Evidence map›Paper›PMID 25240756›Full record

ArticleVaccine2014

Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments--the importance of immunofocusing in subunit vaccine design.

Cuiqing Ma, Lili Wang, Xinrong Tao, Naru Zhang, Yang Yang, Chien-Te K Tseng, Fang Li, Yusen Zhou, Shibo Jiang, Lanying Du

Abstract read
In one paragraph

Article in Vaccine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

105 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Immunofocusing design of a fusion glycoprotein monomer vaccine for respiratory syncytial virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Advances in mRNA and other vaccines against MERS-CoV.Translational research : the journal of laboratory and clinical medicine · 2022
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

45 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

10 authors.

Cuiqing Ma *Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Lili Wang *Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Xinrong TaoDepartment of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.
Naru ZhangLindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Yang YangDepartment of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
Chien-Te K TsengDepartment of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.
Fang LiDepartment of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
Yusen ZhouState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Shibo JiangLindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Lanying DuLindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.

Funding

Receptor recognition mechanisms of coronavirusesR01AI089728 · NIAID · UNIVERSITY OF MINNESOTA · PI Fang Li, Timothy Patrick Sheahan · 2010 to 2026
$4.7M
Critical neutralizing domain-based vaccines against new SARS-like virus hCoV-EMCR21AI109094 · NIAID · NEW YORK BLOOD CENTER · PI DU, LANYING · 2014 to 2015
$466k
NIAID NIH HHS R01 AI089728NIAID NIH HHS R01AI089728NIAID NIH HHS R21 AI109094NIAID NIH HHS R21AI109094
6 · The paper itself

Abstract

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential. The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".

Indexed as

Middle East Respiratory Syndrome CoronavirusAnimalsAntibodies, NeutralizingAntibodies, ViralAntigens, ViralCoronavirus InfectionsFemaleHumansImmunoglobulin Fc FragmentsImmunoglobulin GMice, Inbred BALB CNeutralization TestsRabbitsReceptors, CoronavirusReceptors, VirusSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralAntigens, ViralImmunoglobulin Fc FragmentsImmunoglobulin GReceptors, CoronavirusReceptors, VirusSpike Glycoprotein, CoronavirusVaccines, SubunitViral VaccinesCritical neutralizing domainImmunofocusingMERSMERS-CoVReceptor-binding domainSpike protein

Identifiers

PMID25240756
PMCPMC4194190

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.