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A heterogeneous human immunodeficiency virus-like particle (VLP) formulation produced by a novel vector system.

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Title: A heterogeneous human immunodeficiency virus-like particle (VLP) formulation produced by a novel vector system.
Authors: Pankrac, J
Klein, K
McKay, PF
King, DFL
Bain, K
Knapp, J
Biru, T
Wijewardhana, CN
Pawa, R
Canaday, DH
Gao, Y
Fidler, S
Shattock, RJ
Arts, EJ
Mann, JFS
Item Type: Journal Article
Abstract: First identified as the etiological agent behind Acquired Immunodeficiency Syndrome (AIDS) in the early 1980s, HIV-1 has continued to spread into a global pandemic and major public health concern. Despite the success of antiretroviral therapy at reducing HIV-1 viremia and preventing the dramatic CD4+ T-cell collapse, infected individuals remain HIV positive for life. Unfortunately, it is increasingly clear that natural immunity is not, and may never be, protective against this pathogen. Therefore, efficacious vaccine interventions, which can either prevent infection or eradicate the latent viral reservoir and effect cure, are a major medical priority. Here we describe the development of a safe vaccine platform, currently being utilized in on-going prophylactic and therapeutic preclinical studies and consisting of highly heterogeneous virus-like particle formulations that represent the virus diversity within infected individuals. These VLPs contain no 5'LTR, no functional integrase, and have a severely mutated stem loop 1-thereby preventing any potential reverse transcription, integration, and RNA packaging. Furthermore, we demonstrate that these VLPs are morphologically identical to wild-type virus with polyvalent Env in a functional form. Finally, we show that the VLPs are antigenic and capable of generating strong immune recall responses.
Issue Date: 19-Jan-2018
Date of Acceptance: 8-Dec-2017
URI: http://hdl.handle.net/10044/1/56550
DOI: https://dx.doi.org/10.1038/s41541-017-0040-6
ISSN: 2059-0105
Publisher: Nature Publishing Group
Journal / Book Title: npj Vaccines
Volume: 3
Copyright Statement: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. © The Author(s) 2018
Publication Status: Published online
Article Number: 2
Appears in Collections:Department of Medicine
Faculty of Medicine



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