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. |