Deletion of a decoy epitope in porcine circovirus 2 (PCV2) capsid protein affects the protective immune response in mice.

The swine pathogen porcine circovirus type 2 (PCV2) causes significant economic damage worldwide. The PCV2 capsid (CP) residues 169-STIDYFQPNNKR-180 have been identified as a decoy epitope that diverts the host immune response away from protective epitopes. However, the decoy epitope may include important linear or conformational protective epitopes against PCV2. In this study, we used the baculovirus system to express recombinant complete CP (1-233) and mutant CP (Δ169-180), in which the decoy epitope was deleted, and evaluated the immune response to these in mice. Immunization with mutant CP (Δ169-180) protein, which formed very low level of virus-like particles (VLPs), elicited significantly lower levels of PCV2 CP-specific IgG antibodies and a slightly lower neutralizing activity than immunization with the complete CP (1-233) protein. This finding suggests that the complete CP is important for efficient VLP assembly and induction of PCV2-specific IgG antibodies and neutralizing antibodies in mice. This study may provide useful information for next-generation vaccine design for PCV2 control.

A Heterologous Viral Protein Scaffold for Chimeric Antigen Design: An Example PCV2 Virus Vaccine Candidate.

Recombinant vaccines have low-cost manufacturing, regulatory requirements, and reduced side effects compared to attenuated or inactivated vaccines. In the porcine industry, post-weaning multisystemic disease syndrome generates economic losses, characterized by progressive weight loss and weakness in piglets, and it is caused by porcine circovirus type 2 (PCV2). We designed a chimeric antigen (Qm1) to assemble the main exposed epitopes of the Cap-PCV2 protein on the capsid protein of the tobacco necrosis virus (TNV). This design was based on the Cap-N-terminal of an isolated PCV2 virus obtained in Chile. The virus was characterized, and the sequence was clustered within the PCV2 genotype b clade. This chimeric protein was expressed as inclusion bodies in both monomeric and multimeric forms, suggesting a high-molecular-weight aggregate formation. Pigs immunized with Qm1 elicited a strong and specific antibody response, which reduced the viral loads after the PCV2 challenge. In conclusion, the implemented design allowed for the generation of an effective vaccine candidate. Our proposal could be used to express the domains or fragments of antigenic proteins, whose structural complexity does not allow for low-cost production in Escherichia coli. Hence, other antigen domains could be integrated into the TNV backbone for suitable antigenicity and immunogenicity. This work represents new biotechnological strategies, with a reduction in the costs associated with vaccine development.

Reduction of Postweaning Multisystemic Wasting Syndrome-Associated Clinical Symptoms by Virus-Like Particle Vaccine Against Porcine Parvovirus and Porcine Circovirus Type 2.

The porcine circovirus type 2 (PCV2) capsid (Cap) protein and porcine parvovirus (PPV) VP2 protein have been studied in vaccines to control postweaning multisystemic wasting syndrome (PMWS). Virus-like particle (VLP) vaccines are nonreplicative vectors that deliver epitopes and induce immune responses. However, most VLP vaccines are recombinant proteins expressed in eukaryotic systems and are expensive and complex. In this study, the full-length PCV2-Cap and PPV-VP2 proteins were expressed in Escherichia coli, which self-assembled into VLPs. The highly soluble proteins were purified using Ni-chelating affinity chromatography. The proteins self-assembled into VLPs of ∼20 nm (Cap VLP) and 25 nm (VP2 VLP) in diameter. The immunogenicities of Cap VLP and VP2 VLP were determined in piglets coinfected with PPV and PCV2 postimmunization. The results suggested that Cap VLP and VP2 VLP did not antagonize each other. The combined vaccine induced stronger humoral and cellular immune responses and provided the best protection against PPV and PCV2 coinfection. On a farm containing PMWS-infected pigs, the combined Cap VLP and VP2 VLP vaccine significantly improved piglet growth indices; the average daily weight gains were significantly higher than those of the Cap VLP vaccine and nonimmunized groups. Thus, Cap and VP2 protein expression in E. coli is feasible for large-scale VLP vaccine production. The combined vaccine may be a promising candidate vaccine for better preventing PMWS-associated diseases coinfected with PCV2 and PPV.

