Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response

Abstract Human respiratory syncytial virus (RSV) is one of the most important causes of severe respiratory tract infections in early childhood. The only prophylactic protection is the neutralizing antibody, palivizumab, which targets a conformational epitope of the RSV fusion (F) protein. The F prot...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kristina Borochova, Katarzyna Niespodziana, Margarete Focke-Tejkl, Gerhard Hofer, Walter Keller, Rudolf Valenta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ecbded56057f4d7db2a7a415ea38bb6a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ecbded56057f4d7db2a7a415ea38bb6a
record_format	dspace
spelling	oai:doaj.org-article:ecbded56057f4d7db2a7a415ea38bb6a2021-12-02T14:11:30ZDissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response10.1038/s41598-021-82893-y2045-2322https://doaj.org/article/ecbded56057f4d7db2a7a415ea38bb6a2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82893-yhttps://doaj.org/toc/2045-2322Abstract Human respiratory syncytial virus (RSV) is one of the most important causes of severe respiratory tract infections in early childhood. The only prophylactic protection is the neutralizing antibody, palivizumab, which targets a conformational epitope of the RSV fusion (F) protein. The F protein is generated as a F0 precursor containing two furin cleavage sites allowing excision of the P27 fragment and then gives rise to a fusion-competent version consisting of the N-terminal F2 subunit and the a C-terminal F1 subunits linked by two disulphide bonds. To investigate natural human F-specific antibody responses, F2 conferring the species-specificity of RSV, was expressed in Escherichia coli. Furthermore, the F0 protein, comprising both subunits F2 and F1, was expressed as palivizumab-reactive glycoprotein in baculovirus-infected insect cells. Six overlapping F2-derived peptides lacking secondary structure were synthesized. The analysis of IgG, IgA and IgM responses of adult subjects to native versions and denatured forms of F2 and F0 and to unfolded F2-derived peptides revealed that mainly non-conformational F epitopes, some of which represented cryptic epitopes which are not exposed on the proteins were recognized. Furthermore, we found a dissociation of IgG, IgA and IgM antibody responses to F epitopes with F2 being a major target for the F-specific IgM response. The scattered and dissociated immune response to F may explain why the natural RSV-specific antibody response is only partially protective underlining the need for vaccines focusing human antibody responses towards neutralizing RSV epitopes.Kristina BorochovaKatarzyna NiespodzianaMargarete Focke-TejklGerhard HoferWalter KellerRudolf ValentaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kristina Borochova Katarzyna Niespodziana Margarete Focke-Tejkl Gerhard Hofer Walter Keller Rudolf Valenta Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response
description	Abstract Human respiratory syncytial virus (RSV) is one of the most important causes of severe respiratory tract infections in early childhood. The only prophylactic protection is the neutralizing antibody, palivizumab, which targets a conformational epitope of the RSV fusion (F) protein. The F protein is generated as a F0 precursor containing two furin cleavage sites allowing excision of the P27 fragment and then gives rise to a fusion-competent version consisting of the N-terminal F2 subunit and the a C-terminal F1 subunits linked by two disulphide bonds. To investigate natural human F-specific antibody responses, F2 conferring the species-specificity of RSV, was expressed in Escherichia coli. Furthermore, the F0 protein, comprising both subunits F2 and F1, was expressed as palivizumab-reactive glycoprotein in baculovirus-infected insect cells. Six overlapping F2-derived peptides lacking secondary structure were synthesized. The analysis of IgG, IgA and IgM responses of adult subjects to native versions and denatured forms of F2 and F0 and to unfolded F2-derived peptides revealed that mainly non-conformational F epitopes, some of which represented cryptic epitopes which are not exposed on the proteins were recognized. Furthermore, we found a dissociation of IgG, IgA and IgM antibody responses to F epitopes with F2 being a major target for the F-specific IgM response. The scattered and dissociated immune response to F may explain why the natural RSV-specific antibody response is only partially protective underlining the need for vaccines focusing human antibody responses towards neutralizing RSV epitopes.
format	article
author	Kristina Borochova Katarzyna Niespodziana Margarete Focke-Tejkl Gerhard Hofer Walter Keller Rudolf Valenta
author_facet	Kristina Borochova Katarzyna Niespodziana Margarete Focke-Tejkl Gerhard Hofer Walter Keller Rudolf Valenta
author_sort	Kristina Borochova
title	Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response
title_short	Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response
title_full	Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response
title_fullStr	Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response
title_full_unstemmed	Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response
title_sort	dissociation of the respiratory syncytial virus f protein-specific human igg, iga and igm response
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ecbded56057f4d7db2a7a415ea38bb6a
work_keys_str_mv	AT kristinaborochova dissociationoftherespiratorysyncytialvirusfproteinspecifichumaniggigaandigmresponse AT katarzynaniespodziana dissociationoftherespiratorysyncytialvirusfproteinspecifichumaniggigaandigmresponse AT margaretefocketejkl dissociationoftherespiratorysyncytialvirusfproteinspecifichumaniggigaandigmresponse AT gerhardhofer dissociationoftherespiratorysyncytialvirusfproteinspecifichumaniggigaandigmresponse AT walterkeller dissociationoftherespiratorysyncytialvirusfproteinspecifichumaniggigaandigmresponse AT rudolfvalenta dissociationoftherespiratorysyncytialvirusfproteinspecifichumaniggigaandigmresponse
_version_	1718391879201980416

Dissociation of the respiratory syncytial virus F protein-specific human IgG, IgA and IgM response

Ejemplares similares