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Indian Journal of Microbiology logoLink to Indian Journal of Microbiology
. 2010 Mar 16;50(3):266–274. doi: 10.1007/s12088-010-0026-9

MVA recombinants expressing the fusion and hemagglutinin genes of PPRV protects goats against virulent challenge

Dev Chandran 1, Kolli Bhaktavatsala Reddy 1, Shahana Pallichera Vijayan 1, Parthasarthy Sugumar 1, Gudavalli Sudha Rani 1, Ponsekaran Santha Kumar 1, Lingala Rajendra 1, Villuppanoor Alwar Srinivasan 1,✉
PMCID: PMC3450065  PMID: 23100840

Abstract

Peste des Petits Ruminants (PPR) is a highly contagious animal disease caused by the Peste des Petits Ruminants virus (PPRV) belonging to the genus morbillivirus and family Paramyxoviridae. The disease results in high morbidity and mortality in goats, sheep and in some small wild ruminants. The presence of large number of small ruminants reared in endemic areas makes PPR a notorious disease threatening the livelihood of poor farmers. Conventional vaccination using a live, attenuated vaccine gives adequate protection but cannot be used in case of eradication of the disease due to difficulty in differentiation of infected animals from the vaccinated ones.

In the present study, we constructed two recombinant viruses using attenuated Modified Vaccinia virus Ankara virus (MVA) namely MVA-F and MVA-H expressing the full length PPRV fusion (F) and hemagglutinin (H) glycoproteins, respectively. Goats were vaccinated intramuscularly with 105 plaque forming units (PFU) each of the recombinant viruses and a live attenuated vaccine (RAKSHA PPR) and challenged 4 months later with PPRV challenge virus (103 goat LD50). All goats were completely protected from the clinical disease. This study gave an indication that mass vaccination of small ruminants with either of the above or both recombinant inexpensive virus vaccines could help in possible eradication of PPRV from endemic countries like India and subsequent seromonitoring of the disease for differentiation of infected animals from vaccinated ones.

Keyword: Morbillivirus, Peste des Petits Ruminants, PPRV, Recombinant MVA83, Fusion protein