Incorporation of ORF2 from Porcine Circovirus Type 2(PCV2) into genetically encoded nanoparticles as a novel vaccine using a self-aggregating peptide.

Porcine Circovirus Type 2 (PCV2) is one of the most important pathogens in pigs around the world. PCV2 is a non-enveloped virus and its capsid is formed by a single protein known as open reading frame 2 (ORF2). The aim of this study was to evaluate the antigenicity and immunogenicity of genetically-encoded protein nanoparticles (NPs) containing ORF2 from PCV2 fused to the first 110 amino acids of the N-terminus of polyhedrin from the insect virus Autographa californica nucleopolyhedrovirus (PH(1 -1 1 0)). Our group has previously described that some polyhedrin fragments self-aggregate forming polyhedra-like particles. We identified a self-aggregating signal within the first 110 amino acids from polyhedrin (PH(1 -1 1 0)). Fusing the ORF2 from PCV2 to the carboxyl terminus from PH(1 -1 1 0) results in the formation of NPs which incorporate the antigen of interest. Using this system we synthesized NPs containing PH(1 -1 1 0) fused to ORF2 (PH(1 -1 1 0)PCV2) and purify them to immunize pigs and evaluate the humoral immune response generated by these NPs comparing them to a commercially available vaccine. Pigs immunized with PH(1 -1 1 0)PCV2 NPs produced antibodies against ORF2 from PCV2 as indicated by western blot and ELISA analysis. Antibodies obtained with PH(1 -1 1 0)PCV2 NPs were comparable to those obtained using a commercial PCV2 vaccine. These antibodies neutralized the infection of a recombinant PCV2 expressing the green fluorescent protein (GFP). These results together suggest that the self-aggregating peptide PH(1 -1 1 0) can be used for the synthesis of subunit vaccines against PCV2.

Purification and characterization of immunogenic recombinant virus-like particles of porcine circovirus type 2 expressed in silkworm pupae.

Porcine circovirus type 2 (PCV2) is a primary causative agent of postweaningmultisystemic wasting syndrome (PMWS), which has a significant economic impact on the swine industry. The capsid protein (Cap) encoded by ORF2 of the viral genome has been used effectively as a vaccine against PCV2 infection. The Cap protein can spontaneously assemble into virus-like particles (VLPs) that are safe and highly immunogenic for vaccine applications. Several expression systems, including bacteria, yeast and insect cells, have been utilized to produce PCV2 VLPs. However, in some cases, the recombinant Cap (rCap) proteins produced in bacteria and yeast do not assemble spontaneously. In this study, we expressed rCap protein using a silkworm-baculovirus expression vector system (silkworm-BEVS) for mass production of PCV2 VLPs and established a simple three-step protocol for its purification from pupae: extraction by detergent, ammonium sulfate precipitation and anion exchange column chromatography. Size-exclusion chromatography (SEC) analysis and transmission electron microscope (TEM) observation showed that purified rCap proteins formed VLPs with a similar morphology to that of the original virus. Furthermore, the VLPs produced in silkworms were capable of inducing neutralizing antibodies against PCV2 in mice. Our results demonstrated that the silkworm system is a powerful tool for the production of PCV2 VLPs and will be useful for the development of a reliable and cost-effective PCV2 vaccine.

Enhancement of immune response of piglets to PCV-2 vaccine by porcine IL-2 and fusion IL-4/6 gene entrapped in chitosan nanoparticles.

