DVM, PhD, professor in the Department of Animal Health and Anatomy at the Universitat Autònoma de Barcelona and researcher at the Institute of Agrifood Research and Technology (IRTA) – Animal Health Research Center (CReSA), Spain.
“PCV2-SD was a devastating disease before vaccines,” Segalés, an expert in PCV2-SD, told Pig Health Today.
“It wasn’t just mortality — it was the number of runts and pigs with lower weight gain. Vaccination was a huge added value for producers because more animals reached a proper slaughter weight. Even antibiotic expenses diminished significantly because PCV2-SD is an immunosuppressive disease.”
In Segalés’ experience, researchers have been unable to demonstrate real vaccine failure. However, vaccination failure can sometimes be an issue if vaccines aren’t conserved or applied properly, or if the timing of administration isn’t optimized, he said.
A member of the family Circoviridae, PCV2 is considered one of the most economically important viral agents in swine worldwide.1
A single-strand DNA virus, PCV2 has a mutation rate that is relatively high, sometimes comparable to RNA viruses like retroviruses, Segalés said.
It is unique from other porcine circoviruses because both PCV1 and PCV3 have lower mutation rates.2 PCV2 is closely associated with post-weaning multisystemic wasting syndrome,3 which PCV2-SD was initially called.
The most important clinical signs of PCV2 are emaciation and growth retardation; however, respiratory or digestive problems can be present. More importantly, lesions seen through histopathology are of concern, since lymphocyte depletion and granulomatous inflammation of lymphoid tissues are the hallmarks of the disease, Segalés said.
Over time, the virus has changed, largely due to “silent” mutation, meaning the amino acid associated with that particular nucleotide doesn’t change, he added.
Changes in antigenicity are evident when certain monoclonal antibodies are used, but when dealing with a polyclonal response, major differences are not apparent.
Classification modification from a 4- to 8-genotype model
From the beginning, researchers recognized that PCV2 had two, clearly different clusters.4
“Research groups from all over the world started talking about two potential genotypes, but it was confusing because some people used ‘genotype 1,’ ‘genotype 2,’ while others used ‘a’ and ‘b,’” said Segalés, who also served as director of IRTA-CReSA between 2012 and 2017.
In 2008, a European project led by Gordon Allan, PhD, proposed the first genotype definition, in which the existence of two major genotypes, a and b, was proposed to the international community.5
When there was at least a 3.5% difference in the genome, a new genotype could be considered, Segalés said. Over time, the number of sequences grew, and eventually, that separation was not efficient.
PCV2 genotype c was discovered retrospectively in Denmark in the 1980s and has been detected in other countries.6 Then, PCV2d, a mutant form of PCV2b, came along.
“In 2018, Dr. Giovanni Franzo at the University of Padua (Italy) and I developed a better way of distinguishing between genotypes,”7 Segalés said. “We were able to establish eight different genotypes (a, b, c, d, e, f, g and h).”
Some of the genotypes are poorly represented. Most sequences now are from PCV2d, followed by PCV2b and PCV2a, he explained.
Present PCV2 status around the world
PCV2d is the most prevalent circovirus throughout the world, Segalés said. To a high prevalence, it was detected first in China, then in North America and, most recently, Europe.
“Prevalence may reflect the timing in which those sequences were identified, so we have to be careful about the interpretation of adjusting sequences,” he added.
Other genotypes may appear in the future, but as long as they are not mutant escapes from the immunity provided by the vaccine, they are not necessarily relevant for the veterinary community.
“The vaccines really work well,” Segalés said. “But taking into account that this virus changes over time and has a high mutation rate, maintaining a surveillance system is important.”
PCV2 recombination potential
The virus might undergo recombination in a relatively easy manner, Segalés said.
“However, recombination events imply infection of the same cell with two different viruses, and if we’re talking about recombination, we are mostly thinking in terms of different genotypes,” he explained.
“Taking into account the cross-protection between the genotypes, recombination isn’t a major factor to date, since we have only one single protein. In other words, recombination doesn’t seem to affect vaccine efficacy.”
Side-by-side study comparisons have reviewed the efficacy of existing vaccines and their effect on all the genotypes, Segalés said, adding that slight differences are almost impossible to identify.
“The common knowledge is that vaccines are able to control the circulating genotypes,” he said.
Management of PCV2
A small proportion of cases may see overt disease in spite of vaccination, Segalés said, but those cases could have a subpopulation issue.
“The problem is likely not the vaccine but, rather, a change in the epidemiology of the virus,” he said.
“In these cases, we need to get the serology/polymerase chain reaction to identify what’s going on and determine where the infection is taking place. Remember, the end result of systemic disease is multifactorial disease, and there are a number of issues to investigate.”
A proper diagnosis of the condition on the farm is first and foremost, Segalés recommended. Seasonality, facilities, genetics and animal flows should be considered, along with potential infectious agents.
This is key in all cases because even when vaccines are effective, good management is essential in well-run operations.
“We know this virus was already in the pig population in the 1960s, and although we’ve had PCV2 vaccines for slightly more than a decade, we are still happy with the protection offered,” Segalés said.
“There’s a typical saying we use here in Spain,” he added. “If something works, don’t touch it. In other words, there is no need to change anything regarding vaccination against PCV2 if there is no evidence for it.”
1 Saporiti V, Huerta E, Correa-Fiz F, Grosse Liesner B, Duran O, Segalés J, Sibila M. Detection and genotyping of Porcine circovirus 2 (PCV-2) and detection of Porcine circovirus 3 (PCV-3) in sera from fattening pigs of different European countries. https://pubmed.ncbi.nlm.nih.gov/32356364/ Accessed Nov. 6, 2020.
2 Yee Tan C, Opaskornkul K, Thanawongnuwech R, Hassan L, Toung Ooi P. First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia. 2020 July 24. https://doi.org/10.1371/journal.pone.0235832
3 Khaiseb S, Sydler T, Zimmermann D, Pospischil A, Sidler X, Brugnera E. Coreplication of the Major Genotype Group Members of Porcine Circovirus Type 2 as a Prerequisite to Coevolution May Explain the Variable Disease Manifestations. J Virol. 2011 Nov;85(21):11111-11120 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194933/ Accessed Nov. 6, 2020.
4 Olvera A, Cortey M, Segales J. Molecular evolution of porcine circovirus type 2 genomes: Phylogeny and clonality. https://doi.org/10.1016/j.virol.2006.07.047 Accessed Nov. 6, 2020.
5 Timmusk S, Wallgren P, Brunborg I, Wikstrom F, Allen G, Meehan B, McMenamy M, McNeilly F, Fuxler L, Belak K, Podersoo D, Saar T, Berg M, Fossum C. Phylogenetic analysis of porcine circovirus type 2 (PCV2) pre- and post-epizootic postweaning multisystemic wasting syndrome (PMWS). Vet Microbiol. 2008 June 1. https://www.sciencedirect.com/science/article/pii/S0378113507004749 Accessed Nov. 6, 2020.
6 Dupont K, Nielsen EO, Bækbo P, Larsen LE. Genomic analysis of PCV2 isolates from Danish archives and a current PMWS case-control study supports a shift in genotypes with time. Vet Microbiol. 2008;128:56-64. 10.1016/j.vetmic.2007.09.016
7 Franzo G, Segales, J. Porcine circovirus 2 (PCV-2) genotype update and proposal of a new genotyping methodology. 2018 Dec. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208585 Accessed Nov. 6, 2020.
Posted on February 1, 2021