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Two nonclinical studies were performed to evaluate the biodistribution, local tolerance and potential local and systemic toxic effects of this vaccine. In the biodistribution study, rats received a single intramuscular injection of either ChAd3\u2010EBO\u2010Z or saline. Enlargement of the draining lymph nodes, starting on day 2, was noticed in ChAd3\u2010EBO\u2010Z\u2010treated rats, indicating that an immune response had taken place. Viral DNA was mainly found at the injection sites and in the draining lymph nodes, from where it progressively disappeared during the observation period, while it was found only transiently and occasionally in other organs. In the repeated\u2010dose toxicity study, either ChAd3\u2010EBO\u2010Z or saline was administered intramuscularly to rabbits on two occasions with a 2\u2010week interval. General health status, rectal temperature, local tolerance, ophthalmology, hematology, coagulation and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed. Treatment\u2010related changes included a transient increase in neutrophil count, C\u2010reactive protein and fibrinogen levels, and a transient decrease in platelet count. As expected, microscopic observations 3 days after the second injection were related to the elicited inflammatory reaction, and these inflammatory responses had almost completely disappeared 29 days after the second immunization. In conclusion, the vaccine was locally and systemically well\u2010tolerated and the viral vector was partially or totally cleared from the organs where it disseminated, supporting the clinical development of the vaccine.<\/jats:p>","DOI":"10.1002\/jat.3941","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:15:56Z","timestamp":1579652156000},"page":"748-762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nonclinical safety assessment of repeated administration and biodistribution of ChAd3\u2010EBO\u2010Z Ebola candidate vaccine"],"prefix":"10.1002","volume":"40","author":[{"given":"Camille","family":"Planty","sequence":"first","affiliation":[{"name":"GSK, Rixensart  Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Chevalier","sequence":"additional","affiliation":[{"name":"Citoxlab  \u00c9vreux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010\u00c8ve","family":"Duclos","sequence":"additional","affiliation":[{"name":"Citoxlab  \u00c9vreux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1874-2876","authenticated-orcid":false,"given":"Cl\u00e9mentine","family":"Chalmey","sequence":"additional","affiliation":[{"name":"Citoxlab  \u00c9vreux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9473-6761","authenticated-orcid":false,"given":"Catherine","family":"Thirion\u2010Delalande","sequence":"additional","affiliation":[{"name":"Citoxlab  \u00c9vreux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9cile","family":"Sobry","sequence":"additional","affiliation":[{"name":"Citoxlab  \u00c9vreux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-6164","authenticated-orcid":false,"given":"Ann\u2010Muriel","family":"Steff","sequence":"additional","affiliation":[{"name":"GSK  Rockville Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8701-0372","authenticated-orcid":false,"given":"Eric","family":"Destexhe","sequence":"additional","affiliation":[{"name":"GSK, Rixensart  Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00649"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3314"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/71.4.470"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-2254(199909\/10)1:5<360::AID-JGM54>3.0.CO;2-Q"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0297"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00486-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2013.04.003"},{"key":"e_1_2_9_9_1","unstructured":"EMA\u2010CPMP. 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