Identification and characterization of mimotopes of classical swine fever virus E2 glycoprotein using specific anti-E2 monoclonal antibodies
Batonick, M. ; Loeffen, W.L.A. ; Metwally, S.A. ; Mayr, G.A. - \ 2013
Virus Research 175 (2013)1. - ISSN 0168-1702 - p. 12 - 19.
hog-cholera virus - random peptide library - phage display library - viral-diarrhea-virus - b-cell epitope - linear epitope - disease virus - e-rns - diagnosis - protein
Classical swine fever virus (CSFV) shares high nucleic acid and amino acid sequence homology with the other members of the pestivirus genus, namely bovine viral diarrhea virus and border disease virus. All three viruses are able to infect swine and generate cross reactive antibodies, which is problematic during differential diagnosis for classical swine fever (CSF). Toward the development of a new generation of CSF specific diagnostic tools, monoclonal antibodies specific for CSFV were mapped using phage display technology. Six mimotopes were identified, some of which were found to be antigenic and/or specific for CSF when used as coating antigens in an ELISA for the detection of CSF antibodies in swine serum. Two mimotopes in particular termed V2-2 and V7-1 recognized numerous strains of CSF antisera and bound fewer BVD and BD antisera compared to a commercial CSF antibody ELISA. These two mimotopes may be useful to the pestivirus field in the development of a highly specific CSF antibody ELISA as well as in the development of other potential diagnostic technologies.
Preliminary mapping of non-conserved epitopes on envelope glycoprotein E2 of bovine viral diarrhea virus type 1 and 2
Jelsma, H. ; Loeffen, W.L.A. ; Beuningen, A.R. van; Rijn, P.A. van - \ 2013
Veterinary Microbiology 166 (2013)1-2. - ISSN 0378-1135 - p. 195 - 199.
swine-fever virus - random peptide library - hog-cholera virus - b-cell epitope - monoclonal-antibodies - strain brescia - vaccines - protein - identification - neutralization
Bovine viral diarrhea virus (BVDV) belongs together with Classical swine fever virus (CSFV) and Border disease virus (BDV) to the genus Pestivirus in the Flaviviridae family. BVDV has been subdivided into two different species, BVDV1 and BVDV2 based on phylogenetic analysis. Subsequent characterization of both strains revealed major antigenic differences. Because the envelope glycoprotein E2 is the most immunodominant protein for all pestiviruses, the present study focused on epitope mapping by constructing chimeric BVDV type 1 and 2 E2 genes in expression plasmids. These plasmids with chimeric E2-genes were transfected in SK6 cells and transient expression was studied by immunostaining with a panel of MAbs specific for E2 of BVDV1 or BVDV2, resulting in the localization of type-specific antigenic domains at similar regions. These results indicate that E2 glycoproteins of both BVDV types exhibit a comparable antigenic structure, but with type specific epitopes. In addition, the antigenic resemblance with envelope glycoprotein E2 of Classical swine fever virus is discussed.
Efficacy of chimeric Pestivirus vaccine candidates against Classical Swine Fever: protection and DIVA characteristics
Eble, P.L. ; Geurts, Y. ; Quak, J. ; Moonen-Leusen, H.W.M. ; Blome, S. ; Hofmann, M.A. ; Koenen, F. ; Beer, M. ; Loeffen, W.L.A. - \ 2013
Veterinary Microbiology 162 (2013)2-4. - ISSN 0378-1135 - p. 437 - 446.
