Barnowski C, Kadzioch N, Damm D, Yan H, Temchura V (2019)
Publication Type: Journal article
Publication year: 2019
Book Volume: 11
Article Number: 204
Journal Issue: 5
DOI: 10.3390/pharmaceutics11050204
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.
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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