In order to develop a novel effective immunomodulator to enhance pig resistance against post-weaning multi systemic wasting syndrome (PMWS), a recombinant plasmid co-expressing pig interleukin-2 (IL-2) and fusion interleukin-4/6 (IL-4/6) genes, designated VRIL4/6-2, was constructed and encapsulated in chitosan (CS) nanoparticles prepared by the ionotropic gelation method. Then 21-day old piglets were divided into two groups and intramuscularly injected respectively with VPIL4/6-2-CS and saline along with the porcine circovirus-2 (PCV-2) vaccine. The blood was collected from each piglet on days 0, 7, 14, 28, 56 and 84 after vaccination to assay the immunological changes. Content of IgG2a, CD4+, CD8+ T cells increased significantly in the sera or blood of piglets treated with VPIL4/6-2-CS (P<0.05). Furthermore, the expression level of IL-2, IL-4, IL-6, IL-15, TLR-2, TLR-7, Bcl-2, TNF-α, CD45 and STATs (STAT1, STAT2, STAT3, STAT4) genes were significantly elevated in the treated piglets respectively in different days after inoculation (P<0.05). The growth weight gain of the treated piglets was markedly improved in comparison with the controls (P<0.05). These indicate that VPIL-4/6-2 entrapped with chitosan nanoparticles is a safe and promising effective adjuvant to promote the immune response of pig to PCV-2 vaccination.

Porcine circovirus type 2 protective epitope densely carried by chimeric papaya ringspot virus-like particles expressed in Escherichia coli as a cost-effective vaccine manufacture alternative.

Porcine circovirus type 2 (PCV2) still represents a major problem to the swine industry worldwide, causing high mortality rates in infected animals. Virus-like particles (VLPs) have gained attention for vaccine development, serving both as scaffolds for epitope expression and immune response enhancers. The commercial subunit vaccines against PCV2 consist of VLPs formed by the self-assembly of PCV2 capsid protein (CP) expressed in the baculovirus vector system. In this work, a PCV2 protective epitope was inserted into three different regions of papaya ringspot virus (PRSV) CP, namely, the N- and C-termini and a predicted antigenic region located near the N-terminus. Wild-type and chimeric CPs were modeled in silico, expressed in Escherichia coli, purified, and visualized by transmission electron microscopy. This is the first report that shows the formation of chimeric VLPs using PRSV as epitope-presentation scaffold. Moreover, it was found that PCV2 epitope localization strongly influences VLP length. Also, the estimated yields of the chimeric VLPs at a small-scale level ranged between 65 and 80 mg/L of culture medium. Finally, the three chimeric VLPs induced high levels of immunoglobulin G against the PCV2 epitope in immunized BALB/c mice, suggesting that these chimeric VLPs can be used for swine immunoprophylaxis against PCV2.

Assessing PCV2 antibodies in field pigs vaccinated with different porcine circovirus 2 vaccines using two commercial ELISA systems.

Porcine circovirus type 2 (PCV2) is the primary causative agent for post-weaning, multisystemic, wasting syndrome. Consequently, serologic detection of and vaccination against PCV2 are important for the swine industry. Among several serological tests, the enzyme-linked immunosorbent assay (ELISA) is commonly used to measure anti-PCV2 antibody levels. In the present study, we used two commercial ELISA systems to comparatively evaluate anti-PCV2 antibodies in field pigs treated with three different PCV2 vaccines. Among a total of 517 serum samples, the results of the two ELISAs were fully concordant for 365 positive and 42 negative samples, indicating 78.7% agreement. In addition, the Pearson coefficient (0.636) indicated a moderate correlation between data from the two ELISAs. Results from the farms with pigs vaccinated with the three different PCV2 vaccines demonstrated that most of the vaccinated animals underwent seroconversion. However, the increase and duration of antibody titers varied depending on the vaccine, the presence of maternal antibodies, and the vaccination program. PCV2 serologic status and anti-PCV2 antibody levels of herds from this study could be utilized to determine the best timing for vaccination and assessing vaccination compliance.

Best practice and future challenges for vaccination against porcine circovirus type 2.

