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The purpose of this review is to carry out an overall evaluation of the scientific literature on the selection of the best candidate as an animal translation model. We used the PubMed/MEDLINE, Web of Science Core Collection and medRxiv/BioRxiv (preprint materials) databases for original research published in English to September 2020. Review research was conducted in accordance with the preferred reporting elements for systematic reviews and meta-analysis (PRISMA). The inclusion criteria were: establishing animal models (mouse, ferret, dog, cat, primates, etc.) for SARSCoV-2, prophylaxis, therapy and vaccines. The exclusion criteria were: books, guidelines and protocols, population genetics. This review highlights the distinct advantages and limitations of each animal model, which should be taken into account in the design of studies, the interpretation of pathogenic mechanisms or extrapolation of the results of therapy or vaccines in humans. In order to generate results that are consistent, reproducible and comparable between studies, it is necessary to harmonize the protocols for experimentation on animal models. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection increases the risk of multi-organ systemic complications and venous and arterial thromboembolism. The development of vaccines has proven to be an effective method to combat severe forms of infection. Adverse effects reported after COVID-19 vaccination consisted of local injection site reaction, fatigue, myalgia, or fever as well as sporadic cases of vaccine-induced thrombotic immune thrombocytopenia, especially viral vector vaccines. Objectives: The aim of the study was to evaluate the repeated dose toxicity of a candidate vaccine against SARS- CoV-2, a test in which several parameters were analyzed, including coagulation factors. Materials and methods: The test included 120 rats, of both sexes, divided into six groups (main group, recovery group and control group) at which the human dose, 10X human dose and 1 control adjuvant were tested. The vaccine was administered intranasally, 4 times every two weeks. The final day was after the last administration to the main group and another 30 days from the last administration to the recovery group. On day 0 and the final day, blood was collected for hematological, biochemical, immunological examinations and coagulation tests (Fibrinogen, Prothrombin Time-PT, Activated Partial Thromboplastin Time-aPTT and Thrombin Time-TT). Results: Fibrinogen, in the case of all groups, increased on the final day, except for females from the recovery groups where this parameter decreased by 25%. PT, aPTT and TT, regardless of group or sex, had low values compared to the initial time of the study. On day 0, the values of the coagulation factors were homogeneous, the fibrinogen being between 155- 347mg / dL, PT 25.5-57.8 sec, aPTT 61.9-120 sec and TT values of 53-60 sec. On the final day, the group analysis also showed unit values. Fibrinogen increased between 90-116%, PT decreased by 48-71%, aPTT decreased by 59-80%, and TT had values lower by 10-14% compared to the initial day. Conclusions: Increased fibrinogen associated with decreased PT and aPTT is common in human clinical pathology. Fibrinogen, PT, aPTT and TT are the standard parameters of blood clotting assessed in toxicity tests. The results obtained in the study represent a preliminary phase which, corroborated with the results of the other tests, supports the conclusion that the candidate vaccine does not have toxicological potential, the coagulation factors not being influenced after its repeated administration. [ABSTRACT FROM AUTHOR]

In the context of SARS-CoV-2 infection, the identification of a vaccine has become vital for stopping the pandemic. The consortium formed by the OncoGen Center and the Cantacuzino Institute (CI) evaluates a candidate vaccine whose vaccine component is represented by a combination of peptides specifically recognized by the 2 components of the adaptative immune system. Each new vaccine must undergo mandatory tests, even if they are currently accelerated or overlapping, with the consent of the European Medicines Agency (EMA). One of the tests relates to repeated dose toxicity. The aim was to setup a protocol for repeated dose toxicity testing in rats, the results of which would allow the transition to the clinical phase I dossier. The protocol was designed based on EMA guidelines for vaccine safety testing and rat-human translation. The proposed human dose, route of administration and repeat administration were taken into account. Clinical signs, immunological and biochemical parameters will be analysed. Histological examination will be performed on 34 organs. The protocol was approved by the ethics committee of the CI and authorized by the competent authority. In order to evaluate the repeated dose toxicity of a vaccine candidate against COVID-19, we propose a robust, replicable, effective and translational study protocol. [ABSTRACT FROM AUTHOR]