The position of Spy Tag/Catcher system in hepatitis B core protein particles affects the immunogenicity and stability of the synthetic vaccine |
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| Affiliation: | 1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;4. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China;1. China Institute of Veterinary Drug Control, Beijing, PR China;2. China Animal Husbandry Industry Co., Ltd., Beijing 100070, PR China;1. Microbiology & Immunology, Gifu Pharmaceutical University, Japan;2. Kikuchi Research Center, KM Biologics Co., Ltd, Japan;1. College of Medicine, University of Florida, Gainesville, FL, USA;2. Department of Orthopaedic Surgery and Sports Medicine, University of Florida, Gainesville, FL, USA;1. Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen (THM), Wiesenstr.14, 35390 Giessen, Germany;2. Lab Essentials Applications Development, Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Goettingen, Germany;3. Institute of Technical Chemistry, Leibniz University Hannover, Callinstraße 3-9, 30167 Hannover, Lower Saxony, Germany;4. Department of Immunology, University of Tuebingen, Auf der Morgenstelle 15/3.008, 72076 Tuebingen, Germany;5. Prime Vector Technologies, Herrenberger Straße 24, 72070 Tuebingen, Germany;1. Programa Associado de Pós-Graduação em Enfermagem UPE/UEPB, Universidade de Pernambuco (UPE), Av. Agamenon Magalhães, s/n, Santo Amaro, Recife, PE 50100-010, Brazil;2. Programa de Pós-Graduação em Saúde Pública, Instituto Aggeu Magalhães, Fiocruz Pernambuco, Av. Professor Moraes Rego, s/n, Cidade Universitária, Recife, PE 50740-465, Brazil;3. Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, Keppel St, London WC1E 7HT, UK;4. Faculdade de Ciências Médicas, Universidade de Pernambuco (UPE), Tv. Jackson Pollock - Santo Amaro, Recife, PE 52171-011, Brazil;1. Travellers’ Medical Center, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan;2. Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan;3. Department of Pediatrics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan |
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| Abstract: | Presenting exogenous antigens on virus-like particles (VLPs) through “plug-and-display” decoration strategies based on SpyTag/SpyCatcher isopeptide bonding have emerged as attractive technology for vaccine synthesis. However, whether the position of ligation site in VLPs will impose effects on immunogenicity and physiochemical properties of the synthetic vaccine remains rarely investigated. Here in the present work, the well-established hepatitis B core (HBc) protein was used as chassis to construct dual-antigen influenza nanovaccines, with the conserved epitope peptides derived from extracellular domain of matrix protein M2 (M2e) and hemagglutinin (HA) as target antigens. The M2e antigen was genetically fused to the HBc in the MIR region, together with the SpyTag peptide, which was fused either in the MIR region or at the N-terminal of the protein, so that a recombinant HA antigen (rHA) linked to SpyCatcher can be displayed on it, at two different localizations. Both synthetic nanovaccines showed ability in inducing strong M2e and rHA-specific antibodies and cellular immunogenicity; nevertheless, the one in which rHA was conjugated by N-terminal Tag ligation, was superior to another one synthesized by linking the rHA to MIR region SpyTagged-HBc in all aspects, including higher antigen-specific immunogenicity responses, lower anti-HBc carrier antibody, as well as better dispersion stability. Surface charge and hydrophobicity properties of the two synthetic nanovaccines were analyzed, results revealed that linking the rHA to MIR region SpyTagged-HBc lead to more significant and disadvantageous alteration in physiochemical properties of the HBc chassis. This study will expand our knowledge on “plug-and-display” decoration strategies and provide helpful guidance for the rational design of HBc-VLPs based modular vaccines by using SpyTag/Catcher synthesis. |
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| Keywords: | HBc Virus-like particles Plug-and-display SpyTag/SpyCatcher Influenza vaccine Fusion site |
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