Porcine circovirus type 2 (PCV2)-systemic disease (SD) (initially named as postweaning multisystemic wasting syndrome) was discovered as an occasional disease affecting postweaning pigs in North-America by mid-1990s. Soon afterward, it was noticed as a devastating disease worldwide. Such scenario prompted to develop vaccine prototypes that worked fairly well under experimental conditions. In spite of the multifactorial nature of the PCV2-SD, the first commercialized vaccines containing inactivated or chimeric PCV2 viruses or PCV2 Cap protein represented by far the best system to control the disease under farm conditions. Moreover, vaccination of non-clinically affected pigs demonstrated a significant improvement of average daily weight gain and, in consequence, the economic importance of the PCV2-subclinical infection. In the present review, a comprehensive overview on PCV2 vaccines and best practices on PCV2 vaccination strategies are presented and discussed.

The presence of six potentially pathogenic viruses in pigs suffering from post-weaning multisystemic wasting syndrome.

BACKGROUND: Porcine circovirus type 2 (PCV2) is an etiological agent of porcine circovirus diseases (PCVDs). Post-weaning multisystemic wasting syndrome (PMWS) as the most important PCVD is considered a multifactorial disease. It was demonstrated that not only PCV2 but several viruses are associated with PMWS. Studies of viral co-infections in PMWS pigs led often to controversial results. The aim of this work was to determine the presence of emerging (PRRSV), re-emerging (PTV) and newly-emerging (TTSuV1, TTSuV2, PBoV1) viruses in samples of dead pigs suffering from PMWS. The impact of vaccination against PCV2 and the influence of age on the occurrence of single and multiple viral infections in pigs were also investigated. RESULTS: Viruses were detected by PCR, RT-PCR and real-time PCR in the pooled tissue samples (lymph nodes, liver and spleen) of pigs with PMWS (n = 56) which were divided into three groups: suckling piglets, post-weaning pigs and fattening pigs. In addition, lymph node samples were collected from apparently healthy fattening pigs (n = 59). The effect of vaccination against PCV2 with Ingelvac CircoFlex vaccine was also investigated. Between non-vaccinated pigs, the highest prevalence of individual viruses and multiple viral infections were found in diseased post-weaning and fattening animals with PMWS. Severe clinical disease was observed in swine co-infected with PCV2 and PRRSV. The prevalence of TTSuV1 and TTSuV2 was high in all groups of pigs and did not appear to have a significant effect on the syndrome. Simultaneous infection with TTSuV1 and PBoV1 was frequently confirmed in pigs with PMWS. No healthy pig was found to be infected with PRRSV, PTV or PBoV1. Vaccination against PCV2 did not influence the prevalence of TTSuVs, but significantly protected pigs against multiple viral infections. CONCLUSIONS: Post-weaning PMWS pigs were more often co-infected with viral pathogens than suckling or fattening pigs. Co-infection with PRRSV enforces clinical signs of PMWS, the influence of other viral co-infections is not clear. Vaccination against PCV2 significantly reduced viral co-infections in pigs.

Reliability of operational data from pig herds and performance ratings by veterinarians and pig farmers collected during telephone interviews for the evaluation of a PCV2 piglet vaccination.

