Correction: Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus
Open accessAbstract
Background: Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control.Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated.Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a viruslike-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologictype lung disease.Design: Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein.Balb/c or C57BL/6 mice were vaccinated IM on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56.On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology.Results: All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses.Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV.All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all.Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains.The pathologic changes seen in all control groups lacked the eosinophil prominence.Conclusions: These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV.However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced.Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.
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Previous reports on SARS and MERS vaccine candidates raised concerns about pulmonary immunopathology caused by Th2 response or ADE.
“Previous reports on the development of SARS and MERS vaccine candidates raised concerns about pulmonary immunopathology, either directly caused by a type 2 helper T-cell (Th2) response or as a result of ADE (4, 14, 15).”
From Development of an inactivated vaccine candidate for SARS-CoV-2 (2020) · cites this paper as [14]
The Discussion (page unavailable) reports Th2-type lung immunopathology after vaccinated animals were challenged with SARS-CoV, supporting the concern about SARS vaccine candidates. It discusses antibody-mediated disease enhancement in a feline coronavirus infection, but does not establish ADE as the cause of pulmonary immunopathology from SARS vaccines; it does not address MERS vaccine candidates. (LLM, conf=0.88)
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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., Diemert, D., Spector, S. A., Rouphael, N., Creech, C. B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2035389 · Cited by 10,119 · see citing works
Development of an inactivated vaccine candidate for SARS-CoV-2
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- Authors
- Tseng, C.-T., Sbrana, E., Iwata-Yoshikawa, N., Newman, P. C., Garron, T., Atmar, R. L., Peters, C. J., & Couch, R. B.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Baylor College of Medicine (US)
- Corresponding author
- Couch, Robert B.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-08-09
- Volume
- 7
- Issue
- 8
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3436093
- OpenAlex
- W4206708282
- Cited by
- 122
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 18 · 2021: 44 · 2020: 39 · 2019: 1 · 2017: 1 · 2015: 1
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health and Human Services
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- SARS-CoV, SARS vaccine, pulmonary immunopathology, eosinophil infiltration, virus-like particle vaccine, inactivated whole virus vaccine, alum adjuvant, neutralizing antibodies, vaccine safety, mouse model
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