%0 Journal Article
%T Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines
%A Cornelia Barnowski
%A Dominik Damm
%A Huimin Yan
%A Nicole Kadzioch
%A Vladimir Temchura
%J Archive of "Pharmaceutics".
%D 2019
%R 10.3390/pharmaceutics11050204
%X 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. ˇ°Wild-typeˇ± 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
%K nano-vaccines
%K HIV-based VLP
%K flagellin
%K B-cell targeting
%K adjuvant
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572692/