subunit marker vaccine - hog-cholera virus - monoclonal-antibodies - pigs - transmission - differentiation - strains - infection - virulent - induce
Currently no live DIVA (Differentiating Infected from Vaccinated Animals) vaccines against classical swine fever (CSF) are available. The aim of this study was to investigate whether chimeric pestivirus vaccine candidates (CP7_E2alf, Flc11 and Flc9) are able to protect pigs against clinical signs, and to reduce virus shedding and virus transmission, after a challenge with CSF virus (CSFV), 7 or 14 days after a single intramuscular vaccination. In these vaccine candidates, either the E2 or the Erns encoding genome region of a bovine viral diarrhoea virus strain were combined with a cDNA copy of CSFV or vice versa. Furthermore, currently available serological DIVA tests were evaluated. The vaccine candidates were compared to the C-strain. All vaccine candidates protected against clinical signs. No transmission to contact pigs was detected in the groups vaccinated with C-strain, CP7_E2alf and Flc11. Limited transmission occurred in the groups vaccinated with Flc9. All vaccine candidates would be suitable to stop on-going transmission of CSFV. For Flc11, no reliable differentiation was possible with the current Erns-based DIVA test. For CP7_E2alf, the distribution of the inhibition percentages was such that up to 5% false positive results may be obtained in a large vaccinated population. For Flc9 vaccinated pigs, the E2 ELISA performed very well, with an expected 0.04% false positive results in a large vaccinated population. Both CP7_E2alf and Flc9 are promising candidates to be used as live attenuated marker vaccines against CSF, with protection the best feature of CP7_E2alf, and the DIVA principle the best feature of Flc9.
Rational design of a classical swine fever C-strain vaccine virus that enables the differentiation between infected and vaccinated animals
Kortekaas, J.A. ; Vloet, R.P.M. ; Weerdmeester, K. ; Ketelaar, J.H.E. ; Eijk, M. van; Loeffen, W.L.A. - \ 2010
Journal of Virological Methods 163 (2010)2. - ISSN 0166-0934 - p. 175 - 185.
hog-cholera virus - csf marker vaccine - e-rns - envelope glycoprotein-e1 - structural glycoprotein - monoclonal-antibodies - protects swine - e2 - pestivirus - challenge
The C-strain of the classical swine fever virus (CSFV) is considered the gold standard vaccine for the control of CSF. This vaccine, however, does not enable the serological differentiation between infected and vaccinated animals (DIVA). Consequently, its use can impose severe trade restrictions. The immunodominant and evolutionarily conserved A-domain of the E2 structural glycoprotein is an important target in CSFV-specific ELISAs. With the ultimate aim to render the C-strain suitable as a DIVA vaccine, mutations were introduced that were expected to dampen the immunogenicity of the A-domain. In the first of two approaches, the feasibility of shielding the A-domain by N-linked glycans was evaluated, whereas in the second approach C-strain mutants were created with targeted deletions in the A-domain. Analysis of the antibody responses elicited in rabbits suggested that shielding of the A-domain by an N-linked glycan had a minor effect on the immune response against the A-domain, whereas a targeted deletion of only a single amino acid severely dampened this response. C-strain mutants with larger deletions were highly debilitated and incapable of sustained growth in vitro. By providing the viruses with the opportunity to increase their fitness by mutation, a mutant was rescued that found a way to compensate for the imposed fitness cost. Most of the identified mutations occurred in several independently evolved viruses, demonstrating parallel evolution. By virtue of this compensatory evolution, a well replicating and genetically stable C-strain mutant was produced that can be serologically differentiated from wildtype CSFV. The findings provide the molecular basis for the development of a novel, genetically stable, live attenuated CSF DIVA vaccine.
The effect of tissue degradation on detection of infectious virus and viral RNA to diagnose classical swine fever virus
Weesendorp, E. ; Willems, E.M. ; Loeffen, W.L.A. - \ 2010
Veterinary Microbiology 141 (2010)3-4. - ISSN 0378-1135 - p. 275 - 281.
