, Volume 29, Issue 3, pp 285–296 | Cite as

An overview of process intensification and thermo stabilization for upscaling of Peste des petits ruminants vaccines in view of global control and eradication

  • Mousumi Bora
  • Raja Wasim Yousuf
  • Pronab Dhar
  • Rabindra Prasad Singh
Review Article


Peste des petits ruminants (PPR) has been recognized as a globally distributed disease affecting the small ruminant population. The disease results in severe economic losses mainly to small land holders and low input farming systems. The control of PPR is mainly achieved through vaccination with available live attenuated vaccines. The thermo labile nature of PPR virus poses a major constraint in production of quality vaccines which often results in vaccine failures. The lack of quality vaccine production jeopardize the wide vaccination coverage especially in countries with poor infrastructure due to which PPR persists endemically. The vaccine production system may require augmentation to attain consistent and quality vaccines through efforts of process intensification integrated with suitable stabilizer formulations with appropriate freeze drying cycles for improved thermo tolerance. Manufacturing of live attenuated PPR vaccines during batch cultures might introduce defective interfering particles (DIPs) as a result of high multiplicity of infection (MOI) of inoculums, which has a huge impact on virus dynamics and yield. Accumulation of DIPs adversely affects the quality of the manufactured vaccines which can be avoided through use of appropriate MOI of virus inoculums and quality control of working seed viruses. Therefore, adherence to critical manufacturing standard operating procedures in vaccine production and ongoing efforts on development of thermo tolerant vaccine will help a long way in PPR control and eradication programme globally. The present review focuses on the way forward to achieve the objectives of quality vaccine production and easy upscaling to help the global PPR control and eradication by mass vaccination as an important tool.


PPR Process intensification Defective interfering (DI) particles Thermo stability Upscaling 



The authors would like to acknowledge the Director, ICAR-IVRI, Joint Director Research and Joint Director (Academic) for the facilities to carry out this work. The authors would like to acknowledge the funding from the Department of Biotechnology (Grant No. BT/IM/Indo-UK/FADH/50/GDR/2013).


  1. 1.
    Alkeev N, Averin S, von Gratowski S. New method for monitoring the process of freeze drying of biological materials. AAPS PharmSciTech. 2015;16(6):1474–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Asim M, Rashid A, Chaudhary AH. Effect of various stabilizers on titre of lyophilized live-attenuated peste des petits ruminants (PPR) vaccine. Pak Vet J. 2008;28(4):203–4.Google Scholar
  3. 3.
    Aunins JG, Bader B, Caola A, Griffiths J, Katz M, Licari P, Ram K, Ranucci CS, Zhou W. Fluid mechanisms, cell distribution and environment in cellcube bioreactors. Biotechnol Prog. 2003;19:2–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Aunins JG. Viral vaccine production in cell culture. In: Encyclopedia of cell technology. 2003.Google Scholar
  5. 5.
    Bailey D, Banyard A, Dash P, Ozkul A, Barrett T. Full genome sequence of peste des petits ruminants virus, a member of the Morbillivirus genus. Virus Res. 2005;110(1):119–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Banyard AC, Parida S, Batten C, Oura C, Kwiatek O, Libeau G. Global distribution of peste des petits ruminants virus and prospects for improved diagnosis and control. J Gen Virol. 2010;91(12):2885–97.CrossRefPubMedGoogle Scholar
  7. 7.
    Barrett T, Banyard, AC, Diallo A. Rinderpest and peste des petits ruminants virus: plague of large and small ruminants. In: Barrett T, Pastoret P-P, Taylor WP, editors, Molecular biology of the morbillivirus: biology of animal infections. Academic Press: London; 2006. p. 31–67.Google Scholar
  8. 8.
    Bazarghani TT, Charkhkar S, Doroudi J, Bani Hassan E. A review on peste des petits ruminants (PPR) with special reference to PPR in Iran. Zoonoses Public Health. 2006;53(1):17–8.Google Scholar
  9. 9.
    Bourdin P, Laurent Vautier A. Note sur la structure du virus de la peste des petits ruminants. Revue d’élevage et de médecine vétérinaire des pays tropicaux. 1967;20(3):383–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Butler M. Growth limitations on microcarriers. Adv Biochem Eng Biotechnol. 1987;34:57–84.PubMedGoogle Scholar
  11. 11.
