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Application of DIVA vaccines and their companion diagnostic tests to foreign animal disease eradication

  • John Pasick (a1)

The risk of foreign animal disease introduction continues to exist despite Canada's strict regulations concerning the importation of animals and animal products. Given the rapidity with which these diseases can spread, especially in areas with dense livestock populations, eradication efforts which rely solely on quarantine and stamping-out measures can present a formidable undertaking. This, combined with growing economic and ethical considerations, has led to renewed interest in the use of vaccination as a tool in controlling foreign animal disease outbreaks. Vaccination has effects at the individual and population levels. Efficacious vaccines reduce or prevent clinical signs without necessarily preventing virus replication. They may also increase the dose of virus needed to establish an infection and/or reduce the level and duration of virus shedding following infection. Vaccine effectiveness within a population is a function of its ability to reduce virus transmission. Transmission is best described by the reproductive ratio, R, which is defined as the average number of new infections caused by one infectious individual. By helping to reduce the R-value below 1, vaccination can be an effective adjunct in abbreviating an outbreak. Nevertheless, vaccination can also complicate serological surveillance activities that follow eradication, if the antibody response induced by vaccination is indistinguishable from that which follows infection. This disadvantage can be overcome by the use of DIVA vaccines and their companion diagnostic tests. The term DIVA (differentiating infected from vaccinated individuals) was coined in 1999 by J. T. van Oirschot of the Central Veterinary Institute, in the Netherlands. It is now generally used as an acronym for ‘differentiating infected from vaccinated animals’. The term was originally applied to the use of marker vaccines, which are based on deletion mutants of wild-type microbes, in conjunction with a differentiating diagnostic test. The DIVA strategy has been extended to include subunit and killed whole-virus vaccines. This system makes possible the mass vaccination of a susceptible animal population without compromising the serological identification of convalescent individuals. The DIVA approach has been applied successfully to pseudorabies and avian influenza eradication, and has been proposed for use in foot-and-mouth disease and classical swine fever eradication campaigns. This paper will survey current vaccine technology, the host immune response, and companion diagnostic tests that are available for pseudorabies, foot-and-mouth disease, classical swine fever and avian influenza.

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Aggarwal, N and Barnett, PV (2002). Antigenic sites of foot-and-mouth disease virus (FMDV): an analysis of the specificities of anti-FMDV antibodies after vaccination of naturally susceptible hosts. Journal of General Virology 83: 775782.
Ahrens, U, Kaden, V, Drexler, C and Visser, N (2000). Efficacy of the classical swine fever (CSF) marker vaccine Porcilis Pesti in pregnant sows. Veterinary Microbiology 77: 8397.
Alexandersen, S, Zhang, Z, Kitching, RP and Donaldson, AI (2001). Overview of the FMDV carrier problem. In: EU Workshop. Persistence of Foot-and-Mouth Disease Virus and the Risk of Carrier Animals, June 28–29 2001, Lelystad, The Netherlands.
Bergmann, IE, de Mello, PA, Neitzert, E, Beck, E and Gommes, I (1993). Diagnosis of persistent aphthovirus infection and its differentiation from vaccination response in cattle by use of enzyme-linked immunoelectrotransfer blot analysis with bioengineered nonstructural viral antigens. American Journal of Veterinary Research 54: 825831.
Biront, P, Leunen, J and Vandeputte, J (1987). Inhibition of virus replication in the tonsils of pigs previously vaccinated with a Chinese strain vaccine and challenged oronasally with a virulent strain of classical swine fever virus. Veterinary Microbiology 14: 105113.
Bouma, A, de Smit, AJ, de Kluijver, EP, Terpstra, C and Moormann, RJM (1999). Efficacy and stability of a subunit based on glycoprotein E2 of classical swine fever virus. Veterinary Microbiology 66: 101114.
Capua, I, Terregino, C, Cattoli, G, Mutinelli, F and Rodriguez, JF (2002). Development of a DIVA (differentiating infected from vaccinated animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza. Avian Pathology 32: 4755.
