Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets.

Michael J Kuiper,Julian D Druce,Seshadri S Vasan,Sarah Goldie,Shane Riddell,Trevor R F Smith,Mary Tachedjian,Peter A Durr,Kate E Broderick,Alexander J Mcauley,Kim R Blasdell

doi:10.3389/fimmu.2021.694857

Abstract

The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These “variants-of-concern” have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative ‘G614’, ‘501Y.V1’ and ‘501Y.V2’ virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported by in silico biomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines.

Highlights

With the continuing roll-out of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily developed against the ancestral ‘D614’ version of the virus [1], there is concern that emerging ‘variants-of-concern’ and ‘variants-of-interest’ may have acquired mutations resulting in lower neutralisation by infection- and vaccine-induced antibodies
We recently investigated the neutralisation of SARS-CoV-2 isolates containing either the ‘D614’ or the ‘G614’ variation of the Spike protein, using serum samples from ferrets vaccinated with INO-4800, a leading DNA vaccine candidate under clinical evaluation against SARS-CoV-2 [9, 10], demonstrating the D614G mutation was unlikely to affect vaccine-induced antibody-mediated virus neutralisation
Stocks of VIC31, the G614 isolate used in our previous study [9]; VIC17990, an Australian isolate of the 501Y.V1 variant; and 501Y.V2.HV001, a South African isolate of the 501Y.V2 variant, were propagated and titrated in Vero E6 cells prior to use, with genome sequences confirmed by next-generation sequencing

Summary

Introduction

With the continuing roll-out of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily developed against the ancestral ‘D614’ version of the virus [1], there is concern that emerging ‘variants-of-concern’ and ‘variants-of-interest’ may have acquired mutations resulting in lower neutralisation by infection- and vaccine-induced antibodies. INO-4800 Neutralisation of SARS-CoV-2 Variants primates [2,3,4], so the determination of antibody-mediated neutralisation against emerging variants is important when assessing vaccine efficacy. Neutralisation studies using human serum samples from coronavirus disease-19 (COVID-19) patients in South Africa reveal significant decreases in neutralisation efficiency against the 501Y.V2 variant [6, 7]. Almost two thirds of the vaccines in development are in the pre-clinical phase, meaning that human serum samples are not available for determination of neutralisation efficacy against emerging variants. It is important that appropriate animal-derived samples demonstrate similar neutralisation responses to SARS-CoV-2 variants as human vaccinees for the determination of continued vaccine efficacy before such candidates progress into human clinical trials

Methods

Results

Conclusion