The objectives were to evaluate the biodistribution of ChAd3вЂђEBOвЂђZ after a single intramuscular (IM) injection in rats, and the local tolerance, potential local and/or systemic toxic effects, and persistence, delayed onset or reversibility of any effects in rabbits after two IM injections. This article reports two studies performed in rats and rabbits under Good Laboratory Practice (GLP) principles. To support the development of the ChAd3вЂђEBOвЂђZ vaccine, a number of nonclinical toxicity studies were performed. It showed encouraging nonclinical efficacy, inducing protection against acute lethal EV challenge in nonhuman primates (Stanley et al., 2014).

In this context, an investigational vaccine for EVD prevention, ChAd3вЂђEBOвЂђZ, composed of the replicationвЂђdefective chimpanzee adenovirus 3 vector (ChAd3) with a DNA fragment encoding the Ebola Zaire glycoprotein (GP) was developed. This epidemic, caused by the Zaire species (one of the six known Ebolavirus species), resulted in more than 11 000 deaths (WHO, 2016), which prompted different groups to react quickly and accelerate Ebola vaccine development (Lambe, Bowyer, & Ewer, 2017). Starting in late 2013 up to 2016, the world's largest EVD outbreak was recorded in West Africa (Coltart, Lindsey, Ghinai, Johnson, & Heymann, 2017). This results in coagulation disorders and the destruction of several organs, including the liver and kidneys (Feldmann & Geisbert, 2011). EV directly causes tissue damage, either by direct cytopathic effects or through indirect effects related to the release of inflammatory mediators or alteration of vascular functions. EVD is characterized by a sudden onset of fever and weakness, accompanied by other symptoms such as headache, muscle pain, conjunctivitis, rash, and diarrhea and vomiting, with a proportion of individuals presenting hemorrhagic symptoms. In conclusion, the vaccine was locally and systemically wellвЂђtolerated and the viral vector was partially or totally cleared from the organs where it disseminated, supporting the clinical development of the vaccine.Д®bola virus disease (EVD), or Ebola hemorrhagic fever, is caused by the Ebola virus (EV) of the Filoviridae family. 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. TreatmentвЂђrelated changes included a transient increase in neutrophil count, CвЂђreactive protein and fibrinogen levels, and a transient decrease in platelet count. Macroscopic and microscopic evaluations were performed. General health status, rectal temperature, local tolerance, ophthalmology, hematology, coagulation and blood chemistry parameters were monitored. In the repeatedвЂђdose toxicity study, either ChAd3вЂђEBOвЂђZ or saline was administered intramuscularly to rabbits on two occasions with a 2вЂђweek interval. 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. Enlargement of the draining lymph nodes, starting on day 2, was noticed in ChAd3вЂђEBOвЂђZвЂђtreated rats, indicating that an immune response had taken place.

In the biodistribution study, rats received a single intramuscular injection of either ChAd3вЂђEBOвЂђZ or saline. Two nonclinical studies were performed to evaluate the biodistribution, local tolerance and potential local and systemic toxic effects of this vaccine.

ChAd3вЂђEBOвЂђZ is an investigational adenovirusвЂђbased vaccine for the prevention of Ebola virus disease.

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