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References

  • 1.Dhar P., Sreenivasa B.P., Barrett T., Corteyn M., Singh R.P., Bandyopadhyay S.K. Recent epidemiology of peste des petits ruminants virus PPRV. Vet Microbiol. 2002;88(2):153–159. doi: 10.1016/S0378-1135(02)00102-5. [DOI] [PubMed] [Google Scholar]
  • 2.Shaila M.S., Purushothaman V., Bhavasar D., Venugopal K., Venkatesan R.A. Peste des petits ruminants in India. Vet Rec. 1989;125(24):602–606. [PubMed] [Google Scholar]
  • 3.Kumar A., Singh S.V., Rana R., Vaid R.K., Misri J., Vihan V.S. PPR outbreak in goats: epidemiological and therapeutic studies. Indian J Anim Sci. 2001;71(9):815–818. [Google Scholar]
  • 4.Singh RP, Sreenivasa BP and Bandyopadhyay SK (2002) Prevalence and distribution of peste des petits ruminants PPR virus infection in small ruminants of India. In Proc Indian Society for Sheep and Goat Production and Utilization ISSGPU, 5th National Seminar on strength, challenges and opportunities in small ruminant diseases in new millennium, 30–31 December, Jaipur ISSGPU, Jaipur, pp 130–134
  • 5.Bandyopadhyay S.K. 14th annual conference and national seminar on management of viral diseases with emphasis on global trade and WTO regime, Indian Virological Society, 18–20 January, Hebbal, Bangalore. Hissar: Indian Virological Society; 2002. The economic appraisal of a PPR control programme in India. [Google Scholar]
  • 6.Diallo A., Minet C., Goff C., Berhe G., Albina E., Libeau G., Barett T. The threat of peste des petits ruminants: progress in vaccine development for disease control. Vaccine. 2007;25:5591–5597. doi: 10.1016/j.vaccine.2007.02.013. [DOI] [PubMed] [Google Scholar]
  • 7.Barrett T., Banyard A.C., Diallo A. Molecular biology of the morbilliviruses. In: Barrett T., Pastoret P.P., Taylor W.P., editors. In: Molecular biology of the morbillivirus. Amsterdam: Academic Press, Elsevier; 2005. pp. 31–67. [Google Scholar]
  • 8.Diallo A., Taylor W.P., Lef’evre P.C., Provost A. Att’enuation d’une souche de virus de la peste des petits ruminants: candidat pour un vaccine homologue. Rev Elev M’ed v’et Pays Trop. 1989;42:311–317. [PubMed] [Google Scholar]
  • 9.Tsukiyama T., Yoshikawa Y., Kamata H., Imaoka H., Asano K., Funahashi S., Maruyama T., Shida H., Sugimoto M., Yamanouchi K. Development of heat-stable recombinant rinderpest vaccine. Arch Virol. 1989;107:225–235. doi: 10.1007/BF01317919. [DOI] [PubMed] [Google Scholar]
  • 10.Stephensen C.B., Welter J., Thaker S.R., Taylor J., Tartaglia J., Paoletti E. Canine distemper virus CDV infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection. J Virol. 1997;71:1506–1513. doi: 10.1128/jvi.71.2.1506-1513.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Romero C.H., Barrett T., Evans S.A., Kitching R.P., Gershon P.D., Bostock C., Black D.N. Single capripoxvirus recombinant vaccine for the protection of cattle against rinderpest and lumpy skin disease. Vaccine. 1993;11:737–742. doi: 10.1016/0264-410X(93)90258-Y. [DOI] [PubMed] [Google Scholar]
  • 12.Romero C.H., Barrett T., Chamberlain R.W., Kitching R.P., Fleming M., Black D.N. Recombinant capripoxvirus expressing the haemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses. Virology. 1994;204:425–429. doi: 10.1006/viro.1994.1548. [DOI] [PubMed] [Google Scholar]
  • 13.Moss B. Genetically Engineered Poxviruses for Recombinant Gene Expression, Vaccination and Safety. PNAS USA. 1996;93:11341–11348. doi: 10.1073/pnas.93.21.11341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Mayr A (1967) Production of high quality interferons by means of strains of smallpox virus, which had been attenuated in cell culture passages. Zentralbl Bakteriol Mikrobiol Hyg Abt1 Orig B 183–190 [PubMed]
  • 15.Meyer H., Sutter G., Mayr A. Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. J Gen Virol. 1991;72:1031–1038. doi: 10.1099/0022-1317-72-5-1031. [DOI] [PubMed] [Google Scholar]
  • 16.Antoine G., Scheiflinger F., Dorner F., Falkner F.G. The Complete Genomic Sequence of the Modified Vaccinia Ankara Strain: Comparison with Other Orthopoxviruses. Virology. 1998;244:365–396. doi: 10.1006/viro.1998.9123. [DOI] [PubMed] [Google Scholar]
  • 17.Carroll M., Moss B. Host Range and Cytopathogenicity of the Highly Attenuated MVA Strain of Vaccinia Virus: Propagation and Generation of Recombinant Viruses in a Nonhuman Mammalian Cell Line. Virology. 1997;238:198–211. doi: 10.1006/viro.1997.8845. [DOI] [PubMed] [Google Scholar]
  • 18.Drexler I., Heller K., Wahren B., Erfle V., Sutter G. Highly attenuated modified vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus propagation, but not in various human transformed and primary cells. J Gen Virol. 1998;79:347–352. doi: 10.1099/0022-1317-79-2-347. [DOI] [PubMed] [Google Scholar]
  • 19.Blanchard T.J., Alcami A., Andrea P., Smith G.L. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol. 1998;79:1159–1167. doi: 10.1099/0022-1317-79-5-1159. [DOI] [PubMed] [Google Scholar]
  • 20.Sutter G., Moss B. Nonreplicating vaccinia vector efficiently expresses recombinant genes. PNAS USA. 1992;89:10847–10851. doi: 10.1073/pnas.89.22.10847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Moss B., Carroll M.W., Wyatt L.S., Bennink J.R., Hirsch V., Golstein S., Elkins W.R., Fuerst T.R., Lifson J.D., Piatak M., Restifo N.P., Overwijk W., Chamberlain R., Rosenberg S.A., Sutter G. Host range restricted non-replicating vaccinia virus vectors as vaccine candidates. Adv Exp Med Biol. 1996;397:7–13. doi: 10.1007/978-1-4899-1382-1_2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Stittelaar K.J., Kuiken T., Swart R.L., Amerongen G., Vos H.W., Niesters H.G., Schalkwijk P., Kwast T., Wyatt L.S., Moss B., Osterhaus A.D. Safety of modified vaccinia virus Ankara MVA in immune-suppressed macaques. Vaccine. 2001;19:3700–3709. doi: 10.1016/S0264-410X(01)00075-5. [DOI] [PubMed] [Google Scholar]
