Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization

被引:21
作者
Leemans, Annelies [1 ]
Boeren, Marlies [1 ]
Van der Gucht, Winke [1 ]
Pintelon, Isabel [2 ]
Roose, Kenny [3 ,4 ]
Schepens, Bert [3 ,4 ]
Saelens, Xavier [3 ,4 ]
Bailey, Dalan [5 ]
Martinet, Wim [6 ]
Caljon, Guy [1 ]
Maes, Louis [1 ]
Cos, Paul [1 ]
Delputte, Peter [1 ]
机构
[1] Univ Antwerp, Lab Microbiol Parasitol & Hyg, B-2610 Antwerp, Belgium
[2] Univ Antwerp, Lab Cell Biol & Histol, B-2610 Antwerp, Belgium
[3] VIB, Med Biotechnol Ctr, B-9052 Ghent, Belgium
[4] Univ Ghent, Dept Biomed Mol Biol, B-9052 Ghent, Belgium
[5] Pirbright Inst, Surrey GU24 0NF, England
[6] Univ Antwerp, Lab Physiopharmacol, B-2610 Antwerp, Belgium
来源
VIRUSES-BASEL | 2018年 / 10卷 / 08期
基金
英国生物技术与生命科学研究理事会;
关键词
class I fusion protein; virus glycosylation; DNA immunization; humoral responses; pneumovirus; vaccine; WEST NILE VIRUS; LINKED GLYCANS; MEMBRANE-FUSION; CELL-FUSION; F-PROTEIN; IN-VITRO; NEUTRALIZING ANTIBODY; MONOCLONAL-ANTIBODY; ENVELOPE PROTEINS; REVERSE GENETICS;
D O I
10.3390/v10080426
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Prevention of severe lower respiratory tract infections in infants caused by the human respiratory syncytial virus (hRSV) remains a major public health priority. Currently, the major focus of vaccine development relies on the RSV fusion (F) protein since it is the main target protein for neutralizing antibodies induced by natural infection. The protein conserves 5 N-glycosylation sites, two of which are located in the F2 subunit (N27 and N70), one in the F1 subunit (N500) and two in the p27 peptide (N116 and N126). To study the influence of the loss of one or more N-glycosylation sites on RSV F immunogenicity, BALB/c mice were immunized with plasmids encoding RSV F glycomutants. In comparison with F WT DNA immunized mice, higher neutralizing titres were observed following immunization with F N116Q. Moreover, RSV A2-K-line19F challenge of mice that had been immunized with mutant F N116Q DNA was associated with lower RSV RNA levels compared with those in challenged WT F DNA immunized animals. Since p27 is assumed to be post-translationally released after cleavage and thus not present on the mature RSV F protein, it remains to be elucidated how deletion of this glycan can contribute to enhanced antibody responses and protection upon challenge. These findings provide new insights to improve the immunogenicity of RSV F in potential vaccine candidates.
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页数:20
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共 68 条
[1]   Taxonomy of the order Mononegavirales: update 2016 [J].
Afonso, Claudio L. ;
Amarasinghe, Gaya K. ;
Banyai, Krisztian ;
Bao, Yiming ;
Basler, Christopher F. ;
Bavari, Sina ;
Bejerman, Nicolas ;
Blasdell, Kim R. ;
Briand, Francois-Xavier ;
Briese, Thomas ;
Bukreyev, Alexander ;
Calisher, Charles H. ;
Chandran, Kartik ;
Cheng, Jiasen ;
Clawson, Anna N. ;
Collins, Peter L. ;
Dietzgen, Ralf G. ;
Dolnik, Olga ;
Domier, Leslie L. ;
Duerrwald, Ralf ;
Dye, John M. ;
Easton, Andrew J. ;
Ebihara, Hideki ;
Farkas, Szilvia L. ;
Freitas-Astua, Juliana ;
Formenty, Pierre ;
Fouchier, Ron A. M. ;
Fu, Yanping ;
Ghedin, Elodie ;
Goodin, Michael M. ;
Hewson, Roger ;
Horie, Masayuki ;
Hyndman, Timothy H. ;
Jiang, Daohong ;
Kitajima, Elliot W. ;
Kobinger, Gary P. ;
Kondo, Hideki ;
Kurath, Gael ;
Lamb, Robert A. ;
Lenardon, Sergio ;
Leroy, Eric M. ;
Li, Ci-Xiu ;
Lin, Xian-Dan ;
Liu, Lijiang ;
Longdon, Ben ;
Marton, Szilvia ;
Maisner, Andrea ;
Muhlberger, Elke ;
Netesov, Sergey V. ;
Nowotny, Norbert .
