Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy

被引:18
作者
Buijs, P. R. A. [1 ]
van Amerongen, G. [2 ]
van Nieuwkoop, S. [3 ]
Bestebroer, T. M. [3 ]
van Run, P. R. W. A. [3 ]
Kuiken, T. [3 ]
Fouchier, R. A. M. [3 ]
van Eijck, C. H. J. [1 ]
van den Hoogen, B. G. [3 ]
机构
[1] Erasmus MC, Dept Surg, Rotterdam, Netherlands
[2] Viroclin Biosci BV, Rotterdam, Netherlands
[3] Erasmus MC, Dept Virosci, NL-3015 CE Rotterdam, Netherlands
关键词
RESPIRATORY-TRACT; INFLUENZA-VIRUS; VECTORED VACCINE; FUSION PROTEIN; IMMUNIZATION; ANTIBODIES; PV701; CONJUNCTIVITIS; INFECTION; MTH-68/H;
D O I
10.1038/cgt.2014.51
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Newcastle disease virus (NDV) is an avian pararnyxovirus with oncolytic potential. Detailed preclinical information regarding the safety of Oncolytic NDV is scarce. In this study, we evaluated the toxicity, biodistribution and shedding of intravenously injected oncolytic NDVs in non-human primates (Macaca fascicularis). Two animals were injected with escalating doses of a non-recombinant Vaccine strain, a recombinant lentogenic strain or a recombinant mesogenic strain. To study transmission, naive animals: were co-housed with the injected animals. Injection with NDV did not lead to severe illness in the animals or abnormalities in hematologic or biochemistry Measurements. Injected animals shed low amounts of virus, but this did not lead to seroconversion of the contact animals. Postmortem evaluation demonstrated no pathological changes or evidence of virus replication. This study demonstrates that NDV generated in embryonated chicken eggs is safe for intravenous administration to non-human primates. In addition, our study Confirmed results from a previous report that naive primate and human sera are able to neutralize egg-generated NDV. We discuss the implications of these results for our study and the Use of NDV for virotherapy.
引用
收藏
页码:463 / 471
页数:9
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