    Calain PH, Roux LA. Generation of measles virus defective interfering particles and their presence in a preparation of attenuated live-virus vaccine. J Virol. 1988;62(8):2859–66.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Cheng SC, Fischman HR. Lapinized Rinderpest virus and its use as a vaccine. In: Kesteven KVL, editor. Rinderpest Vaccines their production and use in the field. Washington: Food and Agriculture Organization of the United Nations; 1949. p. 47.Google Scholar
  13. 13.
    Chisti Y, Moo-Young M. Bioprocess intensification through bioreactor engineering. Chem Eng Res Des. 1996;74:575–83.Google Scholar
  14. 14.
    Diallo A, Barrett T, Lefevre PC, Taylor WP. Comparison of proteins induced in cells infected with rinderpest and peste des petits ruminants viruses. J Gen Virol. 1987;68(7):2033–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Dhar P, Bandyopadhyay SK. Defective interfering particles of morbillivirus: a review. Indian J Virol. 1999;15(1):1–5.Google Scholar
  16. 16.
    El-Bagoury GF, El-Nahas EM, Hussein AM, Mohamed AM. Assesment of two stabilizers used for lyophilized live attenuated peste des petits ruminants (PPR) vaccine. Behna Vet Med J. 2015;29(1):183–8.Google Scholar
  17. 17.
    EMPRES Transboundary Animal Diseases Bulletin. Peste des petits ruminants. FAO Animal Production and Health Division; 2012.Google Scholar
  18. 18.
    Enden G, Zhang YH, Merchuk JC. A model of the dynamics of insect cell infection at low multiplicity of infection. J Theor Biol. 2005;237(3):257–64.CrossRefPubMedGoogle Scholar
  19. 19.
    Epstein DA, Herman RC, Chien I, Lazzarini RA. Defective interfering particle generated by internal deletion of the vesicular stomatitis virus genome. J Virol. 1980;33(2):818–29.PubMedPubMedCentralGoogle Scholar
  20. 20.
    FAO O. Global strategy for the control and eradication of PPR. FAO and OIE. 2015.Google Scholar
  21. 21.
    Frensing T, Heldt FS, Pflugmacher A, Behrendt I, Jordan I, Flockerzi D, Genzel Y, Reichl U. Continuous influenza virus production in cell culture shows a periodic accumulation of defective interfering particles. PLoS ONE. 2013;8(9):e72288.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Frensing T, Pflugmacher A, Bachmann M, Peschel B, Reichl U. Impact of defective interfering particles on virus replication and antiviral host response in cell culture-based influenza vaccine production. Appl Microbiol Biotechnol. 2014;98(21):8999–9008.CrossRefPubMedGoogle Scholar
  23. 23.
    Galazka A, Milstien J, Zaffran M. Thermostability of vaccines. In: Global programmer for vaccines and inmunization. Geneva: WHO; 1998.Google Scholar
  24. 24.
    Gallo-Ramirez LE, Nikolay A, Genzel Y, Reichl U. Bioreactor concepts for cell culture-based viral vaccine production. Expert Rev Vaccines. 2015;14(9):1181–95.PubMedGoogle Scholar
  25. 25.
    Grein TA, Weidner T, Czermak P. Concepts for the production of viruses and viral vectors in cell culture. In: GowderSJT, editor. New Insights into Cell Culture Technology. 2017. ISBN: 978-953-51-3134-2.
  26. 26.
    Gubbay O, Curran J, Kolakofsky D. Sendai virus genome synthesis and assembly are coupled: a possible mechanism to promote viral RNA polymerase processivity. J Gen Virol. 2001;82(12):2895–903.CrossRefPubMedGoogle Scholar
  27. 27.
    Hamdy FM, Dardiri AH. Response of white-tailed deer to infection with peste des petits ruminants virus. J Wildl Dis. 1976;4:516–22.CrossRefGoogle Scholar
  28. 28.
    Harrison MS, Sakaguchi T, Schmitt AP. Paramyxovirus assembly and budding: building particles that transmit infections. Int J Biochem Cell Biol. 2010;42(9):1416–29.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Huang AS, Greenawalt JW, Wagner RR. Defective T particles of vesicular stomatitis virus: preparation, morphology, and some biologic properties. Virology. 1966;30(2):161–72.CrossRefPubMedGoogle Scholar
  30. 30.
    Johnson RH. Rinderpest in tissue culture. III: use of the attenuated strain as a vaccine for cattle. Br Vet J. 1962;118(4):141–50.CrossRefGoogle Scholar
  31. 31.
