Publication date: Dec 20, 2025
Neutralising antibodies are a candidate correlate of protection against SARS-CoV-2, typically they are measured using live virus neutralisation assays, however, these involve high containment work, are technically demanding and can have a long turn-around time. Therefore, surrogate assays are needed to support rapid screening and vaccine trials. Here, we assessed the Meso Scale Discovery (MSD) ACE2 inhibition assay (ACE2i) as a surrogate by comparing it with live virus neutralisation and total anti-spike IgG across ancestral, Delta, and Omicron SARS-CoV-2 spike proteins. Serum from 103 immunocompromised participants in the UK OCTAVE-DUO trial were analysed at baseline and 21 days post-booster. All assays detected significant post-vaccination increases, but micro-neutralisation assay (MNA) and ACE2i showed marked reductions against VoC, particularly Omicron and this was in contrast to IgG assays. The ACE2i assay offers a rapid, scalable, low containment surrogate for neutralisation to support the licensure of new SARS-CoV-2 vaccines and variant monitoring.
Open Access PDF
| Concepts | Keywords |
|---|---|
| 21days | ACE2 competition ELISA |
| Ace2i | COVID-19 |
| Live | Immunobridging |
| Rapid | Neutralising antibodies |
| Vaccines | SARS-CoV-2 |
| Vaccine efficacy | |
| Variants of concern |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | MSD |
| disease | MESH | NHS |
| disease | MESH | COVID 19 |
| drug | DRUGBANK | Gold |
| disease | MESH | measles |
| pathway | KEGG | Measles |
| disease | MESH | infection |
| drug | DRUGBANK | Coenzyme M |
| drug | DRUGBANK | Immune Globulin Human |
| disease | MESH | strain |
| disease | MESH | Lam |
| drug | DRUGBANK | (S)-Des-Me-Ampa |
| disease | MESH | included |