Chung, W-B, Sorensen, KJ, Liao, P-C, Yang, P-C, Jong, M-H (2002). Differentiation of foot-and-mouth disease virus-infected from vaccinated pigs by enzyme-linked immunosorbent assay using nonstructural protein 3AB as the antigen and application to an eradication program. Journal of Clinical Microbiology 40: 28432848.
de Smit, AJ, Bouma, A, de Kluijver, EP, Terpstra, C and Moormann, RJM (2000). Prevention of transplacental transmission of moderate-virulent classical swine fever virus after single or double vaccination with E2 subunit vaccine. Veterinary Quarterly 22: 150153.
de Smit, AJ, Bouma, A, van Gennip, HG, de Kluijver, EP and Moormann, RJ (2001a). Chimeric (marker) C-strain viruses induce clinical protection against virulent classical swine fever virus (CSFV) and reduce transmission of CSFV between vaccinated pigs. Vaccine 19: 14671476.
de Smit, AJ, Bouma, A, de Kluijver, EP, Terpstra, C and Moormann, RJM (2001b). Duration of the protection of an E2 subunit marker vaccine against classical swine fever after a single vaccination. Veterinary Microbiology 78: 307317.
Diekmann, O, Heesterbeek, JAP and Metz, AJ (1990). On the definition and the computation of the basic reproductive ratio R 0 in models for infectious diseases in heterogenous populations. Journal of Mathematical Biology 28: 365382.
Donaldson, AI and Kitching, RP (1989). Transmission of foot and mouth disease by vaccinated cattle following natural challenge. Research in Veterinary Science 46: 914.
Dewulf, J, Laevens, H, Koenen, F, Mintiens, K and de Kruif, A (2003). A comparative study for emergency vaccination against CSF with an E2 subunit vaccine and a C-strain vaccine. Vaccine Preventive Veterinary Medicine 65: 121133.
Floegel-Niesmann, G (2001). Classical swine fever (CSF) marker vaccine trial III. Evaluation of discriminatory ELISAs. Veterinary Microbiology 83: 121136.
Halvorson, DA (2002). The control of H5 and H7 mildly pathogenic avian influenza: a role for inactivated vaccine. Avian Pathology 31: 512.
Hammond, JM, McCoy, RJ, Jansen, ES, Morrissy, CJ, Hodgson, ALM and Johnson, MA (2000). Vaccination of a single dose of a recombinant porcine adenovirus expressing the classical swine fever virus gp55 (E2) gene protects pigs against classical swine fever. Vaccine 18: 10401050.
Hammond, JM, Jansen, ES, Morrisy, CJ, Williamson, MM, Hodgson, ALM and Johnson, MA (2001). Oral and sub-cutaneous vaccination of commercial pigs with a recombinant porcine adenovirus expressing the classical swine fever virus gp55 gene. Archives of Virology 146: 17871793.
Kinker, DR, Swenson, SL, Wu, LL and Zimmerman, JJ (1997). Evaluation of serological tests for the detection of pseudorabies gE antibodies during early infection. Veterinary Microbiology 55: 99106.
Lorena, J, Barlic-Maganja, D, Lojkic, M, Madic, J, Grom, J, Cac, Z, Roic, B, Terzic, S, Lojkic, I, Polancec, D and Cajavec, S (2001). Classical swine fever virus (C strain) distribution in organ samples of inoculated piglets. Veterinary Microbiology 81: 18.
Mackay, DKJ, Forsyth, MA, Davies, PR, Berlinzani, A, Belsham, GJ, Flint, M and Ryan, MD (1998). Differentiating infection from vaccination in foot-and-mouth disease using a panel of recombinant, non-structural proteins in ELISA. Vaccine 16: 446459.
Mettenleiter, TC (2000). Aujeszky's disease (pseudorabies) virus: the virus and molecular pathogenesis—state of the art, June 1999. Veterinary Research 31: 99115.
Meuwissen, MPM, Horst, SH, Huirne, RBH and Dijkhuizen, AA (1999). A model to estimate the financial consequences of classical swine fever outbreaks: principles and outcomes. Preventive Veterinary Medicine 42: 249270.
Neitzert, E, Beck, E, de Mello, PA, Gommes, I and Bergmann, IE (1991). Expression of the aphthovirus RNA polymerase gene in Escherichia coli and its use together with other bioengineered nonstructural antigens in detection of late persistent infections. Virology 184: 799805.
Ozaki, H, Sugiura, T, Sugita, S, Imagawa, H and Kida, H (2001). Detection of antibodies to the nonstructural protein (NS1) of influenza A virus allows distinction between vaccinated and infected horses. Veterinary Microbiology 82: 111119.
