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Thesis Issued 2026-09-03 EN

Development of Cell Culture Based Peste Des Petits Ruminants Virus Vaccine Candidate from Local Isolates

Author: Md. Saiful Islam Siddiqui

Abstract

Peste des Petits Ruminants (PPR) is an acute highly contagious viral disease of small ruminants. The disease is endemic in Bangladesh since 1993 and causes huge economic losses due to its high morbidity and mortality. Although a vaccine is currently being used in the country to control PPR but its efficacy is questionable; outbreaks of PPR are noticed frequently despite vaccination. Moreover the vaccine virus currently being used in Bangladesh is almost 20 years old; isolation history of this strain is not known and genetic analyses of the vaccine virus revealed remarkable variations with field strains. To address this problem a vaccine based on local isolate with known biological and genetic properties is required. Therefore, the present study was undertaken to develop a vaccine candidate from the local isolates. PPR virus was isolated from natural PPR outbreaks of goats, confirmed by RT-PCR and used as viral inoculum for serial passaging in Vero cells for adaptation and attenuation. A total of 60 serial passages were completed and RT-PCR and real time RT-PCR were done at every 5 passages for confirmation of the presence of PPR virus in tissue culture fluid (TCF). To assess the adaptation and attenuation of the virus at 60th passage level, cytopathology, virus titration and sequencing of F gene were done. To determine the optimum time point for harvesting of infectred Vero cells for maximum yield of attenuated virus, growth kinetics of the attenuated virus was studied. Live animal experimentation was performed to deterimine the immunogenicity and protective efficacy of the attenuated virus. Cytopathology produced by PPR virus in infected Vero cells included syncytia formation, development of both intranuclear and intracytoplasmic inclusion body and finally cell degradation. As the number of passage progressed, syncytia development was rapid, both the number and size of the syncytia increased. At 60th passage level, the first syncytia appeared at 24 hour post inoculation (hpi) with the fusion of 3 cells together, with gradual increase of the number of cells in the syncytia up to 15 cells at 60 hpi. The titre of PPRV also increased with the number of passages from 2.5 to 6.5 Log10 TCID50/ml. On growth curve assay, the peak virus titre was observed at 72 hpi at 60th passage. Partial F gene sequence revealed 14 nucleotides and 4 amino acids substitution of PPRV at 60th passage. Both fresh and lyophilized TCF of 60th passage were found immunogenic (average CP value 15.73) and 100%protective against PPRV challenge in live goats. The 60th serially passaged PPR virus can be used as a potent PPR vaccine candidate.