Evidence map›Paper›PMID 21937658›Full record

ArticleJournal of virology2011

A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge.

Meagan Bolles, Damon Deming, Kristin Long, Sudhakar Agnihothram, Alan Whitmore, Martin Ferris, William Funkhouser, Lisa Gralinski, Allison Totura, Mark Heise and 1 more

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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 333 papers.

0numbers the graph read from it
0cells of the map it votes in
333citing papers in PubMed
4.6field-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

333 citing papers in PubMed, 501 citations in OpenAlex.

  1. 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
  2. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.The New England journal of medicine · 2021
    Trial
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273 more citing papers are in PubMed but not listed here.

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 at 1 institution in 1 country.

Meagan BollesDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Damon Deming
Kristin Long
Sudhakar Agnihothram
Alan Whitmore
Martin Ferris
William Funkhouser
Lisa Gralinski
Allison Totura
Mark Heise
Ralph S Baric
University of North Carolina at Chapel Hill · US

Funding

The Burden of Chikungunya and Dengue Infection in KenyaU54AI081680 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI RYMAN, KATHERINE D · 2009 to 2013
$40.4M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008719 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DARVILLE, TONI, DESHMUKH, MOHANISH P · 1999 to 2023
$15.1M
SARS-CoV Pathogenic Mechanisms in Senescent MiceR01AI075297 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S · 2008 to 2012
$2.5M
NIAID NIH HHS AI075297NIAID NIH HHS R01 AI075297NIAID NIH HHS U54AI080680NIAID NIH HHS U54 AI081680NIAID NIH HHS U54AI081680-01NIGMS NIH HHS T32 GM008719NIGMS NIH HHS T32GM008719
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.

Indexed as

AnimalsAntibodies, ViralBlotting, WesternChlorocebus aethiopsEnzyme-Linked Immunosorbent AssayFemaleLungMiceMice, Inbred BALB CNeutralization TestsPulmonary EosinophiliaReal-Time Polymerase Chain ReactionRNA, MessengerSevere Acute Respiratory SyndromeSevere acute respiratory syndrome-related coronavirusVaccinationAntibodies, ViralRNA, MessengerVaccines, InactivatedViral Envelope ProteinsViral Vaccines

Identifiers

PMID21937658
PMCPMC3209347
OpenAlexW1995367098

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.