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Virus-like particles derived from Pichia pastoris-expressed dengue virus type 1 glycoprotein elicit homotypic virus-neutralizing envelope domain III-directed antibodies

Overview of attention for article published in BMC Biotechnology, June 2016
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2 tweeters

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23 Dimensions

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58 Mendeley
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Title
Virus-like particles derived from Pichia pastoris-expressed dengue virus type 1 glycoprotein elicit homotypic virus-neutralizing envelope domain III-directed antibodies
Published in
BMC Biotechnology, June 2016
DOI 10.1186/s12896-016-0280-y
Pubmed ID
Authors

Ankur Poddar, Viswanathan Ramasamy, Rahul Shukla, Ravi Kant Rajpoot, Upasana Arora, Swatantra K. Jain, Sathyamangalam Swaminathan, Navin Khanna

Abstract

Four antigenically distinct serotypes (1-4) of dengue viruses (DENVs) cause dengue disease. Antibodies to any one DENV serotype have the potential to predispose an individual to more severe disease upon infection with a different DENV serotype. A dengue vaccine must elicit homotypic neutralizing antibodies to all four DENV serotypes to avoid the risk of such antibody-dependent enhancement in the vaccine recipient. This is a formidable challenge as evident from the lack of protective efficacy against DENV-2 by a tetravalent live attenuated dengue vaccine that has completed phase III trials recently. These trial data underscore the need to explore non-replicating subunit vaccine alternatives. Recently, using the methylotrophic yeast Pichia pastoris, we showed that DENV-2 and DENV-3 envelope (E) glycoproteins, expressed in absence of prM, implicated in causing severe dengue disease, self-assemble into virus-like particles (VLPs), which elicit predominantly virus-neutralizing antibodies and confer significant protection against lethal DENV challenge in an animal model. The current study extends this work to a third DENV serotype. We cloned and expressed DENV-1 E antigen in P. pastoris, and purified it to near homogeneity. Recombinant DENV-1 E underwent post-translational processing, namely, signal peptide cleavage and glycosylation. Purified DENV-1 E self-assembled into stable VLPs, based on electron microscopy and dynamic light scattering analysis. Epitope mapping with monoclonal antibodies revealed that the VLPs retained the overall antigenic integrity of the virion particles despite the absence of prM. Subtle changes accompanied the efficient display of E domain III (EDIII), which contains type-specific neutralizing epitopes. These VLPs were immunogenic, eliciting predominantly homotypic EDIII-directed DENV-1-specific neutralizing antibodies. This work demonstrates the inherent potential of P. pastoris-expressed DENV-1 E glycoprotein to self-assemble into VLPs eliciting predominantly homotypic neutralizing antibodies. This work justifies an investigation of the last remaining serotype, namely, DENV-4, to assess if it also shares the desirable vaccine potential manifested by the remaining three DENV serotypes. Such efforts could make it possible to envisage the development of a tetravalent dengue vaccine based on VLPs of P. pastoris-expressed E glycoproteins of the four DENV serotypes.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 58 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Unknown 57 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 19%
Student > Master 8 14%
Student > Ph. D. Student 8 14%
Student > Doctoral Student 5 9%
Professor 5 9%
Other 9 16%
Unknown 12 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 26%
Immunology and Microbiology 10 17%
Agricultural and Biological Sciences 8 14%
Business, Management and Accounting 2 3%
Chemical Engineering 2 3%
Other 7 12%
Unknown 14 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 June 2016.
All research outputs
#5,714,508
of 7,907,411 outputs
Outputs from BMC Biotechnology
#337
of 471 outputs
Outputs of similar age
#171,805
of 267,827 outputs
Outputs of similar age from BMC Biotechnology
#12
of 19 outputs
Altmetric has tracked 7,907,411 research outputs across all sources so far. This one is in the 24th percentile – i.e., 24% of other outputs scored the same or lower than it.
So far Altmetric has tracked 471 research outputs from this source. They receive a mean Attention Score of 4.6. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,827 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.