CORD-19:0beba87e3366b16efad5fc85a9fb2be33e63e019 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
T1 658-836 Epistemic_statement denotes Furthermore, the recombinant virus is capable of horizontal spreading promoting protection of contact animals, thus providing the opportunity to immunize wild rabbit populations.
T2 837-924 Epistemic_statement denotes However, potential risks must be extensively evaluated before considering its ®eld use.
T3 925-1041 Epistemic_statement denotes In this study several safety issues concerning the proposed vaccine have been evaluated under laboratory conditions.
T4 1042-1124 Epistemic_statement denotes Results indicated that vaccine administration is safe even at a 100-fold overdose.
T5 1818-1920 Epistemic_statement denotes In European rabbits however, MV causes the systemic and lethal infection known as myxomatosis [2, 3] .
T6 2682-2793 Epistemic_statement denotes The etiological agent, rabbit haemorrhagic disease virus (RHDV), is a member of the Caliciviridae family [13] .
T7 3089-3287 Epistemic_statement denotes In the last years, the VP60 gene has been successfully expressed in several heterologous systems [15±23] and has been shown to induce full protection of rabbits against a lethal challenge with RHDV.
T8 3288-3637 Epistemic_statement denotes While the currently available vaccines against myxomatosis and RHD have proven eective in the control of these diseases in domestic rabbits, they are not suited to immunize wild rabbit populations, as vaccines need to be delivered individually by conventional veterinary practices, which is not a feasible approach to vaccinate free ranging animals.
T9 3638-3834 Epistemic_statement denotes As a novel approach for wildlife vaccination, we have explored the possibility of developing``transmissible vaccines'' by the use of viral vectors capable of spreading within an animal population.
T10 4557-4770 Epistemic_statement denotes Furthermore, the recombinant 6918VP60-T2 virus showed a limited horizontal transmission capacity, either by direct contact or in a¯ea-mediated process, promoting immunization of contact uninoculated animals [25] .
T11 4771-4989 Epistemic_statement denotes The promising results obtained so far under laboratory conditions suggest the recombinant 6918VP60-T2 could be used in large-scale immunization schemes for the control of myxomatosis and RHD in wild rabbit populations.
T12 4990-5107 Epistemic_statement denotes However, before considering its environmental release, vaccine safety considerations should be extensively evaluated.
T13 5108-5324 Epistemic_statement denotes Potential risks with regard to vaccine dose (i.e., accidental administration of an overdose), age, physiological condition (i.e., pregnant does) and immune status of exposed individuals, should be taken into account.
T14 5325-5444 Epistemic_statement denotes Biological stability is another important aspect to evaluate in a recombinant virus intended for environmental release.
T15 12863-12975 Epistemic_statement denotes Results indicated that administration of 6918VP60-T2 virus to immunocompromised animals was safe (either by i.d.
T16 15547-15927 Epistemic_statement denotes The biological stability of the recombinant virus, and therefore its potential to evolve to a virulent state were evaluated by comparing the eects of rabbit infection with``Passage 0'' virus (the same virus stock used in all the experiments reported in this paper), with the eects of rabbit infection with the virus obtained after 10 serial passages in rabbits (Passage 10 virus).
T17 17446-17717 Epistemic_statement denotes After 10 serial passages in rabbits, a product of 3.3 kb (the expected size for the recombinant virus) was ampli®ed by PCR with no detection of the corresponding wildtype MV 1.0 kb product (not shown), indicating that the VP60 gene was stably integrated in the MV genome.
T18 17861-17970 Epistemic_statement denotes However, control of both diseases among wild rabbit populations remains an unsolved problem of great concern.
T19 17971-18086 Epistemic_statement denotes In this regard it should be noted that the European rabbit plays a key ecological role in Mediterranean ecosystems.
T20 18187-18309 Epistemic_statement denotes Immunization of wildlife is dicult to achieve because direct delivery of vaccines to free ranging animals is not possible.
T21 18310-18380 Epistemic_statement denotes The oral route is considered a feasible way of vaccine administration.
T22 18702-18978 Epistemic_statement denotes Hopefully, the administration of a recombinant vaccine of this characteristics to a small number of captured individuals, would eventually lead to the immunization of a fraction of animals within a given population, which is sucient to reduce the spread of the target disease.
T23 18979-19163 Epistemic_statement denotes This approach might be useful, especially when the distribution, size, and turnover rate of a population precludes capture or baiting techniques as the only means for antigen delivery.
T24 19406-19531 Epistemic_statement denotes The results obtained under laboratory conditions suggest the recombinant virus might be eective for wild rabbit immunization.
T25 19532-19742 Epistemic_statement denotes However, since the proposed use of 6918VP60-T2 involves the environmental release of a recombinant virus, considerations regarding safety issues are as important as the potential ecacy of the candidate vaccine.
T26 19743-19869 Epistemic_statement denotes It is for this reason that safety concerns have been at the core of the rational design of the proposed immunization strategy.
T27 19870-19986 Epistemic_statement denotes The biological characteristics of MV make it a good candidate as a vaccine vector in terms of safety considerations.
T28 20375-20658 Epistemic_statement denotes On the other hand, given the current widespread geographic distribution of MV, which is similar to the distribution of RHDV, the ®eld use of a recombinant MV-VP60 vaccine would normally not involve the introduction of a virus species that does not already exist in a particular area.
T29 20736-20990 Epistemic_statement denotes It was decided not to use one of the available vaccinal strains, obtained by cell culture-attenuation of virulent MV strains [5] , as this would involve the release of a new strain to the environment, which might undergo reversion to virulence in nature.
T30 21250-21529 Epistemic_statement denotes This strain exhibited adequate biological characteristics for the development of a recombinant transmissible vaccine, as it caused a non-pathogenic infection comparable to that of cell culture-attenuated vaccinal strains, yet retaining the capacity of horizontal spreading [24] .
T31 21530-21875 Epistemic_statement denotes Since preservation of the valuable biological properties of 6918 strain was of major importance in the development of the recombinant virus, the foreign gene was inserted in the intergenic site between ORFs MJ2 and MJ2a, as recombinant MVs with insertions at this site have been shown to retain overall parental biological characteristics [27] .
T32 22328-22604 Epistemic_statement denotes Considering the potential risks associated with the DNA sequence inserted, it should be noted that the VP60 gene has been cloned in a wide range of heterologous systems[15±23] and no indication of toxicity or side eects associated to the expression of VP60 have been reported.
T33 22605-22871 Epistemic_statement denotes Previous results indicated that administration of either 6918 MV or recombinant 6918VP60-T2 virus to healthy rabbits under laboratory conditions by standardised procedures is safe, as all rabbits exhibited only mild clinical symptoms and rapidly recovered [24, 25] .
T34 22872-23174 Epistemic_statement denotes In this report we have extended the safety assessment of the vaccine by analysing the potential Table 5 Eects Concerning vaccine dosage and the possibility of accidental administration of an overdose, the results demonstrated vaccine safety even when a 100-fold overdose (10 6 PFU) was inoculated (Fig.
T35 24700-24939 Epistemic_statement denotes The environmental release of recombinant 6918VP60-T2 virus would involve a certain number of serial passages in its natural host, even when this capability seemed to be limited to only two serial passages under laboratory conditions [25] .
T36 24940-25062 Epistemic_statement denotes Should there be a tendency for the virus to evolve to a virulent state, serial passage in rabbits would cause it to do so.
T37 25340-25410 Epistemic_statement denotes Thus, the attenuated nature of 6918VP60-T2 seems to be a stable trait.