    Kim CH, Dummer DM, Chiou PP, Leong JA. Truncated particles produced in fish surviving infectious hematopoietic necrosis virus infection: mediators of persistence? J Virol. 1999;73(1):843–9.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Kirkwood TB, Bangham CR. Cycles, chaos, and evolution in virus cultures: a model of defective interfering particles. Proc Natl Acad Sci. 1994;91(18):8685–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Kumru OS, Joshi SB, Smith DE, Middaugh CR, Prusik T, Volkin DB. Vaccine instability in the cold chain: mechanisms, analysis and formulation strategies. Biologicals. 2014;42(5):237–59.CrossRefPubMedGoogle Scholar
  34. 34.
    Kwiatek O, Minet C, Grillet C, Hurard C, Carlsson E, Karimov B, Albina E, Diallo A, Libeau G. Peste des petits ruminants (PPR) outbreak in Tajikistan. J Comp Pathol. 2007;136(2):111–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Lamb RA, Krug RM. Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM, Fields BN, editors. Fields virology. Philadelphia: Lippincott-Raven Press; 1996.Google Scholar
  36. 36.
    Lancaster MU, Hodgetts SI, Mackenzie JS, Urosevic N. Characterization of defective viral RNA produced during persistent infection of Vero cells with Murray Valley encephalitis virus. J Virol. 1998;72(3):2474–82.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Li D, Lott WB, Lowry K, Jones A, Thu HM, Aaskov J. Defective interfering viral particles in acute dengue infections. PLoS ONE. 2011;6(4):e19447.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Mahapatra M, Parida S, Egziabher BG, Diallo A, Barrett T. Sequence analysis of the phosphoprotein gene of peste des petits ruminants (PPR) virus: editing of the gene transcript. Virus Res. 2003;96(1):85–98.CrossRefPubMedGoogle Scholar
  39. 39.
    Mahapatra M, Parida S, Baron MD, Barrett T. Matrix protein and glycoproteins F and H of Peste-des-petits-ruminants virus function better as a homologous complex. J Gen Virol. 2006;87(7):2021–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Malik KP, Duru C, Ahmed M, Matejtschuk P. LYO/TITRATION: analytical options for the measurement of residual moisture content in lyophilized biological materials. Am Pharm Rev. 2010;13(5):42–7.Google Scholar
  41. 41.
    Mariner JC, House JA, Sollod AE, Stem C, Van den Ende M, Mebus CA. Comparison of the effect of various chemical stabilizers and lyophilization cycles on the thermostability of a Vero cell-adapted rinderpest vaccine. Vet Microbiol. 1990;21(3):195–209.CrossRefPubMedGoogle Scholar
  42. 42.
    Mariner JC, Gachanja J, Tindih SH, Toye P. A thermostable presentation of the live, attenuated peste des petits ruminants vaccine in use in Africa and Asia. Vaccine. 2017; 35(30):3773–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Martrenchar A, Zoyem N, Diallo A. Experimental study of a mixed vaccine against peste des petits ruminants and capripox infection in goats in northern Cameroon. Small Rumin Res. 1997;26(1–2):39–44.CrossRefGoogle Scholar
  44. 44.
    McLain L, Armstrong SJ, Dimmock NJ. One defective interfering particle per cell prevents influenza virus-mediated cytopathology: an efficient assay system. J Gen Virol. 1988;69(6):1415–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Mühlebach MD, Leonard VH, Cattaneo R. The measles virus fusion protein transmembrane region modulates availability of an active glycoprotein complex and fusion efficiency. J Virol. 2008;82(22):11437–45.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Munir M, editor. Mononegaviruses of veterinary importance, volume 1: pathobiology and molecular diagnosis, vol. 1. Wallingford: CABI; 2013.Google Scholar
  47. 47.
    Munir M, Zohari S, Berg M. Molecular biology and pathogenesis of peste des petits ruminants virus. Berlin: Springer; 2012.Google Scholar
  48. 48.
    Muniraju M, Munir M, Parthiban AR, Banyard AC, Bao J, Wang Z, Ayebazibwe C, Ayelet G, El Harrak M, Mahapatra M, Libeau G. Molecular evolution of peste des petits ruminants virus. Emerg Infect Dis. 2014;20(12):2023–33.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Muthuchelvan D, Rajak KK, Ramakrishnan MA, Choudhary D, Bhadouriya S, Saravanan P, Pandey AB, Singh RK. Peste-des-petits-ruminants: an Indian perspective. Adv Anim Vet Sci. 2015;3(8):422–9.CrossRefGoogle Scholar
  50. 50.
