Vaccine-Associated Enhanced Disease and Pathogenic Human Coronaviruses

Cillian Gartlan*, Tom Tipton, Francisco J. Salguero, Quentin Sattentau, Andrew Gorringe, Miles W. Carroll

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

32 Citations (Scopus)
15 Downloads (Pure)


Vaccine-associated enhanced disease (VAED) is a difficult phenomenon to define and can be confused with vaccine failure. Using studies on respiratory syncytial virus (RSV) vaccination and dengue virus infection, we highlight known and theoretical mechanisms of VAED, including antibody-dependent enhancement (ADE), antibody-enhanced disease (AED) and Th2-mediated pathology. We also critically review the literature surrounding this phenomenon in pathogenic human coronaviruses, including MERS-CoV, SARS-CoV-1 and SARS-CoV-2. Poor quality histopathological data and a lack of consistency in defining severe pathology and VAED in preclinical studies of MERS-CoV and SARS-CoV-1 vaccines in particular make it difficult to interrogate potential cases of VAED. Fortuitously, there have been only few reports of mild VAED in SARS-CoV-2 vaccination in preclinical models and no observations in their clinical use. We describe the problem areas and discuss methods to improve the characterisation of VAED in the future.

Original languageEnglish
Article number882972
JournalFrontiers in Immunology
Publication statusPublished - 4 Apr 2022

Bibliographical note

Funding Information: TT and MC were funded by the US Food and Drug Administration 75F40120C00085: Characterization of severe coronavirus infection
in humans and model systems for MCM development and evaluation. TT and MC were also funded by a grant from the Coalition for Epidemic Preparedness Innovations (CEPI): Applying systems immunology to NHP COVID-19 vaccine challenge study data sets to define Correlates of Protection to SARS-CoV-2.

Open Access: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Publisher Copyright: Copyright © 2022 Gartlan, Tipton, Salguero, Sattentau, Gorringe and Carroll.

Citation: Gartlan C, Tipton T, Salguero FJ, Sattentau Q, Gorringe A and Carroll MW
(2022) Vaccine-Associated Enhanced Disease and Pathogenic Human Coronaviruses. Front. Immunol. 13:882972.

DOI: 10.3389/fimmu.2022.882972


  • COVID-19
  • SARS-CoV-2
  • coronavirus
  • enhancement
  • safety
  • vaccine
  • vaccine-associated enhanced disease


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