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Open AccessArticle

Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines

1
Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany
2
Institute of Virology, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany
3
Division of Experimental Clinical Research, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
4
Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
5
Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(5), 204; https://doi.org/10.3390/pharmaceutics11050204
Received: 19 March 2019 / Revised: 24 April 2019 / Accepted: 26 April 2019 / Published: 1 May 2019
(This article belongs to the Special Issue Nanoparticles to Improve the Efficacy of Vaccines)
The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is a potent inducer of innate immunity and it has demonstrated adjuvant effectiveness due to its affinity for toll-like receptor 5 (TLR5). In contrast to most TLR ligands, flagellin is a protein and can induce an immune response against itself. To avoid side-effects, we incorporated a less inflammatory and less immunogenic form of flagellin as an adjuvant into HIV-based nanoparticle B-cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). While flagellin significantly enhanced HEL-specific IgG responses, anti-Env antibody responses were suppressed. We demonstrated that flagellin did not activate B-cells directly in vitro, but might compete for CD4+ T-cell help in vivo. Therefore, we hypothesize that in the context of VLP-based B-cell nano-vaccines, flagellin serves as an antigen itself and may outcompete a less immunogenic antigen with its antibody response. In contrast, in combination with a strong immunogen, the adjuvant activity of flagellin may dominate over its immunogenicity. View Full-Text
Keywords: nano-vaccines; HIV-based VLP; flagellin; B-cell targeting; adjuvant nano-vaccines; HIV-based VLP; flagellin; B-cell targeting; adjuvant
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MDPI and ACS Style

Barnowski, C.; Kadzioch, N.; Damm, D.; Yan, H.; Temchura, V. Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines. Pharmaceutics 2019, 11, 204.

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