Preliminary nonclinical safety and immunogenicity of an rVSV-ΔG-SARS-CoV-2-S vaccine in mice, hamsters, rabbits and pigs
| Autor: | Noa Madar-Balakirski, Amir Rosner, Sharon Melamed, Boaz Politi, Michal Steiner, Hadas Tamir, Yfat Yahalom-Ronen, Elad Bar-David, Amir Ben-Shmuel, Assa Sittner, Itai Glinert, Shay Weiss, Erez Bar-Haim, Hila Cohen, Uri Elia, Hagit Achdout, Noam Erez, Shahar Rotem, Shlomi Lazar, Abraham Nyska, Shmuel Yitzhaki, Adi Beth-Din, Haim Levy, Nir Paran, Tomer Israely, Hadar Marcus |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Vaccines
Synthetic COVID-19 Vaccines Membrane Glycoproteins Mesocricetus Swine Health Toxicology and Mutagenesis Vaccination COVID-19 General Medicine Toxicology Neutralizing antibodies Antibodies Viral Antibodies Neutralizing Mice Inbred C57BL Nonclinical Mice Viral Envelope Proteins Immunotoxicology Cricetinae Animals Female Rabbits Safety Vaccine |
| Zdroj: | Archives of Toxicology |
| ISSN: | 1432-0738 0340-5761 |
| Popis: | rVSV-ΔG-SARS-CoV-2-S is a clinical stage (Phase 2) replication competent recombinant vaccine against SARS-CoV-2. To evaluate the safety profile of the vaccine, a series of non-clinical safety, immunogenicity and efficacy studies were conducted in four animal species, using multiple doses (up to 108 Plaque Forming Units/animal) and dosing regimens. There were no treatment-related mortalities or any noticeable clinical signs in any of the studies. Compared to unvaccinated controls, hematology and biochemistry parameters were unremarkable and no adverse histopathological findings. There was no detectable viral shedding in urine, nor viral RNA detected in whole blood or serum samples seven days post vaccination. The rVSV-ΔG-SARS-CoV-2-S vaccination gave rise to neutralizing antibodies, cellular immune responses, and increased lymphocytic cellularity in the spleen germinal centers and regional lymph nodes. No evidence for neurovirulence was found in C57BL/6 immune competent mice or in highly sensitive type I interferon knock-out mice. Vaccine virus replication and distribution in K18-human Angiotensin-converting enzyme 2-transgenic mice showed a gradual clearance from the vaccination site with no vaccine virus recovered from the lungs. The nonclinical data suggest that the rVSV-ΔG-SARS-CoV-2-S vaccine is safe and immunogenic. These results supported the initiation of clinical trials, currently in Phase 2. Supplementary Information The online version contains supplementary material available at 10.1007/s00204-021-03214-w. |
| Databáze: | OpenAIRE |
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