Advantages and limitations of integrated flagellin adjuvants for HIV-based nanoparticle B-cell vaccines

Barnowski C, Kadzioch N, Damm D, Yan H, Temchura V (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Pharmaceutics MDPI

Book Volume: 11

Article Number: 204

Journal Issue: 5

DOI: 10.3390/pharmaceutics11050204

Abstract

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.

Authors with CRIS profile

Dominik Damm Institute of Clinical and Molecular Virology Vladimir Temchura Institute of Clinical and Molecular Virology

Involved external institutions

Ruhr-Universität Bochum (RUB) DE Germany (DE) Wuhan Institute Of Virology / 中国科学院武汉病毒研究所 CN China (CN)

How to cite

APA:

Barnowski, C., Kadzioch, N., Damm, D., Yan, H., & Temchura, V. (2019). Advantages and limitations of integrated flagellin adjuvants for HIV-based nanoparticle B-cell vaccines. Pharmaceutics, 11(5). https://doi.org/10.3390/pharmaceutics11050204

MLA:

Barnowski, Cornelia, et al. "Advantages and limitations of integrated flagellin adjuvants for HIV-based nanoparticle B-cell vaccines." Pharmaceutics 11.5 (2019).

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