Evidence map›Paper›PMID 22536382›Full record

ArticlePloS one2012

Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus.

Chien-Te Tseng, Elena Sbrana, Naoko Iwata-Yoshikawa, Patrick C Newman, Tania Garron, Robert L Atmar, Clarence J Peters, Robert B Couch

Erratum issued Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04934111 (A Clinical Trial to Assess the Safety and Immunogenicity of LNP-nCOV saRNA-02, a Self-amplifying Ribonucleic Acid), which is not on this map. Cited by 396 papers.

0numbers the graph read from it
0cells of the map it votes in
396citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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.

NCT04934111 phase1unknown statusnot on this mapstarted 2021, after this paper: background citation

A Clinical Trial to Assess the Safety and Immunogenicity of LNP-nCOV saRNA-02, a Self-amplifying Ribonucleic Acid (saRNA) Vaccine, in SARS-CoV-2 Seronegative and Seropositive Uganda Population

TypeinterventionalSponsorMRC/UVRI and LSHTM Uganda Research UnitRan2021 to 2022Enrolled42ConditionsCOVID-19ArmsLNP-nCOV saRNA-02 Vaccine
3 · Its place in the literature

Who cites it

396 citing papers in PubMed, 606 citations in OpenAlex.

  1. Trial
  2. A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Trial
  3. Trial
  4. Trial
  5. Trial
  6. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.The New England journal of medicine · 2021
    Trial
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
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  19. Review
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336 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Chien-Te TsengDepartment of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, United States of America.
Elena Sbrana
Naoko Iwata-Yoshikawa
Patrick C Newman
Tania Garron
Robert L Atmar
Clarence J Peters
Robert B Couch
The University of Texas Medical Branch at Galveston · USBaylor College of Medicine · US

Funding

VIRAL RESPIRATORY PATHOGENS RESEARCH UNIT (VRPRU)N01AI30039 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI COUCH, ROBERT B · 2007 to 2012
$12.0M
VIRAL RESPIRATORY PATHOGENS RESEARCH UNIT /VRPRU/-266030039-266030039N01AI030039 · NIAID · BAYLOR COLLEGE OF MEDICINE INC · PI COUCH, ROBERT B. · 2003 to 2006
–
NIAID NIH HHS N01 AI030039NIAID NIH HHS N01 AI 30039
6 · The paper itself

Abstract

backgroundSevere 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 virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.

designFour 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 i.m. 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.

resultsAll 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.

conclusionsThese 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.

Indexed as

AnimalsChlorocebus aethiopsEosinophilsFemaleLungMiceMice, Inbred BALB CMice, Inbred C57BLSevere Acute Respiratory SyndromeSevere acute respiratory syndrome-related coronavirusTh2 CellsTissue Culture TechniquesVaccinationVaccines, InactivatedVero CellsViral Envelope ProteinsVaccines, InactivatedViral Envelope ProteinsViral Vaccines

Identifiers

PMID22536382
PMCPMC3335060
OpenAlexW2095633747

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.