BACKGROUND: The aim of the present study was to evaluate the feasibility of using a telephone survey in gaining an understanding of the possible herd and management factors influencing the performance (i.e. safety and efficacy) of a vaccine against porcine circovirus type 2 (PCV2) in a large number of herds and to estimate customers' satisfaction. RESULTS: Datasets from 227 pig herds that currently applied or have applied a PCV2 vaccine were analysed. Since 1-, 2- and 3-site production systems were surveyed, the herds were allocated in one of two subsets, where only applicable variables out of 180 were analysed. Group 1 was comprised of herds with sows, suckling pigs and nursery pigs, whereas herds in Group 2 in all cases kept fattening pigs. Overall 14 variables evaluating the subjective satisfaction with one particular PCV2 vaccine were comingled to an abstract dependent variable for further models, which was characterized by a binary outcome from a cluster analysis: good/excellent satisfaction (green cluster) and moderate satisfaction (red cluster). The other 166 variables comprised information about diagnostics, vaccination, housing, management, were considered as independent variables. In Group 1, herds using the vaccine due to recognised PCV2 related health problems (wasting, mortality or porcine dermatitis and nephropathy syndrome) had a 2.4-fold increased chance (1/OR) of belonging to the green cluster. In the final model for Group 1, the diagnosis of diseases other than PCV2, the reason for vaccine administration being other than PCV2-associated diseases and using a single injection of iron had significant influence on allocating into the green cluster (P < 0.05). In Group 2, only unchanged time or delay of time of vaccination influenced the satisfaction (P < 0.05). CONCLUSION: The methodology and statistical approach used in this study were feasible to scientifically assess "satisfaction", and to determine factors influencing farmers' and vets' opinion about the safety and efficacy of a new vaccine.

Clinical, virological, immunological and pathological evaluation of four porcine circovirus type 2 vaccines.

The objective of this study was to rigorously compare the efficacy of four porcine circovirus type 2 (PCV2) vaccines of varying antigen type and dose under experimental conditions based on well-defined clinical (average daily weight gain [ADWG]), virological (evidence of viraemia), immunological (presence of PCV2-specific neutralising antibodies [NA], interferon-γ-secreting cells [IFN-γ-SCs], and CD3(+) and CD4(+) T cell subsets), and pathological (lymphoid lesion and PCV2 antigen score) criteria. A total of 60, 3-week old piglets were assigned to six groups of 10/group and were vaccinated either with 1/4 commercially available one-dose vaccines or were not vaccinated. At 7 weeks of age, vaccinated and control animals were inoculated intranasally with 2 mL of PCV2b. All pigs were euthanased and subjected to post-mortem examination at 25 weeks of age. From 9 to 16 weeks of age, the ADWG of vaccinated animals was significantly higher than that of non-vaccinates. Significant (P<0.05) differences were observed between vaccinated and positive control groups in the quantity of log-transformed PCV2b DNA in the blood and nasal swabs, log-transformed NA titres, and PCV2-specific IFN-γ-SCs at 0, 7, 14, 21, and 42 days post challenge (dpc). The proportion of CD4(+) cells at 7 and 14 dpc was also significantly different between vaccinated and control pigs (P<0.05). The histopathological lesions and PCV2-antigen scores in the lymph nodes were significantly lower (P<0.05) in vaccinated animals. All four vaccines were found to be highly efficacious in controlling experimental PCV2 challenge based on this range of criteria.

Efficacy of a piglet-specific commercial inactivated vaccine against Porcine circovirus type 2 in clinical field trials.

The efficacy of a piglet-specific inactivated Porcine circovirus type 2 (PCV2) vaccine was evaluated with clinical field trials, as recommended by the Republic of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected on the basis of their history of postweaning multisystemic wasting syndrome. On each farm 60, 1-week-old pigs were randomly allocated to 1 of 2 treatment groups: vaccination at 1 and 3 wk of age or no vaccination. The 2-dose schedule of vaccination with inactivated PCV2 vaccine improved the average daily weight gain from birth to 16 wk of age, the PCV2 load in the blood, and the frequency and severity of lymph node lesions. Inactivated PCV2 vaccine seems to be very effective in controlling PCV2 infection under field conditions.

