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Improved Innate and Adaptive Immunostimulation by Genetically Modified HIV-1 Protein Expressing NYVAC Vectors
Journal article   Open access   Peer reviewed

Improved Innate and Adaptive Immunostimulation by Genetically Modified HIV-1 Protein Expressing NYVAC Vectors

Esther D. Quakkelaar, Anke Redeker, Elias K. Haddad, Alexandre Harari, Stella Mayo McCaughey, Thomas Duhen, Abdelali Filali-Mouhim, Jean-Philippe Goulet, Nikki M. Loof, Ferry Ossendorp, …
PloS one, v 6(2), pp e16819-e16819
15 Feb 2011
DOI: https://doi.org/10.1371/journal.pone.0016819
PMID: 21347234
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0016819&type=printableView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1371/journal.pone.0016819View
Published, Version of Record (VoR) Open

Abstract

Multidisciplinary Sciences Science & Technology Science & Technology - Other Topics
Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.

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40 citations in Scopus

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Collaboration types
Industry collaboration
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
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