Qiaohua, W, Moraes, MP and Grubman, MJ (2003). Recombinant adenovirus co-expressing capsid proteins of two serotypes of foot-and-mouth disease virus (FMDV): in vitro characterization and induction of neutralizing antibodies against FMDV in swine. Virus Research 93: 211219.
Sørensen, KJ, Madsen, KG, Madsen, ES, Salt, JS, Nqindi, J and Mackay, DK (1998). Differentiation of infection from vaccination in foot-and-mouth disease by the detection of antibodies to the non-structural proteins 3D, 3AB and 3ABC in ELISA using antigens expressed in baculovirus. Archives of virology 143: 14611476.
Stegeman, A (1995). Pseudorabies virus eradication by area-wide vaccination is feasible. Veterinary Quarterly 17: 150156.
Stegeman, A, Elbers, ARW, Bouma, A, de Smit, H and de Jong, MCM (1999a). Transmission of classical swine fever virus within herds during the 1997–1998 epidemic in the Netherlands. Preventive Veterinary Medicine 42: 201218.
Stegeman, A, Elbers, ARW, Smak, J and de Jong, MCM (1999b). Quantification of the transmission of classical swine fever virus between herds during the 1997–1998 epidemic in the Netherlands. Preventive Veterinary Medicine 42: 219234.
Stettler, P, Devos, R, Moser, C, Tratschin, J-D and Hofmann, MA (2002). Establishment and application of bicistronic classical swine fever virus genomes for foreign gene expression and complementation of E2 deletion mutants. Virus Research 85: 173185.
Swayne, DE, Perdue, ML, Beck, JR, Garcia, M and Suarez, DL (2000). Vaccines protect chickens against H5 highly pathogenic avian influenza in the face of genetic changes in field viruses over multiple years. Veterinary Microbiology 74: 165172.
van Gennip, HGP, van Rijn, PA, Widjojoatmodjo, MN, de Smit, AJ and Moormann, RJM (2001). Chimeric classical swine fever viruses containing envelope protein E RNS or E2 of bovine viral diarrhea virus protects pigs against challenge with CSFV and induce a distinguishable antibody response. Vaccine 19: 447459.
van Gennip, HGP, Bouma, A, van Rijn, PA, Widjojoatmodjo, MN and Moormann, RJM (2002). Experimental non-transmissible marker vaccines for classical swine fever (CSF) by trans -complementation of E rns or E2 of CSFV. Vaccine 20: 15441556.
van Oirschot, JT (1992). Properties of gI-negative vaccines and companion diagnostic tests for the eradication of Aujeszky's disease. In: Proceedings of the 96th Annual Meeting of the USA Animal Health AssociationLouisville. pp. 405416
van Oirschot, JT (1999). Diva vaccines that reduce virus transmission. Journal of Biotechnology 73: 195205.
van Oirschot, JT, Gielkens, ALJ, Moormann, RJM and Berns, AJM (1990). Marker vaccines, virus protein-specific antibody assays and the control of Aujeszky's disease. Veterinary Microbiology 23: 85101.
van Oirschot, JT, Kaashoek, MJ, Rijsewijk, FAM and Stegeman, JA (1996). The use of marker vaccines in eradication of herpesviruses. Journal of Biotechnology 44: 7581.
van Rijn, PA, Miedema, GKW, Wensvoort, G, van Gennip, HGP and Moormann, RJM (1994). Antigenic structure of envelope glycoprotein E1 of hog cholera virus. Journal of Virology 68: 39343942.
van Rijn, PA, Bossers, A, Wensvoort, G and Moormann, RJM (1996). Classical swine fever virus (CSFV) envelope glycoprotein E2 containing one structural antigenic unit protects pigs from lethal CSFV challenge. Journal of General Virology 77: 27372745.
Wang, CY, Chang, TY, Walfield, AM, Ye, J, Shen, M, Chen, SP, Li, MC, Lin, YL, Jong, MH, Yang, PC, Chyr, N, Kramer, E and Brown, F (2002). Effective synthetic peptide vaccine for foot-and-mouth disease in swine. Vaccine 20: 26032610.
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Animal Health Research Reviews
  • ISSN: 1466-2523
  • EISSN: 1475-2654
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