L'efficacité d'un vaccin spécifique pour les porcelets à base de circovirus porcin de type 2 (PCV2) a été évalué dans des études cliniques, tel que recommandé par l'Agence d'inspection et de quarantaine des animaux, plantes et des pêcheries de la République de la Corée. Trois fermes ont été sélectionnées en fonction de leur historique relativement au syndrome de dépérissement multi-systémique en période post-sevrage. Sur chaque ferme, 60 porcelets de 1 semaine d'âge ont été répartis de manière aléatoire à un des 2 groupes de traitement : vaccination à 1 et 3 semaine d'âge, ou aucune vaccination. La cédule de vaccination à 2 doses avec le vaccin PCV2 inactivé a amélioré le gain quotidien moyen entre la naissance et l'âge de 16 semaines, la charge sanguine de PCV2, ainsi que la fréquence et la sévérité des lésions des noeuds lymphatiques. Le vaccin PCV2 inactivé semble être très efficace pour maîtriser les infections par PCV2 dans des conditions de terrain.(Traduit par Docteur Serge Messier).

Effectiveness of porcine circovirus type 2 vaccination in reducing the severity of post-weaning multisystemic wasting syndrome in pigs.

Changes in the severity of post-weaning multisystemic wasting syndrome (PMWS) and the effect of vaccination against porcine circovirus type 2 (PCV2) on the severity of PMWS and the prevalence of PCV2 were assessed on 50 English pig farms from 2008 to 2010. PMWS severity on farms before and after PCV2 vaccination was estimated by combining data on post-weaning mortality, morbidity and proportion of pigs positive for PCV2 by PCR. At the first visit (before vaccination), all 50 farms were seropositive for PCV2 and 90% of farms were positive for PCV2 by PCR. At the second visit (331-539 days after the first visit), all 50 farms remained seropositive for PCV2 and 28/50 (56%) were positive for PCV2 by PCR, representing 16/36 (44.4%) farms that vaccinated against PCV2 and 12/14 (85.7%) farms that did not. There was a reduction of ~50% in mean PMWS score on farms that vaccinated and were initially moderately or highly PMWS affected. Vaccination against PCV2 reduced the severity of PMWS, even though PCV2 persisted on 44% of farms after vaccination.

Dynamics of antibody response and viraemia following natural infection of porcine circovirus 2 (PCV-2) in a conventional pig herd.

Porcine circovirus 2 (PCV-2) is a primary agent of post-weaning multi-systemic wasting syndrome (PMWS), ubiquitous in pig herds. The course of viraemia and seroconversion in naturally infected pigs were investigated in piglets from the 2nd week of their life. Piglets were divided into seropositive (Ab(+)) and seronegative (Ab(-)) groups. Subsequently, after vaccination against PCV-2 (Ingelvac(®) CIRCOFLEX™, Böehringer Ingelheim), they were further divided into non-vaccinated seronegative (NVAC/Ab(-)) and seropositive (NVAC/Ab(+)), and vaccinated seronegative (VAC/Ab(-)) and seropositive (VAC/Ab(+)). PCV-2 colostral antibodies failed to prevent development of natural PCV-2 infection in conventional piglets; however, this occurred at a higher age in comparison with seronegative pigs. Neither colostral nor post-infection antibodies prevented development of viraemia, which persisted up to the end of the study (the 19th week), but without clinical signs of PMWS. Vaccination failed to prevent development of natural PCV-2 infection, but viraemia was limited to between the 8th and 10th week. The presence of colostral anti-PCV-2 antibodies did not show any untoward effect to vaccination; on the contrary, VAC/Ab(+) animals showed the lowest titre of viraemia.

Cost of post-weaning multi-systemic wasting syndrome and porcine circovirus type-2 subclinical infection in England - an economic disease model.