hog-cholera virus - rt-pcr - wild boar - epidemiology - netherlands - performance - outbreak - disease
A considerable part of tissue samples that are collected for the monitoring of classical swine fever (CSF) from the wild boar population or from domestic pigs are unsuitable for virus detection using the fluorescent antibody test (FAT) or virus isolation (VI), due to tissue degradation. Reverse transcription polymerase chain reaction (RT-PCR) has a higher sensitivity than the FAT and VI, and is supposed to be less sensitive to sample degradation. Reliable and quantitative information on how long viral RNA and infectious virus can be detected in organs and which organs are most susceptible to degradation is, however, lacking. In the present study we generated survival curves of infectious CSF virus (CSFV) and viral RNA in the tonsil, mesenteric lymph node, spleen and kidney, obtained from 24 pigs infected with a moderately virulent CSFV strain. Tissue samples were stored at room temperature and tested by VI and RT-PCR, directly after storage and 1, 2, 3, 4, 7, 14 and 21 days later. It was shown that the RT-PCR is not only more sensitive than VI on fresh tissue samples, but RT-PCR is also less vulnerable to sample degradation. Average half-life values of viral RNA in the tissues ranged from 0.95 to 2.55 days, while half-life values of infectious virus ranged from 0.21 to 0.31 days. The tonsil and spleen are regarded as the most appropriate organs for the detection of infectious virus and viral RNA, not only in fresh samples, but also in samples that suffer from tissue degradation
Dynamics of virus excretion via different routes in pigs experimentally infected with classical swine fever virus strains of high, moderate or low virulence
Weesendorp, E. ; Stegeman, A. ; Loeffen, W.L.A. - \ 2009
Veterinary Microbiology 133 (2009)1-2. - ISSN 0378-1135 - p. 9 - 22.
hog-cholera virus - subunit vaccine - transmission - pathogenesis - epidemiology - netherlands - antibodies - efficacy - signs
Classical swine fever virus (CSFV) is transmitted via secretions and excretions of infected pigs. The efficiency and speed of the transmission depends oil a multitude of parameters, like quantities Of Virus excreted by infected Pigs. ThiS study provides quantitative data oil excretion of CSFV over time front pigs infected with a highly, moderately or low virulent strain. For each strain. five individually housed pigs were infected. Virus excretion was quantified in oropharyngeal fluid, saliva, nasal fluid, lacrimal fluid, faeces, urine and skin scraping by virus titration and quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRRT-PCR). Infectious virus Was excreted in all secretions and excretions of Pigs infected with the highly and moderately virulent strain, while excretion front pigs infected with the low virulent strain was mostly restricted to the oronasal route. Pigs infected with the highly virulent strain excreted significantly more virus in all their secretions and excretions over the entire infectious period than pigs infected with the moderately or low virulent strains. An exception were the pigs that developed the chronic form of infection after inoculation with the moderately virulent strain. During the entire infectious period, they excreted the largest amounts of virus via most secretions and excretions, as they excreted virus continuously and for a long duration. This study highlights the crucial role chronically infected pigs may play in the transmission of CSFV. Furthermore, it demonstrates the importance of discriminating between strains and the clinical appearance of infection When using excretion data for modelling.
A review of RT-PCR technologies used in veterinary virology and disease control: sensitive and specific diagnosis of five livestock diseases notifiable to the World Organisation for Animal Health
Hoffmann, B. ; Beer, M. ; Reid, S.M. ; Mertens, P. ; Oura, C.A.L. ; Rijn, P.A. van; Slomka, M.J. ; Banks, J. ; Brown, I.H. ; Alexander, D.J. ; King, D.P. - \ 2009
Veterinary Microbiology 139 (2009)1-2. - ISSN 0378-1135 - p. 1 - 23.
polymerase-chain-reaction - foot-and-mouth - classical-swine-fever - real-time pcr - reverse-transcription-pcr - avian influenza-viruses - resonance energy-transfer - hog-cholera virus - internal positive control - mediated isothermal amplification
Real-time, reverse transcription polymerase chain reaction (rRT-PCR) has become one of the most widely used methods in the field of molecular diagnostics and research. The potential of this format to provide sensitive, specific and swift detection and quantification of viral RNAs has made it an indispensable tool for state-of-the-art diagnostics of important human and animal viral pathogens. Integration of these assays into automated liquid handling platforms for nucleic acid extraction increases the rate and standardisation of sample throughput and decreases the potential for cross-contamination. The reliability of these assays can be further enhanced by using internal controls to validate test results. Based on these advantageous characteristics, numerous robust rRT-PCRs systems have been developed and validated for important epizootic diseases of livestock. Here, we review the rRT-PCR assays that have been developed for the detection of five RNA viruses that cause diseases that are notifiable to the World Organisation for Animal Health (OIE), namely: foot-and-mouth disease, classical swine fever, bluetongue disease, avian influenza and Newcastle disease. The performance of these tests for viral diagnostics and disease control and prospects for improved strategies in the future are discussed.
