Preliminary nonclinical safety and immunogenicity of an rVSV-ΔG-SARS-CoV-2-S vaccine in mice, hamsters, rabbits and pigs

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 NyskaShmuel Yitzhaki, Adi Beth-Din, Haim Levy, Nir Paran, Tomer Israely, Hadar Marcus

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)859-875
Number of pages17
JournalArchives of Toxicology
Volume96
Issue number3
DOIs
StatePublished - Mar 2022
Externally publishedYes

Keywords

  • COVID-19
  • Neutralizing antibodies
  • Nonclinical
  • Safety
  • Vaccine

Fingerprint

Dive into the research topics of 'Preliminary nonclinical safety and immunogenicity of an rVSV-ΔG-SARS-CoV-2-S vaccine in mice, hamsters, rabbits and pigs'. Together they form a unique fingerprint.

Cite this