Post-weaning multi-systemic wasting syndrome (PMWS) is a multi-factorial disease with major economic implications for the pig industry worldwide. The present study aimed to assess the economic impact of PMWS and porcine circovirus type 2 (PCV2) subclinical infections (PCV2SI) for farrow-to-finish farms and to estimate the resulting cost to the English pig industry. A disease model was built to simulate the varying proportions of pigs in a batch that get infected with PCV2 and develop either PMWS, subclinical disease (reduce growth without evident clinical signs) or remain healthy (normal growth and no clinical signs), depending on the farm level PMWS severity. This PMWS severity measure accounted for the level of post-weaning mortality, PMWS morbidity and proportion of PCV2 infected pigs observed on farms. The model generated six outcomes: infected pigs with PMWS that die (PMWS-D); infected pigs with PMWS that recover (PMWS-R); subclinical pigs that die (Sub-D); subclinical pigs that reach slaughter age (Sub-S); healthy pigs sold (H-S); and pigs, infected or non-infected by PCV2, that die due to non-PCV2 related causes (nonPCV2-D). Enterprise and partial budget analyses were used to assess the deficit/profits and the extra costs/extra benefits of a change in disease status, respectively. Results from the economic analysis at pig level were combined with the disease model's estimates of the proportion of different pigs produced at different severity scores to assess the cost of PMWS and subclinical disease at farm level, and these were then extrapolated to estimate costs at national level. The net profit for a H-S pig was £19.2. The mean loss for a PMWS-D pig was £84.1 (90% CI: 79.6-89.1), £24.5 (90% CI: 15.1-35.4) for a PMWS-R pig, £82.3 (90% CI: 78.1-87.5) for a Sub-D pig, and £8.1 (90% CI: 2.18-15.1) for a Sub-S pig. At farm level, the greatest proportion of negative economic impact was attributed to PCV2 subclinical pigs. The economic impact for the English pig industry for the year 2008, prior to the introduction of PCV2 vaccines, was estimated at £52.6 million per year (90% CI: 34.7-72.0), and approximately £88 million per year during the epidemic period. This was the first study to use empirical data to model the cost of PMWS/PCV2SI at different farm severity levels. Results from this model will be used to assess the efficiency of different control measures and to provide a decision support tool to farmers and policy makers.

Economic efficiency analysis of different strategies to control post-weaning multi-systemic wasting syndrome and porcine circovirus type 2 subclinical infection in 3-weekly batch system farms.

The study assessed the economic efficiency of different strategies for the control of post-weaning multi-systemic wasting syndrome (PMWS) and porcine circovirus type 2 subclinical infection (PCV2SI), which have a major economic impact on the pig farming industry worldwide. The control strategies investigated consisted on the combination of up to 5 different control measures. The control measures considered were: (1) PCV2 vaccination of piglets (vac); (2) ensuring age adjusted diet for growers (diets); (3) reduction of stocking density (stock); (4) improvement of biosecurity measures (bios); and (5) total depopulation and repopulation of the farm for the elimination of other major pathogens (DPRP). A model was developed to simulate 5 years production of a pig farm with a 3-weekly batch system and with 100 sows. A PMWS/PCV2SI disease and economic model, based on PMWS severity scores, was linked to the production model in order to assess disease losses. This PMWS severity scores depends on the combination post-weaning mortality, PMWS morbidity in younger pigs and proportion of PCV2 infected pigs observed on farms. The economic analysis investigated eleven different farm scenarios, depending on the number of risk factors present before the intervention. For each strategy, an investment appraisal assessed the extra costs and benefits of reducing a given PMWS severity score to the average score of a slightly affected farm. The net present value obtained for each strategy was then multiplied by the corresponding probability of success to obtain an expected value. A stochastic simulation was performed to account for uncertainty and variability. For moderately affected farms PCV2 vaccination alone was the most cost-efficient strategy, but for highly affected farms it was either PCV2 vaccination alone or in combination with biosecurity measures, with the marginal profitability between 'vac' and 'vac+bios' being small. Other strategies such as 'diets', 'vac+diets' and 'bios+diets' were frequently identified as the second or third best strategy. The mean expected values of the best strategy for a moderately and a highly affected farm were £14,739 and £57,648 after 5 years, respectively. This is the first study to compare economic efficiency of control strategies for PMWS and PCV2SI. The results demonstrate the economic value of PCV2 vaccination, and highlight that on highly affected farms biosecurity measures are required to achieve optimal profitability. The model developed has potential as a farm-level decision support tool for the control of this economically important syndrome.

