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Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein

Bert Schepens UGent, Koen Sedeyn UGent, Liesbeth Vande Ginste, Sarah De Baets UGent, Michael Schotsaert, Kenny Roose UGent, Lieselot Houspie, Marc Van Ranst, Barbara Gilbert UGent, Nico van Rooijen, et al. (2014) EMBO MOLECULAR MEDICINE. 6(11). p.1436-1454
abstract
Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
vaccine, small hydrophobic protein, DEPENDENT CELLULAR CYTOTOXICITY, NATURAL-KILLER-CELLS, FC-GAMMA RECEPTORS, NEUTRALIZING ANTIBODIES, FUSION GLYCOPROTEIN, MONOCLONAL-ANTIBODY, SYSTEMATIC ANALYSIS, HUMORAL IMMUNITY, DENDRITIC CELLS, YOUNG-CHILDREN, Fc receptor, alveolar macrophages, human respiratory syncytial virus
journal title
EMBO MOLECULAR MEDICINE
EMBO Mol. Med.
volume
6
issue
11
pages
1436 - 1454
Web of Science type
Article
Web of Science id
000344555200006
JCR category
MEDICINE, RESEARCH & EXPERIMENTAL
JCR impact factor
8.665 (2014)
JCR rank
9/123 (2014)
JCR quartile
1 (2014)
ISSN
1757-4676
DOI
10.15252/emmm.201404005
language
English
UGent publication?
yes
classification
A1
copyright statement
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
id
5839224
handle
http://hdl.handle.net/1854/LU-5839224
date created
2015-02-05 15:33:25
date last changed
2017-03-07 10:41:10
@article{5839224,
  abstract     = {Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection.},
  author       = {Schepens, Bert and Sedeyn, Koen and Vande Ginste, Liesbeth and De Baets, Sarah and Schotsaert, Michael and Roose, Kenny and Houspie, Lieselot and Van Ranst, Marc and Gilbert, Barbara and van Rooijen, Nico and Fiers, Walter and Piedra, Pedro and Saelens, Xavier},
  issn         = {1757-4676},
  journal      = {EMBO MOLECULAR MEDICINE},
  keyword      = {vaccine,small hydrophobic protein,DEPENDENT CELLULAR CYTOTOXICITY,NATURAL-KILLER-CELLS,FC-GAMMA RECEPTORS,NEUTRALIZING ANTIBODIES,FUSION GLYCOPROTEIN,MONOCLONAL-ANTIBODY,SYSTEMATIC ANALYSIS,HUMORAL IMMUNITY,DENDRITIC CELLS,YOUNG-CHILDREN,Fc receptor,alveolar macrophages,human respiratory syncytial virus},
  language     = {eng},
  number       = {11},
  pages        = {1436--1454},
  title        = {Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein},
  url          = {http://dx.doi.org/10.15252/emmm.201404005},
  volume       = {6},
  year         = {2014},
}

Chicago
Schepens, Bert, Koen Sedeyn, Liesbeth Vande Ginste, Sarah De Baets, Michael Schotsaert, Kenny Roose, Lieselot Houspie, et al. 2014. “Protection and Mechanism of Action of a Novel Human Respiratory Syncytial Virus Vaccine Candidate Based on the Extracellular Domain of Small Hydrophobic Protein.” Embo Molecular Medicine 6 (11): 1436–1454.
APA
Schepens, B., Sedeyn, K., Vande Ginste, L., De Baets, S., Schotsaert, M., Roose, K., Houspie, L., et al. (2014). Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein. EMBO MOLECULAR MEDICINE, 6(11), 1436–1454.
Vancouver
1.
Schepens B, Sedeyn K, Vande Ginste L, De Baets S, Schotsaert M, Roose K, et al. Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein. EMBO MOLECULAR MEDICINE. 2014;6(11):1436–54.
MLA
Schepens, Bert, Koen Sedeyn, Liesbeth Vande Ginste, et al. “Protection and Mechanism of Action of a Novel Human Respiratory Syncytial Virus Vaccine Candidate Based on the Extracellular Domain of Small Hydrophobic Protein.” EMBO MOLECULAR MEDICINE 6.11 (2014): 1436–1454. Print.