rVSV-ΔG-SARS-CoV-2-S vaccine: repeated intramuscular (IM) toxicity, local tolerance, immunogenicity and biodistribution study in NZW rabbits.

Abstract

BriLife®, a vector-based vaccine that utilizes the recombinant vesicular stomatitis virus (VSV) platform to express and present the spike antigen of SARS-CoV-2, is undergoing testing in a phase 2 clinical trial in Israel. A nonclinical repeated-dose (GLP) toxicity study in New Zealand white rabbits was performed to evaluate the potential toxicity, local tolerance, immunogenicity and biodistribution of the vaccine. rVSV-ΔG-SARS-CoV-2-S (or vehicle) was administered intramuscularly to two groups of animals (106, 107 PFU/animal, n = 10/sex/group) on three occasions, at 2-week intervals, followed by a 3-week recovery period. Systemic clinical signs, local reactions, body weight, body temperature, food consumption, ophthalmology, urinalysis, clinical pathology, C-reactive protein, viremia and antibody levels were monitored. Gross pathology was performed, followed by organs/tissues collection for biodistribution and histopathological evaluation. Treatment-related changes were restricted to multifocal minimal myofiber necrosis at the injection sites, and increased lymphocytic cellularity in the iliac and mesenteric lymph nodes and in the spleen. These changes were considered related to the inflammatory reaction elicited, and correlated with a trend for recovery. Detection of rVSV-ΔG-SARS-CoV-2-S vaccine RNA was noted in the regional iliac lymph node in animals assigned to the high-dose group, at both termination time points. A significant increase in binding and neutralizing antibody titers was observed following vaccination at both vaccine doses. In view of the findings, it was concluded that the rVSV-ΔG-SARS-CoV-2-S vaccine is safe. These results supported the initiation of clinical trials.

• Authors: Amir Rosner, Michal Steiner, Sharon Melamed, Boaz Politi, Einat Vitner, Hadas Tamir, Hagit Achdout, Lilach Cherry, Roy Avraham, Yfat Yahalom-Ronen, Haim Levy, Adi Beth-Din, Dana Stein, Adva Mechaly, Morly Fisher, Ella Fatelevich, Shay Weiss, Noam Kronfeld, Liora Madar-Shapiro, Abraham Nyska, Shmuel Yitzhaki, Nir Paran, Tomer Israely, Hadar Marcus, Noa Madar-Balakirski
• Journal: Archives of toxicology (Arch Toxicol) Vol. 96 Issue 8 Pg. 2329-2339 (08 2022) ISSN: 1432-0738 [Electronic] Germany
• PMID: 35577986 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines

Topics

• Animals
• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 (prevention & control)
• COVID-19 Vaccines (adverse effects)
• Rabbits
• SARS-CoV-2
• Tissue Distribution