Recombinant Dengue Virus 4 Envelope Glycoprotein Virus-Like Particles Derived from Pichia pastoris Are Capable of Eliciting Homotypic Domain III-Directed Neutralizing Antibodies

被引:22
|
作者
Khetarpal, Niyati [1 ]
Shukla, Rahul [1 ]
Rajpoot, Ravi Kant [1 ]
Poddar, Ankur [1 ]
Pal, Meena [1 ]
Swaminathan, Sathyamangalam [2 ]
Arora, Upasana [1 ]
Khanna, Navin [1 ]
机构
[1] Int Ctr Genet Engn & Biotechnol, Recombinant Gene Prod Grp, Aruna Asaf Ali Marg, New Delhi 110067, India
[2] Birla Inst Technol & Sci, Dept Biol Sci, Hyderabad, Andhra Pradesh, India
来源
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE | 2017年 / 96卷 / 01期
关键词
MONOCLONAL-ANTIBODIES; VACCINES; INFECTION; EFFICACY;
D O I
10.4269/ajtmh.16-0503
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Dengue is a viral pandemic caused by four dengue virus serotypes (DENV-1, 2, 3, and 4) transmitted by Aedes mosquitoes. Reportedly, there has been a 2-fold increase in dengue cases every decade. An efficacious tetravalent vaccine, which can provide long-term immunity against all four serotypes in all target populations, is still unavailable. Despite the progress being made in the live virus-based dengue vaccines, the World Health Organization strongly recommends the development of alternative approaches for safe, affordable, and efficacious dengue vaccine candidates. We have explored virus-like particles (VLPs)-based nonreplicating subunit vaccine approach and have developed recombinant envelope ectodomains of DENV-1, 2, and 3 expressed in Pichia pastoris. These self-assembled into VLPs without pre-membrane (prM) protein, which limits the generation of enhancing antibodies, and elicited type specific neutralizing antibodies against the respective serotype. Encouraged by these results, we have extended this work further by developing P. pastoris expressed DENV-4 ectodomain (DENV-4 E) in this study, which was found to be glycosylated and assembled into spherical VLPs without prM, and displayed critical neutralizing epitopes on its surface. These VLPs were found to be immunogenic in mice and elicited DENV-4-specific neutralizing antibodies, which were predominantly directed against envelope domain III, implicated in host-receptor recognition and virus entry. These observations underscore the potential of VLP-based nonreplicative vaccine approach as a means to develop a safe, efficacious, and tetravalent dengue subunit vaccine. This work paves the way for the evaluation of a DENV E-based tetravalent dengue vaccine candidate, as an alternative to live virus-based dengue vaccines.
引用
收藏
页码:126 / 134
页数:9
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