    Nguyen-Ba-Luong DN, Vu-Thien-Thai. Contribution to the study of the virus-vaccine against rinderpest, strain Nakamura III. Bull Off Int Epiz. 1958;50:559–63.Google Scholar
  51. 51.
    Ohtake S, Lechuga‐Ballesteros D, Truong‐Le V, Patzer EJ. Strategies for heat-stable vaccines. In: Wen EP, Ellis R, Pujar NS, editors. Vaccine Development and Manufacturing. 2015. p. 287–318.Google Scholar
  52. 52.
    Palaniswami KS, Thangavelu A, Velmurugan R. Development of thermostable peste des petits ruminants (PPR) virus vaccine and assessment of molecular changes in the F gene. In: Applications of gene-based technologies for improving animal production and health in developing countries. 2005. p. 673–678.Google Scholar
  53. 53.
    Parida S, Muniraju M, Mahapatra M, Muthuchelvan D, Buczkowski H, Banyard AC. Peste des petits ruminants. Vet Microbiol. 2015;181(1):90–106.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Pastorino B, Baronti C, Gould EA, Charrel RN, De Lamballerie X. Effect of chemical stabilizers on the thermostability and infectivity of a representative panel of freeze dried viruses. PLoS ONE. 2015;10(4):e0118963.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Patel SM, Nail SL, Pikal MJ, Geidobler R, Winter G, Hawe A, Davagnino J, Gupta SR. Lyophilized drug product cake appearance: what is acceptable? J Pharm Sci. 2017;106(7):1706–21.CrossRefPubMedGoogle Scholar
  56. 56.
    Pathak KB, Nagy PD. Defective interfering RNAs: foes of viruses and friends of virologists. Viruses. 2009;1(3):895–919.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Petric M, Prevec L. Vesicular stomatitis virus-A new interfering particle, intracellular structures, and virus-specific RNA. Virology. 1970;41(4):615–30.CrossRefPubMedGoogle Scholar
  58. 58.
    Plotkin S, Robinson JM, Cunningham G, Iqbal R, Larsen S. The complexity and cost of vaccine manufacturing—An overview. Vaccine. 2017;35(33):4064–71.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Plowright W, Ferris RD. Studies with rinderpest virus in tissue culture. III. The stability of cultured virus and its use in virus neutralization tests. Archiv fur die gesamte Virusforschung. 1962;11:516–33.CrossRefPubMedGoogle Scholar
  60. 60.
    Plowright W, Rampton CS, Taylor WP, Herniman KA. Studies on rinderpest culture vaccine. III. Stability of the lyophilised product. Res Vet Sci. 1970;11:71–81.PubMedGoogle Scholar
  61. 61.
    Roeder P, Mariner J, Kock R. Rinderpest: the veterinary perspective on eradication. Philos Trans R Soc B. 2013;368(1623):20120139.CrossRefGoogle Scholar
  62. 62.
    Rima BK, Davidson WB, Martin SJ. The role of defective interfering particles in persistent infection of Vero cells by measles virus. J Gen Virol. 1977;35(1):89–97.CrossRefPubMedGoogle Scholar
  63. 63.
    Riyesh T, Balamurugan V, Sen A, Bhanuprakash V, Venkatesan G, Yadav V, Singh RK. Evaluation of efficacy of stabilizers on the thermostability of live attenuated thermo-adapted Peste des petits ruminants vaccines. Virol Sin. 2011;26(5):324–37.CrossRefPubMedGoogle Scholar
  64. 64.
    Santhamani R, Singh RP, Njeumi F. Peste des petits ruminants diagnosis and diagnostic tools at a glance: perspectives on global control and eradication. Arch Virol. 2016;161(11):2953–67.CrossRefPubMedGoogle Scholar
  65. 65.
    Saravanan P, Sen A, Balamurugan V, Rajak KK, Bhanuprakash V, Palaniswami KS, Nachimuthu K, Thangavelu A, Dhinakarraj G, Hegde R, Singh RK. Comparative efficacy of peste des petits ruminants (PPR) vaccines. Biologicals. 2010;38(4):479–85.CrossRefPubMedGoogle Scholar
  66. 66.
