An envelope domain III-based chimeric antigen produced in Pichia pastoris elicits neutralizing antibodies against all four dengue virus serotypes

被引:69
作者
Etemad, Behzad [1 ]
Batra, Gaurav [1 ]
Raut, Rajendra [1 ]
Dahiya, Satinder [1 ]
Khanam, Saima [1 ]
Swaminathan, Sathyarnangalam [1 ]
Khanna, Navin [1 ]
机构
[1] Int Ctr Genet Engn & Biotechnol, RGP Grp, New Delhi 110067, India
关键词
D O I
10.4269/ajtmh.2008.79.353
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
There is currently no vaccine to prevent dengue (DEN) virus infection, which is caused by any one of four closely related serotypes, DEN-1, DEN-2, DEN-3, or DEN-4. A DEN vaccine must be tetravalent, because immunity to a single serotype does not offer cross-protection against the other serotypes. We have developed a novel tetravalent chimeric protein by fusing the receptor-binding envelope domain III (EDIII) of the four DEN virus serotypes. This protein was expressed in the yeast, Pichia pastoris, and purified to near homogeneity in high yields. Antibodies induced in mice by the tetravalent protein, formulated in different adjuvants, neutralized the infectivity of all four serotypes. This, coupled with the high expression potential of the P. pastoris system and easy one-step purification, makes the EDIII-based recombinant protein a potentially promising candidate for the development of a safe, efficacious, and inexpensive, tetravalent DEN vaccine.
引用
收藏
页码:353 / 363
页数:11
相关论文
共 63 条
[1]  
ALVAREZ M, 2005, WHO DENGUE B, V29, P49
[2]   A custom-designed recombinant multiepitope protein as a dengue diagnostic reagent [J].
AnandaRao, R ;
Swaminathan, S ;
Fernando, S ;
Jana, AM ;
Khanna, N .
PROTEIN EXPRESSION AND PURIFICATION, 2005, 41 (01) :136-147
[3]  
[Anonymous], VIROLOGY
[4]   Tetravalent neutralizing antibody response against four dengue serotypes by a single chimeric dengue envelope antigen [J].
Apt, D ;
Raviprakash, K ;
Brinkman, A ;
Semyonov, A ;
Yang, SM ;
Skinner, C ;
Diehl, L ;
Lyons, R ;
Porter, K ;
Punnonen, J .
VACCINE, 2006, 24 (03) :335-344
[5]   Biophysical characterization and vector-specific antagonist activity of domain III of the tick-borne flavivirus envelope protein [J].
Bhardwaj, S ;
Holbrook, M ;
Shope, RE ;
Barrett, ADT ;
Watowich, SJ .
JOURNAL OF VIROLOGY, 2001, 75 (08) :4002-4007
[6]   Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris [J].
Cereghino, GPL ;
Cereghino, JL ;
Ilgen, C ;
Cregg, JM .
CURRENT OPINION IN BIOTECHNOLOGY, 2002, 13 (04) :329-332
[7]   Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate [J].
Chen, YP ;
Maguire, T ;
Hileman, RE ;
Fromm, JR ;
Esko, JD ;
Linhardt, RJ ;
Marks, RM .
NATURE MEDICINE, 1997, 3 (08) :866-871
[8]   The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit virus entry [J].
Chin, J. F. L. ;
Chu, J. J. H. ;
Ng, M. L. .
MICROBES AND INFECTION, 2007, 9 (01) :1-6
[9]   ANTIBODIES AGAINST DENGUE VIRAL-PROTEINS IN PRIMARY AND SECONDARY DENGUE HEMORRHAGIC-FEVER [J].
CHURDBOONCHART, V ;
BHAMARAPRAVATI, N ;
PEAMPRAMPRECHA, S ;
SIRINAVIN, S .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1991, 44 (05) :481-493
[10]   HIGH-LEVEL EXPRESSION AND EFFICIENT ASSEMBLY OF HEPATITIS-B SURFACE-ANTIGEN IN THE METHYLOTROPHIC YEAST, PICHIA-PASTORIS [J].
CREGG, JM ;
TSCHOPP, JF ;
STILLMAN, C ;
SIEGEL, R ;
AKONG, M ;
CRAIG, WS ;
BUCKHOLZ, RG ;
MADDEN, KR ;
KELLARIS, PA ;
DAVIS, GR ;
SMILEY, BL ;
CRUZE, J ;
TORREGROSSA, R ;
VELICELEBI, G ;
THILL, GP .
BIO-TECHNOLOGY, 1987, 5 (05) :479-485