Engineered Ferritin Nanoparticle Vaccines Enable Rapid Screening of Antibody Functionalization to Boost Immune Responses.

Autor: Vu MN; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, 3010, Australia.; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, VIC, 3052, Australia.; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.; Faculty of Pharmaceutics and Pharmaceutical Technology, Hanoi University of Pharmacy, 10000, Hanoi, Vietnam., Pilkington EH; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, 3010, Australia.; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, VIC, 3052, Australia.; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia., Lee WS; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, 3010, Australia., Tan HX; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, 3010, Australia.; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, VIC, 3052, Australia., Davis TP; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, VIC, 3052, Australia.; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.; Australia Institute of Bioengineering & Nanotechnology, University of Queensland, Brisbane, QLD, 4072, Australia., Truong NP; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, VIC, 3052, Australia.; Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia., Kent SJ; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, 3010, Australia.; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, VIC, 3052, Australia.; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, 3004, Australia., Wheatley AK; Peter Doherty Institute for Infection and Immunity, Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC, 3010, Australia.; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, VIC, 3052, Australia.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2023 Jul; Vol. 12 (17), pp. e2202595. Date of Electronic Publication: 2023 Feb 24.
DOI: 10.1002/adhm.202202595
Abstrakt: Employing monoclonal antibodies to target vaccine antigens to different immune cells within lymph nodes where adaptive immunity is initiated can provide a mechanism to fine-tune the magnitude or the quality of immune responses. However, studying the effects of different targeting antibodies head-to-head is challenging due to the lack of a feasible method that allows rapid screening of multiple antibodies for their impact on immunogenicity. Here self-assembling ferritin nanoparticles are prepared that co-display vaccine antigens and the Fc-binding domain of Staphylococcal protein A, allowing rapid attachment of soluble antibodies to the nanoparticle surface. Using this tunable system, ten antibodies targeting different immune cell subsets are screened, with targeting to Clec9a associated with higher serum antibody titers after immunization. Immune cell targeting using ferritin nanoparticles with anti-Clec9a antibodies drives concentrated deposition of antigens within germinal centers, boosting germinal center formation and robust antibody responses. However, the capacity to augment humoral immunity is antigen-dependent, with significant boosting observed for prototypic ovalbumin immunogens but reduced effectiveness with the SARS-CoV-2 RBD. This work provides a rapid platform for screening targeting antibodies, which will accelerate mechanistic insights into optimal delivery strategies for nanoparticle-based vaccines to maximize protective immunity.
(© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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