ABSTRACT
The emergence of rapidly spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a major challenge to the ability of vaccines and therapeutic antibodies to provide immunity. These variants contain mutations at specific amino acids that might impede vaccine efficacy. BriLife(R) (rVSV-{Delta}G-spike) is a newly developed SARS-CoV-2 vaccine candidate currently in Phase II clinical trials. It is based on a replication competent vesicular stomatitis virus (VSV) platform. rVSV-{Delta}G-spike contains several spontaneously-acquired spike mutations that correspond to SARS-CoV-2 variants mutations. We show that human sera from BriLife(R) vaccinees preserve comparable neutralization titers towards alpha, gamma and delta variants, and show less than 3-fold reduction in neutralization capacity of beta and omicron compared to the original virus. Taken together, we show that human sera from BriLife(R) vaccinees overall maintain neutralizing antibody response against all tested variants. We suggest that BriLife(R) acquired mutations may prove advantageous against future SARS-CoV-2 VOCs.
ABSTRACT
rVSV-{Delta}G-SARS-CoV-2-S is a clinical stage (Phase 2) replication competent recombinant vaccine against SARS-CoV-2. Nonclinical safety, immunogenicity and efficacy studies were conducted in 4 animal species, using multiple dose levels (up to 108 PFU/animal) and various dosing regimens. There were no treatment related mortalities in any study, or any noticeable clinical signs. Compared to unvaccinated controls, hematology and biochemistry parameters were unremarkable and no adverse histopathological findings gave cause for safety concern in any of the studies. There was no viral shedding in urine, nor viral RNA detected in whole blood or serum samples 7 days post vaccination. The rVSV-{Delta}G-SARS-CoV-2-S vaccine immune response gave rise to neutralizing antibodies, cellular immune response, and increased lymphocytic cellularity in the spleen germinal centers and regional lymph node. No evidence for neurovirulence was found in C57BL/6 immune competent mice or in highly sensitive IFNAR KO mice. Vaccine virus replication and distribution in K18 hACE2 transgenic mice showed a gradual clearance from the vaccination site with no vaccine virus recovered from the lungs. The rVSV-{Delta}G-SARS-CoV-2-S vaccine was well tolerated locally and systemically and elicited an effective immunogenic response up to the highest dose tested, supporting further clinical development.