---
title: "Neutralising antibodies and vaccine protection against progression to severe COVID-19: Meta-analys"
id: "plos-medicine-0-neutralising-antibodies-and-protection-from-progression-to-severe-covid-19-a"
canonical_url: "https://medichelpline.com/clinical-feed/plos-medicine-0-neutralising-antibodies-and-protection-from-progression-to-severe-covid-19-a"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PLOS Medicine"
source_url: "https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230"
published_at: "2026-09-02T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Neutralising antibodies and vaccine protection against progression to severe COVID-19: Meta-analys
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-medicine-0-neutralising-antibodies-and-protection-from-progression-to-severe-covid-19-a
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PLOS Medicine
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230)
- **Published At:** 2026-09-02T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This meta-analysis synthesized clinical and immunological data to assess whether vaccine-induced **neutralising antibodies** correlate with protection from progression to severe COVID-19 (hospital or ICU admission) after infection. - The authors systematically identified 25 published clinical studies reporting vaccine protection against progression from SARS-CoV-2 infection to severe outcomes. - They matched clinical effect estimates to neutralisation titre data compiled from 301 post-vaccination studies in the Stanford Coronavirus antiviral and resistance database. - Data were combined using meta-regression to relate geometric mean neutralisation titres (GMT) to vaccine protection from progression to severe disease. - A 10-fold increase in vaccine GMT was associated with a reduced relative risk (RR) of progression to severe COVID-19: RR 0.57 per 10-fold increase (95% CI 0.51–0.64, p < 0.001). - The analysis indicates vaccine-induced neutralising antibodies are correlated with, and can partially account for, protection from progression to severe COVID-19. - Protection from progression provided by vaccination exceeded that seen with therapeutic passive administration of antibodies given to infected unvaccinated individuals. - Main limitations include that neutralisation titres and clinical outcomes were measured in different studies (no individual-level matched measurements) and potential unmeasured confounding in the matched datasets. - The authors conclude other immune responses (for example, T cell immunity or nonneutralising antibody functions) and timing of antibody presence during breakthrough infection likely contribute to the residual protection gap between vaccination and passive antibody therapy. - Code and data supporting the study are publicly available via a Zenodo DOI as reported in the article. - The study was published in PLoS Medicine on September 2, 2026, and was funded by Australian research grants; authors declared no competing interests.
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosmedicine%2Farticle%3Fid%3D10.1371%2Fjournal.pmed.1005230) * * About * Browse * Publish * [](https://journals.plos.org/plosmedicine/ "PLOS Medicine") * Search [advanced search](https://journals.plos.org/plosmedicine/search) * 0 [Save](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#savedHeader) * 0 [Citation](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#citedHeader) * 64 [View](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#viewedHeader) * 0 [Share](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230#discussedHeader) Open Access Peer-reviewed Research Article # Neutralising antibodies and protection from progression to severe COVID-19: A meta-analysis * Karen M. Elias, Roles Conceptualization, Data curation, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review & editing Affiliation Kirby Institute, University of New South Wales, Sydney, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0009-0000-4989-5552 ](https://orcid.org/0009-0000-4989-5552 "ORCID Registry") ⨯ * Ainslie Mitchell, Roles Data curation, Methodology, Writing – original draft, Writing – review & editing Affiliation Kirby Institute, University of New South Wales, Sydney, Australia ⨯ * Eva Stadler, Roles Data curation, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review & editing Affiliation Kirby Institute, University of New South Wales, Sydney, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-5129-8180 ](https://orcid.org/0000-0002-5129-8180 "ORCID Registry") ⨯ * Timothy E. Schlub, Roles Formal analysis, Methodology, Visualization, Writing – review & editing Affiliations Kirby Institute, University of New South Wales, Sydney, Australia, Faculty of Medicine and Health, Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-7746-9649 ](https://orcid.org/0000-0001-7746-9649 "ORCID Registry") ⨯ * Shanchita R. Khan, Roles Data curation, Methodology, Writing – review & editing Affiliation Kirby Institute, University of New South Wales, Sydney, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0003-0772-6122 ](https://orcid.org/0000-0003-0772-6122 "ORCID Registry") ⨯ * Claire Xue, Roles Formal analysis, Methodology, Writing – review & editing Affiliation School of Mathematics and Statistics, University of New South Wales, Sydney, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0009-0002-0870-6668 ](https://orcid.org/0009-0002-0870-6668 "ORCID Registry") ⨯ * Stephen J. Kent, Roles Methodology, Visualization, Writing – review & editing Affiliations Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia, Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-8539-4891 ](https://orcid.org/0000-0002-8539-4891 "ORCID Registry") ⨯ * Deborah Cromer , Contributed equally to this work with: Deborah Cromer, Miles P. Davenport, David S. Khoury Roles Conceptualization, Data curation, Methodology, Writing – review & editing Affiliation Kirby Institute, University of New South Wales, Sydney, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-5276-5094 ](https://orcid.org/0000-0002-5276-5094 "ORCID Registry") ⨯ * Miles P. Davenport , Contributed equally to this work with: Deborah Cromer, Miles P. Davenport, David S. Khoury Roles Conceptualization, Methodology, Writing – original draft, Writing – review & editing Affiliation Kirby Institute, University of New South Wales, Sydney, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-4751-1831 ](https://orcid.org/0000-0002-4751-1831 "ORCID Registry") ⨯ * David S. Khoury Contributed equally to this work with: Deborah Cromer, Miles P. Davenport, David S. Khoury Roles Conceptualization, Data curation, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review & editing * E-mail: dkhoury@kirby.unsw.edu.au Affiliation Kirby Institute, University of New South Wales, Sydney, Australia [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0002-2663-1551 ](https://orcid.org/0000-0002-2663-1551 "ORCID Registry") ⨯ # Neutralising antibodies and protection from progression to severe COVID-19: A meta-analysis * Karen M. Elias, * Ainslie Mitchell, * Eva Stadler, * Timothy E. Schlub, * Shanchita R. Khan, * Claire Xue, * Stephen J. Kent, * Deborah Cromer, … * Miles P. Davenport, * David S. Khoury ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: September 2, 2026 * * [Article](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230) * [Authors](https://journals.plos.org/plosmedicine/article/authors?id=10.1371/journal.pmed.1005230) * [Metrics](https://journals.plos.org/plosmedicine/article/metrics?id=10.1371/journal.pmed.1005230) * [Comments](https://journals.plos.org/plosmedicine/article/comments?id=10.1371/journal.pmed.1005230) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pmed.1005230) * [Abstract](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#abstract0) * [Author summary](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#abstract1) * [Introduction](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#sec007) * [Methods](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#sec008) * [Results](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#sec014) * [Discussion](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#sec020) * [Supporting information](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#sec021) * [References](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#references) * [Reader Comments](https://journals.plos.org/plosmedicine/article/comments?id=10.1371/journal.pmed.1005230) * [Figures](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230) ![Accessible Data Icon](https://journals.plos.org/resource/img/accessible_data.svg)Accessible Data [ See the data ![Link Icon](https://journals.plos.org/resource/img/data_link_icon.svg) ](https://doi.org/10.5281/zenodo.21504125) This article includes the Accessible Data icon, an experimental feature to encourage data sharing and reuse. [Find out how research articles qualify for this feature.](https://theplosblog.plos.org/2023/07/accessible-data/) ## Abstract ### Background Vaccine-induced neutralising antibodies are a well-established correlate of protection against acquisition of COVID-19. Vaccine protection from severe COVID-19 remains high, although the role of neutralising antibodies and the contribution of other immune responses to protection from severe outcomes is less clear. Improving understanding of how vaccines prevent severe outcomes is important for future vaccine development. ### Methods and findings Here we undertake a systematic search of the literature to obtain estimates of vaccine protection against progression from SARS-CoV-2 infection to severe COVID-19 (hospital or ICU admission). We aggregate results from 25 published clinical studies of vaccine protection from progression to severe outcomes in people with SARS-CoV-2 infection. We match this clinical data to data from 301 studies of post-vaccination neutralisation titres induced by various vaccines against different SARS-CoV-2 variants from the publicly available Stanford University Coronavirus antiviral and resistance database. We then synthesise the data using meta-regression. Neutralising antibody titres were found to be associated with vaccine protection against progression to severe COVID-19 (relative risk (RR) 0.57 per 10-fold increase in GMT, 95% CI [0.51,0.64], _p_ . **Funding:** This research has been supported by the Commonwealth through an Australian Government Research Training Program (RTP) Scholarship [DOI: ] (to KME). This work is funded by the Australian National Health and Medical Research Council (NHMRC) Investigator Grants 2034282 (to ES), 2016491 (to SJK), 1173528 (to DC), 1173027 (to MPD), 2033318 (to DSK), and Australian Medical Research Future Fund award 2016062 (to SJK, MPD, and DSK). Funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. , . **Competing interests:** The authors declare no competing interests. **Abbreviations:** AICc, Akaike information criterion; aRR, adjusted relative risk; aVE, adjusted vaccine effectiveness; GMT, geometric mean neutralisation titre; RR, relative risk. ## Introduction Vaccination is effective at preventing both symptomatic and severe COVID-19 [[1](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref001)–[3](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref003)]. The immune mechanisms that mediate protection against severe outcomes are a major focus of immunological investigation and improving our understanding of these processes has the potential to guide the development of next generation vaccines that better protect the most vulnerable. However, dissecting the immune responses that are centrally important or directly involved in protection against severe COVID-19 is difficult because correlations do not imply causation and the relatively low frequency of severe disease means large studies are required [[4](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref004),[5](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref005)]. Neutralising antibody titres are predictive of, and sufficient for, protection from symptomatic COVID-19 [[3](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref003),[6](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref006)–[8](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref008)]. That is, neutralising antibodies both correlate with protection against COVID-19 [[3](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref003),[6](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref006),[7](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref007)], and antibodies alone (passively administered as prophylaxis in otherwise naïve individuals) achieve protection against acquisition of COVID-19 at similar antibody levels to that seen in active vaccination [[8](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref008),[9](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref009)]. In the case of severe COVID-19, neutralising antibodies have also been shown to correlate with protection [[10](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref010),[11](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed.1005230.ref011)]. However, since acquiring severe COVD-19 requires first acquiring symptomatic COVID-19, it is perhaps not surprising that neutralising antibodies correlate with protection against severe disease, given they correlate with protection against mild disease ([Fig 1A](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed-1005230-g001) and [1B](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed-1005230-g001)). More relevant to our understanding of immunity against severe COVID-19 is understanding the amount of vaccine-induced protection against _“_ progression _”_ to severe COVID-19 if a breakthrough infection occurs ([Fig 1C](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed-1005230-g001)). That is, if vaccination fails to prevent infection (which often occurs), how well does the vaccine protect people with mild infection from progressing to a more severe event ([Fig 1C](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed-1005230-g001))? Furthermore, is this vaccine-conferred protection against “progression” also correlated with neutralising antibodies (i.e., independent of their role in protection against acquiring mild COVID-19) ([Fig 1A](https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1005230#pmed-1005230-
## Related Clinical Research

- [WHO validates Bhutan for eliminating dog-transmitted human rabies](https://medichelpline.com/clinical-feed/who-0-0-who-validates-bhutan-for-eliminating-dog-transmitted-human-rabies.md)
- [Infection prevention and control implementation during COVID-19 in sub-Saharan Africa: multination](https://medichelpline.com/clinical-feed/bmj-open-0-infection-prevention-and-control-measures-during-the-covid-19-pandemic-in-sub.md)
- [Hepatitis C Prevalence and Care Barriers in Adults with Serious Mental Illness: Updated Systematic](https://medichelpline.com/clinical-feed/bmj-open-6-pooled-prevalence-risk-factors-and-barriers-to-care-for-hepatitis-c-virus-hcv.md)
- [WHO validates Timor-Leste’s elimination of trachoma as a public health problem](https://medichelpline.com/clinical-feed/who-0-0-who-validates-timor-leste-s-elimination-of-trachoma-as-a-public-health-problem.md)
- [Pre-existing Multidimensional Immune Signature Predicts Omicron Infection Risk in Vaccinated Indiv](https://medichelpline.com/clinical-feed/medrxiv-0-a-multidimensional-immune-signature-predicts-susceptibility-to-omicron.md)

## Navigation
- [← Back to Infectious Disease Feed](https://medichelpline.com/clinical-feed/infectious-disease.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.