Epitope mapping of antibodies induced with a conserved rhinovirus protein generating protective anti-rhinovirus immunity
File(s)
Supporting information
Accepted version
Author(s)
Type
Journal Article
Abstract
Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations. Currently there is no vaccine for RV which is largely due to the existence of ∼160 serotypes/strains. We demonstrated previously that immunising mice with highly conserved VP4 and VP2 regions of the RV polyprotein (RV-A16 VP0) generated cross-reactive immunity to RV in vivo. The current study investigated and mapped the epitopes of RV-A16 VP0 that are targets for antibodies in serum samples from VP0 immunisation and RV challenge studies in mice. Recombinant capsid proteins, peptide pools and individual peptides spanning the immunogen sequence (RV-A16 VP0) were assessed for IgG binding sites to identify epitopes. We found that peptide pools covering the C-terminus of VP4, the N-terminus of VP2 and the neutralising NIm-II site within VP2 were bound by serum IgG from immunised mice. The NIm-II site peptide pool blocked IgG binding to the immunogen RV-A16 VP0 and individual peptides within the pool binding IgG were further mapped. Thus, we have identified immunodominant epitopes of RV vaccine candidate RV-A16 VP0, noting that strong IgG binding antibodies were observed that target a key neutralising epitope that is highly variable amongst RV serotypes.
Date Issued
2019-05-09
Date Acceptance
2019-04-09
Citation
Vaccine, 2019, 37 (21), pp.2805-2813
ISSN
0264-410X
Publisher
Elsevier
Start Page
2805
End Page
2813
Journal / Book Title
Vaccine
Volume
37
Issue
21
Copyright Statement
© 2019 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.
Sponsor
Commission of the European Communities
Asthma UK
Commission of the European Communities
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000468710400006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
233015
Asthma UK Centre
260895
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
Rhinovirus
Subunit vaccine
Antibodies
Epitope
Neutralisation
NEUTRALIZING ANTIBODY
MONOCLONAL-ANTIBODIES
NUMBERING SYSTEM
CAPSID PROTEIN
VACCINE
INFECTION
CELLS
RECEPTOR
PEPTIDE
VIRUS
Publication Status
Published
Date Publish Online
2019-04-16