Survival of classical swine fever virus at various temperatures in faeces and urine derived from experimentally infected pigs
Weesendorp, E. ; Stegeman, A. ; Loeffen, W.L.A. - \ 2008
Veterinary Microbiology 132 (2008)3-4. - ISSN 0378-1135 - p. 249 - 259.
hog-cholera virus - aujeszkys-disease - european-union - epidemiology - transmission - inactivation - netherlands - pathogenesis - diagnosis - outbreak
Indirect transmission of classical swine fever virus (CSFV) can occur through contact with mechanical vectors, like clothing and footwear or transport vehicles, contaminated with the secretions or excretions of infected pigs. A prerequisite for indirect transmission is survival of the virus on the mechanical vector. Consequently, to obtain more insight into these transmission routes, it is important to know how long the virus remains viable outside the host. In this study we examined the survival of classical swine fever virus in faeces and urine derived from pigs intranasally inoculated with a highly or moderately virulent CSFV strain. Faeces and urine were collected between days 5 and 36 post-inoculation, and stored at 5, 12, 20, and 30 °C. Next, the virus titres were determined in the samples by virus titration, and a random selection of these samples was also analyzed by quantitative real-time reverse transcription polymerase chain reaction (qRRT-PCR) to determine the viral RNA decay. Survival curves were generated, and it was shown that the inactivation rate was inversely related to the storage temperature. Average half-life values were between 2 and 4 days at 5 °C, and between 1 and 3 h at 30 °C. Significant differences were observed in survival between virus strains in faeces, however, not in urine. The reduction in viral RNA during the entire study period was limited. This study provided detailed information on survival of CSFV in excretions of infected pigs, which can be used to improve control measures or risk-analysis models
A common neutralizing epitope on envelope glycoprotein E2 of different pestiviruses: Implications for improvement of vaccines and diagnostics for classical swine fever (CSF)?
Rijn, P.A. van - \ 2007
Veterinary Microbiology 125 (2007)39479. - ISSN 0378-1135 - p. 150 - 156.
viral diarrhea virus - hog-cholera virus - monoclonal-antibodies - e-rns - fetal protection - marker vaccines - subunit vaccine - linear epitope - strain brescia - protein
The Pestivirus genus within the family of Flaviviridae consists of at least three species; classical swine fever virus (CSFV) found in swine and wild boar, bovine viral diarrhoea virus type 1 and type 2 (BVDV-I and BVDV-II) mainly isolated from cattle and border disease virus (BDV) preferably replicating in ovine species. Many features demonstrate differences between CSFV and other pestiviruses, BVDV-I, BVDV-II and BDV, here defined as nonCSFV, whereas other features show similarities between all different species of pestiviruses. Focussing on the major envelope glycoprotein E2, the immunodominant protein of pestiviruses, CSFV seems to be a more distinct species within the Pestivirus genus. Here we confirm on one hand the more separated grouping of CSFV by isolation of monoclonal antibodies (MAbs) raised against E2 of BVDV-I and BVDV-II. None of these MAbs recognize E2 of CSFV strains. On the other hand, only one MAb, MAb 912, was isolated against E2 of BDV. MAb 912 binds to E2 of CSFV strains and partly neutralizes CSFV. The epitope of MAb 912 is mapped in antigenic domain B of CSFV-E2. This common epitope of CSFV strains and nonCSFV strains could have implications for development of DIVA vaccines and serological diagnostics for CSF.