  • 23.Wyatt L.S., Earl P.L., Eller L.A., Moss B. Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge. PNAS USA. 2004;101:4590–4595. doi: 10.1073/pnas.0401165101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Hoover D.M., Lubkowski J. DNA Works: an automated method for designing oligonucleotides for PCRbased gene synthesis. Nucleic Acids Res. 2002;30(10):e43. doi: 10.1093/nar/30.10.e43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Wyatt L.S., Shors S.T., Murphy B.R., Moss B. Development of a replication-deficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model. Vaccine. 1996;14:1451–1458. doi: 10.1016/S0264-410X(96)00072-2. [DOI] [PubMed] [Google Scholar]
  • 26.Earl P.L., Moss B., Wyatt L.S., Carroll M.W. Current Protocols in Molecular Biology. In: Ausubel F.M., Brent R., Kingston R.E., Moore D.D., Seidman J.G., Smith J.A., Struhl K., editors. In: Current protocols in molecular biology. New York: Greene Publishing Associates and Wiley Interscience; 1998. pp. 16171–16191. [Google Scholar]
  • 27.Singh R.P., Sreenivasa B.P., Dhar P., Shah L.C., Bandyopadhyay S.K. Development of monoclonal antibody based competitive ELISA for detection and titration of antibodies to peste des petits ruminants PPR virus. Vet Microbiol. 2004;98(1):3–15. doi: 10.1016/j.vetmic.2003.07.007. [DOI] [PubMed] [Google Scholar]
  • 28.Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 1970;227:680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  • 29.Bassiri M.S., Ahmad L., Giavedoni L., Jones J.T., Saliki C.M., Yilma T. Immunological responses of mice and cattle to baculovirus expressed F and H proteins of rinderpest virus: lack of protection in the presence of neutralizing antibody. J Virol. 1993;67:1255–1261. doi: 10.1128/jvi.67.3.1255-1261.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Dhinakar R.G., Nachimuthu K., Mahalinga N.A. A simplified objective method for quantification of peste des petits ruminants virus or neutralizing antibody. J Virol Methods. 2000;89(1–2):89–95. doi: 10.1016/S0166-0934(00)00206-8. [DOI] [PubMed] [Google Scholar]
  • 31.OIE Manual of diagnostic tests and vaccines for Terrestrial animals (2006). Chapter 2.1.5. Website: http://www.oie.int/eng/Normes/mmanual/A_00028.htm.
  • 32.Cox W.I., Tartaglia J., Paoletti E. Poxvirus recombinants as live vaccines. In: Binns M.M., Smith G.L., editors. Recombinant poxviruses. Boca Raton, Florida: Recombinant Poxviruses CRC Press; 1992. pp. 23–162. [Google Scholar]
  • 33.The global eradication of smallpox Final report of the global commission for the certification of smallpox eradication History of international public health, No. 4. Geneva, Switzerland: World Health Organization; 1980. [Google Scholar]
  • 34.Miyahira Y., Garc’a-Sastre A., Rodriguez D., Rodriguez J.R., Murata K., Tsuji M., Palese P., Esteban M., Zavala F., Nussenzweig R.S. Recombinant viruses expressing a human malaria antigen elicit protective immune CD881 T cell responses in mice. PNAS USA. 1998;95:3954–3959. doi: 10.1073/pnas.95.7.3954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Coupar B.E., Andrew M.E., Both G.W., Boyle D.B. Temporal regulation of influenza haemagglutin expression in vaccinia virus recombinants and effects of the immune response. Eur J Immunol. 1986;16:1479–1487. doi: 10.1002/eji.1830161203. [DOI] [PubMed] [Google Scholar]
  • 36.Good R.A., Zak S.J. Disturbances in gamma globulin synthesis as “experiments of nature”. Pediatrics. 1956;18:109–114. [PubMed] [Google Scholar]
  • 37.Zhu Y., Rota P., Wyatt L., Tamin A., Rozenblatt S., Lerche N., Moss B., Bellini W., McChesney M. Evaluation of recombinant vaccinia virus measles vaccines in infant rhesus macaques with preexisting measles antibody. Virology. 2000;276:202–213. doi: 10.1006/viro.2000.0564. [DOI] [PubMed] [Google Scholar]
  • 38.Inui K., Barrett T., Kitching R.P., Yamanouchi K. Long-term immunity in cattle vaccinated with a recombinant rinderpest vaccine. Vet Rec. 1995;137:669–670. [PubMed] [Google Scholar]
  • 39.Ngichabe C.K., Wamwayi H.M., Barrett T., Ndungu E.K., Black D.N., Bostock C.J. Trial of a capripoxvirusrinderpest recombinant vaccine in African cattle. Epidemiol Infect. 1997;118:63–70. doi: 10.1017/S0950268896007200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Ohishi K., Inui K., Barrett T., Yamanouchi K. Longterm protective immunity to rinderpest in cattle following a single vaccination with a recombinant vaccinia virus expressing the virus haemagglutinin protein. J Gen Virol. 2000;81:1439–1446. doi: 10.1099/0022-1317-81-6-1439. [DOI] [PubMed] [Google Scholar]
  • 41.Verardi P.H., Aziz F.H., Ahmad S., Jones L.A., Beyene B., Ngotho R.N., Wamwayi H.M., Yesus M.G., Egziabher B.G., Yilma T.D. Long-term sterilizing immunity to rinderpest in cattle vaccinated with a recombinant vaccinia virus expressing high levels of the fusion and hemagglutinin glycoproteins. J Virol. 2002;76(2):484–491. doi: 10.1128/JVI.76.2.484-491.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Sreenivasa B.P., Dhar P., Singh R.P., Bandyopadhyay S.K. Proc 10th Annual Conference of the Indian Association of Veterinary Microbiologists, Immunologists and Specialists in Infectious Diseases, 14–16 October, Pantnagar, India. Pantnagar: GB Pant University of Agriculture and Technology; 2000. Evaluation of an indigenously developed homologous live-attenuated cell culture vaccine against peste des petits ruminants infection of small ruminants. [Google Scholar]

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