Multifunctional calcium phosphate nanoparticles as novel HIV-1 vaccine platform
Final Report Abstract
During the past decade, antigen-functionalized nanoparticles have become a major focus in the field of experimental human immunodeficiency virus 1 (HIV-1) vaccines. This project investigated strategies to increase the efficacy of HIV-1 nanoparticle vaccines by optimizing the induction of antibody responses. To achieve this, we proposed two novel HIV-1 vaccination strategies, both based on biodegradable inorganic calcium phosphate (CaP) nanoparticles (NPs). These NPs offer several advantages compared to biological and polymer-based NPs and provide a customizable vaccination platform. The first strategy required two NP components: one to induce optimized T helper cell responses (T-CaP), while the other presents the viral HIV-1 envelope glycoprotein (Env) to B cells (B-CaP). For the second vaccination strategy, we aimed to use Env-conjugated NPs containing L1 capsid protein of human papilloma virus (HPV). Within the project, we designed and synthesized T-CaP NPs specifically to induce T helper cells. These NPs demonstrated enhanced targeting to dendritic cells and expansion of antigenspecific T helper cells. To attach Env trimers to the surface of NPs, we developed a highly selective bio-conjugation method. This method effectively maintains the native-like protein conformation of Env and has broad potential application in functionalizing nanoparticles with stabilized viral antigens. CaP NPs bio-conjugated with Env (B-CaPs) showed increased efficiency in activating Env-specific B cells and inducing Env-specific antibody responses in animal vaccination experiments. We also optimized the production of L1 HPV particles and encapsulated them within a silica shell (L1-Si). Using the established bio-conjugation, we attached Env to the surface of these NPs (L1-Si-Env). In vitro L1-Si-Env efficiently activated Env-specific B cells. In vivo L1-Si-Env NPs improved antibody responses against Env without the need for an adjuvant. Thus, these optimized T-CaPs, B-CaPs, and L1-Si-Env NPs warrant further in-depth exploration as potential HIV-1 vaccines.
Publications
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Covalent coupling of HIV-1 glycoprotein trimers to biodegradable calcium phosphate nanoparticles via genetically encoded aldehyde-tags. Acta Biomaterialia, 140, 586-600.
Damm, D.; Kostka, K.; Weingärtner, C.; Wagner, J.T.; Rojas-Sánchez, L.; Gensberger-Reigl, S.; Sokolova, V.; Überla, K.; Epple, M. & Temchura, V.
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Oberflächenmodifizierung von Calciumphosphat-Nanopartikeln Mittels Klick-Chemie. University of Duisburg Essen; 2023
Kostka K.
