High-Titre Neutralizing Antibodies to H1N1 Influenza Virus after Mouse Immunization with Yeast Expressed H1 Antigen: A Promising Influenza Vaccine Candidate

被引:1
作者
Kopera, Edyta [1 ]
Zdanowski, Konrad [1 ,2 ]
Uranowska, Karolina [3 ,4 ]
Kosson, Piotr [5 ]
Saczynska, Violetta [6 ]
Florys, Katarzyna [6 ]
Szewczyk, Boguslaw [3 ,4 ]
机构
[1] Polish Acad Sci, Inst Biochem & Biophys, Pawinskiego 5A, PL-02106 Warsaw, Poland
[2] Univ Nat Sci & Humanities, Inst Chem, 3 Maja 54, PL-08110 Siedlce, Poland
[3] Univ Gdansk, Intercoll Fac Biotechnol, Dept Recombinant Vaccines, Abrahama 58, PL-80307 Gdansk, Poland
[4] Med Univ Gdansk, Abrahama 58, PL-80307 Gdansk, Poland
[5] Polish Acad Sci, Mossakowski Med Res Ctr, Pawinskiego 5, PL-02106 Warsaw, Poland
[6] Inst Biotechnol & Antibiot, Staroscinska 5, PL-02516 Warsaw, Poland
关键词
HEMAGGLUTININ PROTEIN; IMMUNOGENICITY; GLYCOSYLATION; DOMAIN; CELLS; MICE;
D O I
10.1155/2019/2463731
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
H1N1 influenza virus is still regarded as a serious pandemic threat. The most effective method of protection against influenza virus and the way to reduce the risk of epidemic or pandemic spread is vaccination. Influenza vaccine manufactured in a traditional way, though well developed, has some drawbacks and limitations which have stimulated interest in developing alternative approaches. In this study, we demonstrate that the recombinant H1 vaccine based on the hydrophilic haemagglutinin (HA) domain and produced in the yeast system elicited high titres of serum haemagglutination-inhibiting antibodies in mice. Transmission electron microscopy showed that H1 antigen oligomerizes into functional higher molecular forms similar to rosette-like structures. Analysis of the N-linked glycans using mass spectrometry revealed that the H1 protein is glycosylated at the same sites as the native HA. The recombinant antigen was secreted into a culture medium reaching approximately 10mg/l. These results suggest that H1 produced in Pichia pastoris can be considered as the vaccine candidate against H1N1 virus.
引用
收藏
页数:10
相关论文
共 27 条
[1]   Influence of copy number on the expression levels of pandemic influenza hemagglutinin recombinant protein in methylotrophic yeast Pichia pastoris [J].
Athmaram, T. N. ;
Saraswat, Shweta ;
Singh, Anil Kumar ;
Rao, M. Kameswara ;
Gopalan, N. ;
Suryanarayana, V. V. S. ;
Rao, P. V. L. .
VIRUS GENES, 2012, 45 (03) :440-451
[2]   Yeast expressed recombinant Hemagglutinin protein of Novel H1N1 elicits neutralising antibodies in rabbits and mice [J].
Athmaram, T. N. ;
Saraswat, Shweta ;
Santhosh, S. R. ;
Singh, Anil Kumar ;
Suryanarayana, V. V. S. ;
Priya, Raj ;
Gopalan, N. ;
Parida, Manmohan ;
Rao, P. V. Lakshmana ;
Vijayaraghavan, R. .
VIROLOGY JOURNAL, 2011, 8
[3]  
Bizanov G, 2005, SCAND J LAB ANIM SCI, V32, P201
[4]   ASSEMBLY OF INFLUENZA HEMAGGLUTININ TRIMERS AND ITS ROLE IN INTRACELLULAR-TRANSPORT [J].
COPELAND, CS ;
DOMS, RW ;
BOLZAU, EM ;
WEBSTER, RG ;
HELENIUS, A .
JOURNAL OF CELL BIOLOGY, 1986, 103 (04) :1179-1191
[5]   A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins [J].
Corti, Davide ;
Voss, Jarrod ;
Gamblin, Steven J. ;
Codoni, Giosiana ;
Macagno, Annalisa ;
Jarrossay, David ;
Vachieri, Sebastien G. ;
Pinna, Debora ;
Minola, Andrea ;
Vanzetta, Fabrizia ;
Silacci, Chiara ;
Fernandez-Rodriguez, Blanca M. ;
Agatic, Gloria ;
Bianchi, Siro ;
Giacchetto-Sasselli, Isabella ;
Calder, Lesley ;
Sallusto, Federica ;
Collins, Patrick ;
Haire, Lesley F. ;
Temperton, Nigel ;
Langedijk, Johannes P. M. ;
Skehel, John J. ;
Lanzavecchia, Antonio .
SCIENCE, 2011, 333 (6044) :850-856
[6]   A fast track influenza virus vaccine produced in insect cells [J].
Cox, Manon M. J. ;
Hashimoto, Yoshifumi .
JOURNAL OF INVERTEBRATE PATHOLOGY, 2011, 107 :S31-S41
[7]   Structure of a Classical Broadly Neutralizing Stem Antibody in Complex with a Pandemic H2 Influenza Virus Hemagglutinin [J].
Dreyfus, Cyrille ;
Ekiert, Damian C. ;
Wilson, Ian A. .
JOURNAL OF VIROLOGY, 2013, 87 (12) :7149-7154
[8]   Broadly neutralizing antibodies against influenza virus and prospects for universal therapies [J].
Ekiert, Damian C. ;
Wilson, Ian A. .
CURRENT OPINION IN VIROLOGY, 2012, 2 (02) :134-141
[9]  
Kopera E, 2014, ACTA BIOCHIM POL, V61, P597
[10]   Swine-origin pandemic H1N1 influenza virus-like particles produced in insect cells induce hemagglutination inhibiting antibodies in BALB/c mice [J].
Krammer, Florian ;
Nakowitsch, Sabine ;
Messner, Paul ;
Palmberger, Dieter ;
Ferko, Boris ;
Grabherr, Reingard .
BIOTECHNOLOGY JOURNAL, 2010, 5 (01) :17-23