    Sarkar J, Sreenivasa BP, Singh RP, Dhar P, Bandyopadhyay SK. Comparative efficacy of various chemical stabilizers on the thermostability of a live-attenuated Peste des petits ruminants (PPR) vaccine. Vaccine. 2003;21(32):4728–35.CrossRefPubMedGoogle Scholar
  67. 67.
    Schlehuber LD, McFadyena IJ, Shua Y, Carignana J, Paul Duprexa W, Forsytha WR, Hoa JH, Kitsos CM, Lee GY, Levinsona DA, Lucier SC, Moorea CB, Nguyena NT, Ramos J, André Weinstocka B, Zhang J, Monaglea JA, Gardner CR, Alvarez JC. Towards ambient temperature-stable vaccines: the identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay. Vaccine. 2011;29:5031–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Schlesinger S.  Retroviruses, Viroids, and RNA recombination. In: Domingo E, Holland JJ, Ahlquist P, editors. RNA Genetics. Vol II. Boca Raton: CRC Press; 1987, p. 167–185.Google Scholar
  69. 69.
    Scott GR. Thermal reactions of kenya cattle vaccinated with lapinized rinderpest virus. Nature. 1954;174(4418):44.CrossRefPubMedGoogle Scholar
  70. 70.
    Scott PD, Meng B, Marriott AC, Easton AJ, Dimmock NJ. Defective interfering influenza virus confers only short-lived protection against influenza virus disease: evidence for a role for adaptive immunity in DI virus-mediated protection in vivo. Vaccine. 2011;29(38):6584–91.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Sen A. Development and evaluation of a thermostable Peste des petits ruminants (PPR) vaccine using heavy water (D2O). Ph.D. Thesis. Division of Virology, Indian Veterinary Research Institute (IVRI); 2009.Google Scholar
  72. 72.
    Sen A, Saravanan P, Balamurugan V, Rajak KK, Sudhakar SB, Bhanuprakash V, Parida S, Singh RK. Vaccines against peste des petits ruminants virus. Expert Rev Vaccines. 2010;9(7):785–96.CrossRefPubMedGoogle Scholar
  73. 73.
    Shaikh FY, Crowe JE Jr. Molecular mechanisms driving respiratory syncytial virus assembly. Futur Microbiol. 2013;1:123–31.CrossRefGoogle Scholar
  74. 74.
    Shaila MS, Shamaki D, Forsyth MA, Diallo A, Goatley L, Kitching RP, Barrett T. Geographic distribution and epidemiology of Peste des petits ruminants viruses. Virus Res. 1996;143(2):149–53.CrossRefGoogle Scholar
  75. 75.
    Silva AC, Carrondo MJ, Alves PM. Strategies for improved stability of Peste des petits ruminants vaccine. Vaccine. 2011;29(31):4983–91.CrossRefPubMedGoogle Scholar
  76. 76.
    Silva AC, Yami M, Libeau G, Carrondo MJ, Alves PM. Testing a new formulation for Peste des petits ruminants vaccine in Ethiopia. Vaccine. 2014;32(24):2878–81.CrossRefPubMedGoogle Scholar
  77. 77.
    Singh RP, Saravanan P, Sreenivasa BP, Singh RK, Bandyopadhyay SK. Prevalence and distribution of Peste des petits ruminants virus infection in small ruminants in India. Rev Sci Tech. 2004;23(3):807–19.CrossRefPubMedGoogle Scholar
  78. 78.
    Singh RP, Bandyopadhyay SK. Peste des petits ruminants vaccine and vaccination in India: sharing experience with disease endemic countries. VirusDisease. 2015;26(4):215–24.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Spier MR, de Vandenberghe LPS, Medeiros ABP, Soccol CR. Application of different types of bioreactors in bioprocesses. In: Antolli PG, Liu Z, editors. Bioreactors: design, properties and applications. Nova Science Publishers Inc: New York; 2011. p. 55–90. ISBN 978-1-62100164-5.Google Scholar
  80. 80.
    Sreenivasa BP, Dhar P, Singh RP. Bandyopadhyay SK. Evaluation of an indigenously developed homologous live attenuated cell culture vaccine against Peste-des-petits-ruminants infection of small ruminants. In: Proceedings of XX annual conference of indian association of veterinary microbiologists, immunologists and specialists in infectious diseases (IAVMI), Pantnagar, Uttaranchal, India. 2000. p.84.Google Scholar
  81. 81.
