Population- and Variant-Based Genome Analyses of Viruses from Vaccine-Derived Rabies Cases Demonstrate Product Specific Clusters and Unique Patterns

Calvelage, Sten; Smreczak, Marcin; Orłowska, Anna; Freuling, Conrad Martin; Müller, Thomas; Fehlner-Gardiner, Christine; Nadin-Davis, Susan A.; Höper, Dirk W.; Trębas, Paweł

doi:10.3390/v12010115

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…Apart from a G/A ambiguity at base 25, introduced due to degeneracy of the amplification primer, only one other non-conserved base was identified in one sample, QC.2015.0068RFX, for which base 6663 was identified either as a T or as ambiguous T/C. These results confirm the high level of accuracy of this sequencing approach as recently reported elsewhere [ 56 ].…”

Section: Resultssupporting

confidence: 88%

Relationships between fox populations and rabies virus spread in northern Canada

et al. 2021

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Rabies spreads in both Arctic (Vulpes lagopus) and red foxes (Vulpes vulpes) throughout the Canadian Arctic but limited wildlife disease surveillance, due to the extensive landmass of the Canadian north and its small widely scattered human population, undermines our knowledge of disease transmission patterns. This study has explored genetic population structure in both the rabies virus and its fox hosts to better understand factors that impact rabies spread. Phylogenetic analysis of 278 samples of the Arctic lineage of rabies virus recovered over 40 years identified four sub-lineages, A1 to A4. The A1 lineage has been restricted to southern regions of the Canadian province of Ontario. The A2 lineage, which predominates in Siberia, has also spread to northern Alaska while the A4 lineage was recovered from southern Alaska only. The A3 sub-lineage, which was also found in northern Alaska, has been responsible for virtually all cases across northern Canada and Greenland, where it further differentiated into 18 groups which have systematically evolved from a common predecessor since 1975. In areas of Arctic and red fox sympatry, viral groups appear to circulate in both hosts, but both mitochondrial DNA control region sequences and 9-locus microsatellite genotypes revealed contrasting phylogeographic patterns for the two fox species. Among 157 Arctic foxes, 33 mitochondrial control region haplotypes were identified but little genetic structure differentiating localities was detected. Among 162 red foxes, 18 control region haplotypes delineated three groups which discriminated among the Churchill region of Manitoba, northern Quebec and Labrador populations, and the coastal Labrador locality of Cartwright. Microsatellite analyses demonstrated some genetic heterogeneity among sampling localities of Arctic foxes but no obvious pattern, while two or three clusters of red foxes suggested some admixture between the Churchill and Quebec-Labrador regions but uniqueness of the Cartwright group. The limited population structure of Arctic foxes is consistent with the rapid spread of rabies virus subtypes throughout the north, while red fox population substructure suggests that disease spread in this host moves most readily down certain independent corridors such as the northeastern coast of Canada and the central interior. Interestingly the evidence suggests that these red fox populations have limited capacity to maintain the virus over the long term, but they may contribute to viral persistence in areas of red and Arctic fox sympatry.

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Section: Resultssupporting

confidence: 88%

Relationships between fox populations and rabies virus spread in northern Canada

et al. 2021

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“…Subsequently, a vaccination corridor in this area was established and baits have been distributed annually to prevent spread of rabies ever since. Although highly efficacious, SAD B19 and other 1st generation vaccines are associated with certain safety issues such as residual pathogenicity and vaccine associated rabies cases have been reported from several countries in different animal species using this type of vaccine [6][7][8][9][10]. Hence, upon the development of more attenuated vaccines, vaccine baits containing 2nd and more recently a 3rd generation oral rabies vaccine virus were distributed in Finland.…”

Section: Introductionmentioning

confidence: 99%

Oral vaccination of foxes and raccoon dogs against rabies with the 3rd generation oral rabies virus vaccine, SPBN GASGAS, in Finland

Vos¹,

Nokireki

Isomursu

et al. 2021

Acta Vet Scand

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Background To prevent re-emergence of wildlife-mediated rabies in Finland, oral rabies vaccine baits are distributed every year during autumn in southern Finland in a vaccination zone bordering Russia. Recently, Finland introduced a 3rd generation oral rabies virus vaccine bait. By analysing bait uptake and seroconversion in red foxes and raccoon dogs, the field efficacy of this new vaccine strain, SPBN GASGAS, was compared with the originally used highly efficacious 1st generation vaccine SAD B19. Results Overall, 74.6% and 53.9% of the animals submitted from the vaccination area after the campaigns (2017–2019) tested positive for the presence of the bait marker and anti-rabiesvirus antibodies, respectively. No significant difference was observed between years, species and vaccine. Conclusions The field performance of the highly attenuated 3rd generation oral rabies vaccine, SPBN GASGAS, in terms of bait uptake and seroconversion was similar to the 1st generation vaccine, SAD B19, and therefore offers a suitable alternative.

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“…While it was initially assumed that there was a change in the vaccine strain used in Lysvulpen in the past ( 4 ), it was later verified that some of the SAD-derived vaccines comprise virus populations rather than a single homogeneous variant ( 3 , 15 ), making it impossible to distinguish between SAD Bern and SAD B19. Partial sequence analysis using the PCR fragment already indicated the presence of a SAD-based vaccine virus strain, i.e .…”

Section: Discussionmentioning

confidence: 99%

Vaccine-induced rabies in a red fox in Poland

Smreczak

Orłowska

Müller

et al. 2022

Journal of Veterinary Research

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Introduction Rabies as a zoonosis threatens public health worldwide. Several thousand people die each year of infections by the rabies virus (RABV). Oral rabies vaccination (ORV) of wildlife was successfully implemented in many European countries and led to rabies being brought under control there. In Poland, ORV was introduced in 1993 using vaccines containing an attenuated strain of the rabies virus. However, attenuated rabies viruses may have residual pathogenicity and cause the disease in target and non-target animals. Material and Methods A red fox carcass was tested as part of national rabies surveillance, and its brain was screened for RABV infection using two conjugates and a fluorescent antibody test (FAT). The rabies virus was isolated in mouse neuroblastoma cells by rabies tissue culture infection test (RTCIT), and viral RNA was detected by heminested reverse transcriptase PCR (hnRT-PCR) as well as by quantitative real-time RT-PCR (rtRT-qPCR). An amplicon of 600 bp was subjected to Sanger sequencing. To differentiate between vaccine and field RABV strains, PCR-restriction fragment length polymorphism (PCR-RFLP) using the Dra I, Msp I, Nla IV and Mbo II restriction endonucleases was performed. Results The rabies virus was detected in the fox’s brain using FAT, RTCIT and molecular tests. The PCR-RFLP revealed of vaccine-induced rabies, and full-length genome analysis showed 100% nucleotide sequence identity of the isolate with the reference sequences of Street Alabama Dufferin Bern (SAD Bern) vaccine strains and other vaccine-induced rabies virus isolates detected in animals and deposited in GenBank. Conclusion We detected vaccine-induced rabies for the first time in Poland in a fox during routine rabies surveillance.

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Population- and Variant-Based Genome Analyses of Viruses from Vaccine-Derived Rabies Cases Demonstrate Product Specific Clusters and Unique Patterns

Cited by 10 publications

References 34 publications

Relationships between fox populations and rabies virus spread in northern Canada

Relationships between fox populations and rabies virus spread in northern Canada

Oral vaccination of foxes and raccoon dogs against rabies with the 3rd generation oral rabies virus vaccine, SPBN GASGAS, in Finland

Vaccine-induced rabies in a red fox in Poland

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