Limited BVDV transmission and full protection against CSFV transmission in pigs experimentally infected with BVDV type 1b
Wieringa-Jelsma, H. ; Quak, J. ; Loeffen, W.L.A. - \ 2006
Veterinary Microbiology 118 (2006)1-2. - ISSN 0378-1135 - p. 26 - 36.
viral diarrhea virus - classical swine-fever - hog-cholera virus - monoclonal-antibodies - neutralizing antibody - vaccine - signs - epidemiology - inoculation - challenge
Bovine viral diarrhea virus (BVDV) in pigs may interfere with the detection and epidemiology of classical swine fever virus (CSFV). To investigate the importance of BVDV infections in pigs, first we studied the transmission dynamics of a recent BVDV field isolate. Subsequently, the protection of BVD antibodies against transmission and clinical disease of CSF virus was studied. Only limited transmission of BVDV occurred (R = 0.20), while no CSFV transmission occurred in pigs with BVDV antibodies. We concluded that BVDV transmission among pigs is possible, but seems to be limited and thus the virus should disappear from a population if no new introductions occur. Furthermore, the presence of BVD antibodies may completely prevent the transmission of CSFV and therefore could protect pigs against classical swine fever. It was also noticed that double infections with BVDV and CSFV were incorrectly diagnosed using the neutralization peroxidase linked assay (NPLA), which is the golden standard for antibody detection. This might hamper the diagnosis of CSF in herds with a high BVD prevalence
Dimerisation of glycoprotein E(rns) of classical swine fever virus is not essential for viral replication and infection
Gennip, H.G.P. van; Hesselink, A.T. ; Moormann, R.J.M. ; Hulst, M.M. - \ 2005
Archives of Virology 150 (2005)11. - ISSN 0304-8608 - p. 2271 - 2286.
hog-cholera virus - pestivirus e-rns - heparan-sulfate - diarrhea virus - strain brescia - rnase activity - insect cells - identification - establishment - ribonuclease
The pestivirus glycoprotein Erns, a ribonuclease, is expressed on the surface of virions and in infected cells as a disulfide-linked homodimer. Erns is involved in the infection process and its RNase activity is probably involved in viral replication and pathogenesis. The most C-terminal cysteine residue forms an intermolecular disulfide bond with another Erns monomer, resulting in an Erns dimer. To study the function of dimerisation of Erns for viral replication, the cysteine residue at amino acid position 438 was mutated into a serine residue. The mutated C438S gene was cloned into a vector containing an infectious cDNA copy of the CSFV C-strain genome. Using reverse genetics, a mutant virus was generated that only expressed monomeric Erns, confirming that Cys 438 is essential for homodimerisation. Characterization of this mutant virus and of a baculovirus-expressed C438S mutant protein indicated that the loss of the dimeric state of Erns reduced the affinity of binding of virions and Erns to heparan sulphate (HS), the receptor for Erns on the cell surface of SK6 cells. This suggests that interaction of virus-bound Erns homodimers with membrane associated HS may be a joined action of the two HS-binding domains (one in each monomer) present in the homodimer.
Identification of classical swine fever virus protein E2 as a target for cytotoxic T cells by using mRNA-transfected antigen-presenting cells
Ceppi, M. ; Bruin, M.G.M. de; Seuberlich, T. ; Balmelli, C. ; Pascolo, S. ; Tratschin, J.D. ; Ruggli, N. ; Wienhold, D. ; Summerfield, A. - \ 2005
Journal of General Virology 86 (2005)9. - ISSN 0022-1317 - p. 2525 - 2534.
