Evidence map›Paper›PMID 40102474›Full record

ArticleNature communications2025

Complement-mediated enhancement of SARS-CoV-2 antibody neutralisation potency in vaccinated individuals.

Jack Mellors, Raman Dhaliwal, Stephanie Longet, Tom Tipton, OCTAVE Consortium, OPTIC Consortium, Eleanor Barnes, Susanna J Dunachie, Paul Klenerman, Julian Hiscox and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Jack MellorsCentre for Human Genetics and the Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. jmellors@ic.ac.uk.ORCID http://orcid.org/0000-0001-7761-8341
Raman DhaliwalSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Stephanie LongetCentre International de Recherche en Infectiologie, Université Jean Monnet, Université Claude Bernard Lyon, Inserm, Saint-Etienne, France.
Tom TiptonCentre for Human Genetics and the Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
OCTAVE Consortium
OPTIC Consortium
Eleanor BarnesNIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Susanna J DunachieNIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Paul KlenermanNIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Julian HiscoxDepartment of Infection Biology and Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Miles CarrollCentre for Human Genetics and the Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. miles.carroll@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0002-7026-7187

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

With the continued emergence of SARS-CoV-2 variants and concerns of waning immunity, there is a need for better defined correlates of protection to aid future vaccine and therapeutic developments. Whilst neutralising antibody titres are associated with protection, these are typically determined in the absence of the complement system, which has the potential to enhance neutralisation titres and strengthen correlates with protection in vivo. Here we show that replenishment of the complement system in neutralisation assays can significantly enhance neutralisation titres, with up to an ~83-fold increase in neutralisation of the BA.1.1.529 strain using cross-reactive sera from vaccination against the ancestral strain. The magnitude of enhancement significantly varies between individuals, viral strains (wild-type/VIC01 and Omicron/BA.1), and cell lines (Vero E6 and Calu-3), and is abrogated following heat-inactivation of the complement source. Utilising ACE2 competition assays, we show that the mechanism of action is partially mediated by reducing ACE2-spike interactions. Through the addition of compstatin (a C3 inhibitor) to live virus neutralisation assays, the complement protein C3 is shown to be required for maximum efficiency. These findings further our understanding of SARS-CoV-2 immunity and neutralisation, with implications for protection against emerging variants and assessing future vaccine and therapeutic developments.

Indexed as

Antibodies, NeutralizingAntibodies, ViralComplement System ProteinsCOVID-19COVID-19 VaccinesSARS-CoV-2Angiotensin-Converting Enzyme 2AnimalsChlorocebus aethiopsCross ReactionsFemaleHumansNeutralization TestsPeptides, CyclicSpike Glycoprotein, CoronavirusVaccinationACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralComplement System ProteinscompstatinCOVID-19 VaccinesPeptides, CyclicSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID40102474
PMCPMC11920438

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.