Evidence map›Paper›PMID 33952638›Full record

ArticleJournal of virology2021

Second-Generation Live-Attenuated Candid#1 Vaccine Virus Resists Reversion and Protects against Lethal Junín Virus Infection in Guinea Pigs.

Brian B Gowen, Brady T Hickerson, Joanne York, Jonna B Westover, Eric J Sefing, Kevin W Bailey, Luci Wandersee, Jack H Nunberg

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 12% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
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  13. Strategies of rational and structure-driven vaccine design for Arenaviruses.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2024
    Review
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  17. Structural and molecular biology of Sabiá virus.Experimental biology and medicine (Maywood, N.J.) · 2023
    Review
  18. Review
  19. Lassa Virus Countermeasures.Current topics in microbiology and immunology · 2023
    Article
  20. Review
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

8 authors at 2 institutions in 1 country.

Brian B GowenDepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Brady T Hickerson *Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Joanne York *Montana Biotechnology Center, University of Montana, Missoula, Montana, USA.
Jonna B Westover *Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Eric J SefingDepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Kevin W BaileyDepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Luci WanderseeDepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Jack H NunbergMontana Biotechnology Center, University of Montana, Missoula, Montana, USA.
Utah State University · USUniversity of Montana · US

Funding

Structure-function studies of the tripartite Junin arenavirus GP-CR01AI074818 · NIAID · UNIVERSITY OF MONTANA · PI NUNBERG, JACK H · 2008 to 2012
$1.6M
Rational design of a safe recombinant Candid#1 vaccineR01AI150950 · NIAID · UNIVERSITY OF MONTANA · PI NUNBERG, JACK H · 2021 to 2024
$1.5M
Intersubunit crosstalk in the tripartite arenavirus envelope glycoproteinR15AI119803 · NIAID · UNIVERSITY OF MONTANA · PI NUNBERG, JACK H · 2016 to 2016
$427k
Design and development of a safe recombinant Candid#1 vaccineR56AI136467 · NIAID · UNIVERSITY OF MONTANA · PI NUNBERG, JACK H · 2019 to 2019
$374k
HHS | National Institutes of Health (NIH) AI074818HHS | National Institutes of Health (NIH) HHSN2272201700041INIAID NIH HHS HHSN272201700041INIAID NIH HHS R01 AI074818NIAID NIH HHS R01 AI150950NIAID NIH HHS R15 AI119803NIAID NIH HHS R56 AI136467
6 · The paper itself

Abstract

Live-attenuated virus vaccines are highly effective in preventing viral disease but carry intrinsic risks of residual virulence and reversion to pathogenicity. The classically derived Candid#1 virus protects seasonal field workers in Argentina against zoonotic infection by Junín virus (JUNV) but is not approved in the United States, in part due to the potential for reversion at the attenuating locus, a phenylalanine-to-isoleucine substitution at position 427 in the GP2 subunit of the GPC envelope glycoprotein. Previously, we demonstrated facile reversion of recombinant Candid#1 (rCan) in cell culture and identified an epistatic interaction between the attenuating I427 and a secondary K33S mutation in the stable signal peptide (SSP) subunit of GPC that imposes an evolutionary barrier to reversion. The magnitude of this genetic barrier is manifest in our repeated failures to rescue the hypothetical revertant virus. In this study, we show that K33S rCan is safe and attenuated in guinea pigs and capable of eliciting potent virus-neutralizing antibodies. Immunized animals are fully protected against lethal challenge with virulent JUNV. In addition, we employed a more permissive model of infection in neonatal mice to investigate genetic reversion. RNA sequence analysis of the recovered virus identified revertant viruses in pups inoculated with the parental rCan virus and none in mice receiving K33S rCan (

Indexed as

AnimalsAntibodies, ViralChlorocebus aethiopsGuinea PigsHemorrhagic Fever, AmericanImmunogenicity, VaccineJunin virusMaleVaccines, AttenuatedVaccines, SyntheticVero CellsViral VaccinesVirulenceAntibodies, ViralVaccines, AttenuatedVaccines, SyntheticViral VaccinesarenavirusattenuationevolutionJunín viruslive-attenuated vaccinereversion

Identifiers

PMID33952638
PMCPMC8223921
OpenAlexW3157745825

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.