Neutralization of SARS-CoV-2 Variants by rVSV-ΔG-Spike-Elicited Human Sera

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 of specific amino acids that might impede vaccine efficacy. BriLife® (rVSV-ΔG-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. The rVSV-ΔG-spike contains several spontaneously acquired spike mutations that correspond to SARS-CoV-2 variants’ mutations. We show that human sera from BriLife® vaccinees preserve comparable neutralization titers towards alpha, gamma, and delta variants and show less than a three-fold reduction in the neutralization capacity of beta and omicron compared to the original virus. Taken together, we show that human sera from BriLife® vaccinees overall maintain a neutralizing antibody response against all tested variants. We suggest that BriLife®-acquired mutations may prove advantageous against future SARS-CoV-2 VOCs.

SARS-CoV-2 3CL pro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376

“…Recently, chimeric VSV variants with SARS-CoV-2 spike were used to predict spike protein immune escape mutations by selecting against neutralizing serum ( 39 – 41 ). The fast occurrence of mutations was facilitated in those studies by the high error rate of the VSV polymerase ( 20 , 21 ).…”

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

“…It is noteworthy that during the development and manufacturing processes, rVSV-ΔG-SARS-CoV-2-S vaccine acquired spontaneous mutations at sites of major importance to antibody-mediated immunity, some of which are identical, or correspond to some of the key mutations or areas of SARS-CoV-2 variants of concern (VOCs), namely N501, E484, Q493 and G685. The ability of rVSV-ΔG-SARS-CoV-2-S to maintain neutralizing antibody response against alpha, gamma and delta variants was recently demonstrated in human sera (Yahalom-Ronen et al 2022 ). This may provide an advantage of rVSV-ΔG-SARS-CoV-2-S vaccine against future SARS-CoV-2 VOCs and illustrates the potential value of employing a vector-based vaccination platform.…”

A Novel Quantitative Multi-Component Serological Assay for SARS-CoV-2 Vaccine Evaluation

“…The performance of the array was verified with the WHO first international standard (IS), a reference serum (comprised of 11 convalescent individuals) that was introduced by the WHO Expert Committee on Biological Standardization in December 2020 with the aim of harmonizing immune response assessment after natural infection or vaccination. , The serum was assigned an arbitrary value of 1000 units/mL for binding/neutralizing assays and can thus be used to assist in standardizing our results, compared to other assays detecting the same class of immunoglobulins with the same specificity. We recently assessed the neutralization capacity of a small subset of the vaccinated volunteers’ sera against SARS-CoV-2 and several of its relevant circulating variants-of-concern, demonstrating the high potency of BriLife against the tested viruses . Moving forward, the binding data collected from the serological array, in combination with the neutralization data, may allow the generation of a binding/neutralizing correlate of protection for BriLife as was demonstrated for the mRNA-1273 vaccine …”

“…We recently assessed the neutralization capacity of a small subset of the vaccinated volunteers' sera against SARS-CoV-2 and several of its relevant circulating variants-of-concern, demonstrating the high potency of BriLife against the tested viruses. 15 Moving forward, the binding data collected from the serological array, in combination with the neutralization data, may allow the generation of a binding/neutralizing correlate of protection for BriLife as was demonstrated for the mRNA-1273 vaccine. 16 As indicated, this multi-component array was developed to evaluate the immunogenicity of BriLife, the Israeli vaccine (results will be published elsewhere, at the end of phase I/II of the clinical trial).…”