ARCHIVES OF VIROLOGY, 2016, 161 (08) :2351-2360
[2]   Dual Split Protein-Based Fusion Assay Reveals that Mutations to Herpes Simplex Virus (HSV) Glycoprotein gB Alter the Kinetics of Cell-Cell Fusion Induced by HSV Entry Glycoproteins [J].
Atanasiu, Doina ;
Saw, Wan Ting ;
Gallagher, John R. ;
Hannah, Brian P. ;
Matsuda, Zene ;
Whitbeck, J. Charles ;
Cohen, Gary H. ;
Eisenberg, Roselyn J. .
JOURNAL OF VIROLOGY, 2013, 87 (21) :11332-11345
[3]   Influence of N-linked glycans on intracellular transport of hepatitis C virus E1 chimeric glycoprotein and its role in pseudotype virus infectivity [J].
Beyene, A ;
Basu, A ;
Meyer, K ;
Ray, R .
VIROLOGY, 2004, 324 (02) :273-285
[4]   Respiratory Syncytial Virus-A Comprehensive Review [J].
Borchers, Andrea T. ;
Chang, Christopher ;
Gershwin, M. Eric ;
Gershwin, Laurel J. .
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY, 2013, 45 (03) :331-379
[5]  
CASH P, 1979, VIROLOGY, V92, P375, DOI 10.1016/0042-6822(79)90142-9
[6]   Role of N-linked glycosylation of the human parainfluenza virus type 3 hemagglutinin-neuraminidase protein [J].
Chu, Fu-lu ;
Wen, Hong-ling ;
Hou, Gui-hua ;
Lin, Bin ;
Zhang, Wen-qiang ;
Song, Yan-yan ;
Ren, Gui-jie ;
Sun, Cheng-xi ;
Li, Zhen-mei ;
Wang, Zhiyu .
VIRUS RESEARCH, 2013, 174 (1-2) :137-147
[7]   Viral and host factors in human respiratory syncytial virus pathogenesis [J].
Collins, Peter L. ;
Graham, Barney S. .
JOURNAL OF VIROLOGY, 2008, 82 (05) :2040-2055
[8]   Progress in understanding and controlling respiratory syncytial virus: Still crazy after all these years [J].
Collins, Peter L. ;
Melero, Jose A. .
VIRUS RESEARCH, 2011, 162 (1-2) :80-99
[9]   POSTTRANSLATIONAL PROCESSING AND OLIGOMERIZATION OF THE FUSION GLYCOPROTEIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS [J].
COLLINS, PL ;
MOTTET, G .
JOURNAL OF GENERAL VIROLOGY, 1991, 72 :3095-3101
[10]   Cross-neutralization of four paramyxoviruses by a human monoclonal antibody [J].
Corti, Davide ;
Bianchi, Siro ;
Vanzetta, Fabrizia ;
Minola, Andrea ;
Perez, Laurent ;
Agatic, Gloria ;
Guarino, Barbara ;
Silacci, Chiara ;
Marcandalli, Jessica ;
Marsland, Benjamin J. ;
Piralla, Antonio ;
Percivalle, Elena ;
Sallusto, Federica ;
Baldanti, Fausto ;
Lanzavecchia, Antonio .
NATURE, 2013, 501 (7467) :439-+