hog-cholera virus - mhc class-i - dendritic cells - monoclonal-antibodies - cancer-immunotherapy - nucleotide-sequence - pseudorabies virus - protective value - marker vaccines - lymphocytes
Vaccination of pigs against Classical swine fever virus (CSFV) by using live-virus vaccines induces early protection before detectable humoral immune responses. Immunological analyses indicate that this is associated with T-cell activation, underlining the importance of targeting cytotoxic T-lymphocyte (CTL) responses for vaccine improvement. Antigen-presenting cells (APCs) transfected with mRNA encoding structural protein E2 or non-structural viral proteins NS3¿NS4A were used to identify viral genes encoding CTL epitopes. Monocyte-derived dendritic cells (DCs) and fibrocytes served as the APCs. In vitro translation of the mRNA and microscopic analysis of transfected cells demonstrated that E2 and NS3¿NS4A could be identified. APCs transfected with either of the mRNA molecules restimulated CSFV-specific T cells to produce gamma interferon and specific cytotoxic activity against CSFV-infected target cells. The presence of CTL epitopes on E2 was confirmed by using d/d-haplotype MAX cells expressing E2 constitutively as target cells in d/d-haplotype CTL assays. A potent CTL activity against E2 was detected early (1¿3 weeks) after CSFV challenge. This work corroborates the existence of CTL epitopes within the non-structural protein domain NS3¿NS4A of CSFV. Furthermore, epitopes on the E2 protein can also now be classified as targets for CTLs, having important implications for vaccine design, especially subunit vaccines. As for the use of mRNA-transfected APCs, this represents a simple and efficient method to identify viral genes encoding CTL epitopes in outbred populations
Interaction of classical swine fever virus with dendritic cells
Carrasco, C.P. ; Rigden, R.C. ; Vincent, I.E. ; Balmelli, C. ; Ceppi, M. ; Bauhofer, O. ; Tache, V. ; Hjertner, B. ; McNeilly, F. ; Gennip, H.G.P. van; McCullough, K.C. ; Summerfield, A. - \ 2004
Journal of General Virology 85 (2004). - ISSN 0022-1317 - p. 1633 - 1641.
viral diarrhea virus - double-stranded-rna - hog-cholera virus - full-length cdna - langerhans cells - bone-marrow - immune-response - infectious rna - apoptosis - pathogenesis
Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte- and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-/TNF- or polyinosinic¿polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN- responses in these DCs and even suppressed pIC-induced IFN- induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF- were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation.
Determinants of virulence of classical swine fever virus strain Brescia
Gennip, H.G.P. van; Vlot, A.C. ; Hulst, M.M. ; Smit, A.J. de; Moormann, R.J.M. - \ 2004
Journal of Virology 78 (2004)16. - ISSN 0022-538X - p. 8812 - 8823.
hog-cholera virus - viral diarrhea virus - glycoprotein e-rns - full-length cdna - protein e-rns - nucleotide-sequence - monoclonal-antibodies - heparan-sulfate - envelope protein-e1 - molecular-cloning
Two related classical swine fever virus (CSFV) strain Brescia clones were isolated from blood samples from an infected pig. Virus C1.1.1 is a cell-adapted avirulent variant, whereas CoBrB is a virulent variant. Sequence analysis revealed 29 nucleic acid mutations in C1.1.1, resulting in 9 amino acid substitutions compared to the sequence of CoBrB 476R. Using reverse genetics, parts of the genomes of these viruses, which contain differences that lead to amino acid changes, were exchanged. Animal experiments with chimeric viruses derived from C1.1.1 and CoBrB 476R showed that a combination of amino acid changes in the structural and nonstructural regions reduced the virulence of CSFV in pigs. Moreover, the presence of a Leu at position 710 in structural envelope protein E2 seemed to be an important factor in the virulence of the virus. Changing the Leu at position 710 in the CoBrB 476S variant into a His residue did not affect virulence. However, the 710His in the C1.1.1/CoBrB virus, together with adaptive mutations 276R, 476R, and 477I in Erns, resulted in reduced virulence in pigs. These results indicated that mutations in Erns and E2 alone do not determine virulence in pigs. The results of in vitro experiments suggested that a high affinity for heparan sulfate of C1.1.1 Erns may reduce the spread of the C1.1.1/CoBrB virus in pigs and together with the altered surface structure of E2 caused by the 710LH mutation may result in a less efficient infection of specific target cells in pigs. Both these features contributed to the attenuation of the C1.1.1/CoBrB virus in vivo.