    Tapia F, Vázquez-Ramírez D, Genzel Y, Reichl U. Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production. Appl Microbiol Biotechnol. 2016;100(5):2121–32.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Thompson KA, Rempala GA, Yin J. Multiple-hit inhibition of infection by defective interfering particles. J Gen Virol. 2009;90(4):888–99.CrossRefGoogle Scholar
  83. 83.
    Thompson KAS, Yin J. Population dynamics of an RNA virus and its defective interfering particles in passage cultures. Virology. 2010;7:257.CrossRefGoogle Scholar
  84. 84.
    Timm C, Akpinar F, Yin J. Quantitative characterization of defective virus emergence by deep sequencing. J Virol. 2014;88(5):2623–32.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Trabelsi K, Majoul S, Rourou S, Kallel H. Process intensification for an enhanced replication of a newly adapted RM-65 sheep pox virus strain in Vero cells grown in stirred bioreactor. Biochem Eng J. 2014;90:131–9.CrossRefGoogle Scholar
  86. 86.
    Trablesi K, Majoul S, Rourou S, Kallel H. Development of a measles vaccine production process in MRC-5 cells grown on Cytodex1 microcarriers and in a stirred bioreactor. Appl Microbiol Biotechnol. 2012;93:1031–40.CrossRefGoogle Scholar
  87. 87.
    Vazquez D, Genzel Y, Pieler MM, Jordan I, Sandig V, Reichl U. Intensification of MVA and influenza virus production through high-cell-density cultivation approaches. In: Vaccine Technology VI, Laura Palomares, UNAM, Mexico Manon Cox, Protein Sciences Corporation, USA Tarit Mukhopadhyay, University College London, UK Nathalie Garçon, BIOASTER Technology Research Institute, FR Eds, ECI Symposium Series. 2016.Google Scholar
  88. 88.
    Vincent S, Gerlier D, Manié SN. Measles virus assembly within membrane rafts. J Virol. 2000;74(21):9911–5.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Wertz GW, Perepelitsa VP, Ball LA. Gene rearrangement attenuates expression and lethality of a nonsegmented negative strand RNA virus. Proc Natl Acad Sci. 1998;95(7):3501–6.CrossRefPubMedGoogle Scholar
  90. 90.
    Whistler T, Bellini WJ, Rota PA. Generation of defective interfering particles by two vaccine strains of measles virus. Virology. 1996;220:480–4.CrossRefPubMedGoogle Scholar
  91. 91.
    Williams ES, Morales NM, Wasik BR, Brusic V, Whelan SP, Turner PE. Repeatable population dynamics among vesicular stomatitis virus lineages evolved under high co-infection. Front Microbiol. 2016;7(370):1–10Google Scholar
  92. 92.
    Willenbrink W, Neubert WJ. Long-term replication of Sendai virus defective interfering particle nucleocapsids in stable helper cell lines. J Virol. 1994;68(12):8413–7.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Worrall EE, Litamoi JK, Seck BM, Ayelet G. Xerovac: an ultra rapid method for the dehydration and preservation of live attenuated Rinderpest and Peste des Petits ruminants vaccines. Vaccine. 2000;19(7):834–9.CrossRefPubMedGoogle Scholar
  94. 94.
    Xue H, Yang B, Kristensen DD, Chen D. A freeze-stable formulation for DTwP and DTaP vaccines. Hum Vaccines Immunother. 2014;10(12):3607–10.CrossRefGoogle Scholar
  95. 95.
    Yaqub T, Shahid MF, Munir M, Ali M, Mukhtar N, Adid M. Comparative efficacy of stabilizers on the thermostability of Peste des petits Ruminants vaccine. J Vaccines Vaccin. 2016;7:6.CrossRefGoogle Scholar
  96. 96.
    Yoon SW, Lee SY, Won SY, Park SH, Park SY, Jeong YS. Characterization of homologous defective interfering RNA during persistent infection of Vero cells with Japanese encephalitis virus. Mol Cells. 2006;21(1):112–120PubMedGoogle Scholar

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© Indian Virological Society 2018

Authors and Affiliations

  1. 1.Division of Biological ProductsICAR-Indian Veterinary Research InstituteIzatnagar, BareillyIndia
  2. 2.Division of Biological StandardizationICAR-Indian Veterinary Research InstituteIzatnagar, BareillyIndia

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