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Open AccessArticle

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

Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany
Institute of Virology, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany
Division of Experimental Clinical Research, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland
Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany
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;
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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