Vaccinology of classical swine fever: from lab to field
Oirschot, J.T. van - \ 2003
Veterinary Microbiology 96 (2003)4. - ISSN 0378-1135 - p. 367 - 384.
hog-cholera virus - csf marker vaccine - c-strain virus - envelope glycoprotein e2 - protein e-rns - subunit vaccine - oral immunization - chinese strain - pseudorabies virus - aujeszkys-disease
There are two types of classical swine fever vaccines available: the classical live and the recently developed E2 subunit vaccines. The live Chinese strain vaccine is the most widely used. After a single vaccination, it confers solid immunity within a few days that appears to persist lifelong. The E2 subunit vaccine induces immunity from approximately 10¿14 days after a single vaccination. The immunity may persist for more than a year, but is then not complete. The Chinese strain vaccine may establish a strong herd immunity 1¿2 weeks earlier than the E2 vaccine. The ability of the Chinese vaccine strain to prevent congenital infection has not been reported, but the E2 subunit vaccine does not induce complete protection against congenital infection. Immunological mechanisms that underlie the protective immunity are still to be elucidated. Both types of vaccine are considered to be safe. A great advantage of the E2 subunit vaccine is that it allows differentiation of infected pigs from vaccinated pigs and is referred to as a DIVA vaccine. However, the companion diagnostic Erns ELISA to actually make that differentiation should be improved. Many approaches to develop novel vaccines have been described, but none of these is likely to result in a new DIVA vaccine reaching the market in the next 5¿10 years. Countries where classical swine fever is endemic can best control the infection by systematic vaccination campaigns, accompanied by the normal diagnostic procedures and control measures. Oral vaccination of wild boar may contribute to lowering the incidence of classical swine fever, and consequently diminishing the threat of virus introduction into domestic pigs. Free countries should not vaccinate and should be highly alert to rapidly diagnose any new outbreak. Once a new introduction of classical swine fever virus in dense pig areas has been confirmed, an emergency vaccination programme should be immediately instituted, for maximum benefit. The question is whether the time is ripe to seriously consider global eradication of classical swine fever virus.
Neighbourhood infections of classical swine fever during the 1997-1998 epidemic in the Netherlands
Crauwels, A.P.P. ; Nielen, M. ; Elbers, A.R.W. ; Stegeman, J.A. ; Tielen, M.J.M. - \ 2003
Preventive Veterinary Medicine 61 (2003). - ISSN 0167-5877 - p. 263 - 277.
hog-cholera virus - antibody-response - transmission - disease - herds - diptera - pigs - area
Data of the 1997-1998 epidemic of classical swine fever (CSF) in The Netherlands were analysed in survival analysis to identify risk factors that were associated with the rate of neighbourhood infections. The study population consisted of herds within 1000 m of exclusively one previously infected herd. Dates of virus introduction into herds were drawn randomly from estimated probability distributions per herd of possible weeks of virus introduction. (To confirm the insensitivity of the results for this random data-selection procedure, the procedure was repeated 9 times (resulting in 10 different datasets).) The dataset had 906 non-infected and 59 infected neighbour herds, which were distributed over 215 different neighbourhoods. Neighbour herds that never became infected were right-censored at the last date of the infectious period of the infected source herd. Neighbour herds that became empty within the infectious period or within the following 21 days due to preventive depopulation or due to the implemented buying-out programme were right-censored 21 days before the moment of becoming empty. This was done as a correction for the time a herd could be infected without being noticed as such. The median time to identified infection of neighbour herds was 2 weeks, whereas the median time to right censoring of non-infected neighbour herds was 3 weeks. The risk factors, radial distance less than or equal to500 m, cattle present on source herd and increasing herd size of the neighbour herd were associated multivariably with the hazard for neighbour herds to become infected. We did not find an association between time down wind and-infection risk for neighbour herds. Radial dispersion of CSFV seemed more important in neighbourhood infections than dispersion along the road on which the infected source herd is situated. The results of this study support the strategy of preventive depopulation in the neighbourhood of an infected herd. Recommendations are presented to adapt the applied control strategy for neighbourhood infections. (C) 2003 Elsevier B.V. All rights reserved.