[Economic impact of Circovac® - vaccination in a PCV2 subclinically infected farm in Switzerland on performance parameters]. / Ökonomische Auswirkungen der CIRCOVAC® - Impfung in einem subklinisch mit PCV2 infizierten Zuchtbetrieb in der Schweiz auf die Mastleistungsparameter.

Vaccination of dams in a PCV2 subclinically infected farm 2 and 4 weeks before insemination, with a booster at 12 weeks of gestation did not influence fertility parameters of the dams. However, growth parameters of offspring of vaccinated sows improved significantly (+ 51 g/d), resulting in a shorter growing period of 9 days and a massively improved economy. Mortality of weaners and fattening pigs was not significantly influenced by dam vaccination. Nevertheless, compared to a period of 6 months before vaccination, the mortality rate declined in the weaning period by 0,3 % and in the fattening period by 5,5 %. The Return on Investment (ROI) was calculated with 1:9.5. Even, the historically low pork prices in 2011 led to a ROI of 1:7.

Efficacy of a reformulated inactivated chimeric PCV1-2 vaccine based on clinical, virological, pathological and immunological examination under field conditions.

Inactivated chimeric porcine circovirus (PCV) 1-2 vaccine was initially taken off the market due to concerns that the vaccine virus was not killed and thus further replicated and spread in the pig population. In August 2011, a reformulated inactivated chimeric PCV1-2 vaccine re-entered the market. The efficacy of the reformulated inactivated chimeric PCV1-2 vaccine was evaluated under field conditions for registration as recommended by the Republic of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected based on their history of postweaning multisystemic wasting syndrome (PMWS). On each farm, a total of 50 3-week-old pigs were randomly allocated to one of two treatment groups: (i) vaccinated at 3 weeks of age and (ii) non-vaccinated. Clinical examination indicated that vaccinated animals displayed an improved average daily weight gain (672.2g/day vs. 625g/day; difference of +47.3g/day; P<0.05) and a reduced time to market (177 days vs. 183 days; difference of -6 days; P<0.05). Virological examination indicated that vaccinated animals displayed a reduced PCV2 load in the blood and nasal swabs compared to non-vaccinated animals. Pathological examination indicated that vaccination of pigs against PCV2 effectively reduced the number of PMWS-associated microscopic lesions and the PCV2 load in lymphoid tissues compared to non-vaccinated animals in the 3 herds. Immunological examination indicated that vaccinated animals induced PCV2-specific neutralizing antibodies (NA) and interferon-γ-secreting cells (IFN-γ-SCs). A reduction in the PCV2 load in the blood coincided with the appearance of both PCV2-specific NA and IFN-γ-SCs in the vaccinated animals. The number of CD4(+) cells was decreased in non-vaccinated animals compared to vaccinated animals. The reformulated inactivated chimeric PCV1-2 vaccine seems to be very effective in controlling PCV2 infection based on clinical, virological, pathological, and immunological evaluations under field conditions.

Commercial porcine circovirus type 2 vaccines: efficacy and clinical application.

Porcine circovirus type 2 (PCV2) is the one of the most economically important pathogens of pigs. After postweaning multisystemic wasting syndrome (PMWS) was first identified and reported in western Canada in 1991, it took 13years for the first commercial PCV2 vaccine to be used under special licence in France and Germany in 2004. Along with PMWS, PCV2 is also associated with a number of diseases and syndromes, collectively referred to as porcine circovirus-associated disease (PCVAD). Currently, five commercial vaccines are available on the international market. Commercial PCV2 vaccines were initially developed to control PMWS, but they are now also used against other PCVAD. This review focuses on (1) the types of commercial vaccines; (2) the criteria of vaccine efficacy; (3) the clinical, virological, immunological and pathological efficacy of the vaccines; and (4) the use of PCV2 vaccines against different clinical manifestations of PCVAD.