The impact of size on particle drainage dynamics and antibody response
<p dir="ltr">Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interac...
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2021
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| _version_ | 1864513550825816064 |
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| author | Simon Zinkhan (14214245) |
| author2 | Anete Ogrina (14829949) Ina Balke (14829952) Gunta Reseviča (16932516) Andris Zeltins (6641210) Simone de Brot (15317944) Cyrill Lipp (6641207) Xinyue Chang (9279155) Lisha Zha (4056970) Monique Vogel (405685) Martin F. Bachmann (7116422) Mona O. Mohsen (4056964) |
| author2_role | author author author author author author author author author author author |
| author_facet | Simon Zinkhan (14214245) Anete Ogrina (14829949) Ina Balke (14829952) Gunta Reseviča (16932516) Andris Zeltins (6641210) Simone de Brot (15317944) Cyrill Lipp (6641207) Xinyue Chang (9279155) Lisha Zha (4056970) Monique Vogel (405685) Martin F. Bachmann (7116422) Mona O. Mohsen (4056964) |
| author_role | author |
| dc.creator.none.fl_str_mv | Simon Zinkhan (14214245) Anete Ogrina (14829949) Ina Balke (14829952) Gunta Reseviča (16932516) Andris Zeltins (6641210) Simone de Brot (15317944) Cyrill Lipp (6641207) Xinyue Chang (9279155) Lisha Zha (4056970) Monique Vogel (405685) Martin F. Bachmann (7116422) Mona O. Mohsen (4056964) |
| dc.date.none.fl_str_mv | 2021-03-10T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.jconrel.2021.01.012 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_impact_of_size_on_particle_drainage_dynamics_and_antibody_response/24083676 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Medical microbiology Virus-like particles Cowpea chlorotic mottle virus Humoral immune response |
| dc.title.none.fl_str_mv | The impact of size on particle drainage dynamics and antibody response |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interaction with and activation of B cells and innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T = 3 icosahedral particles. (T) is the triangulation number that refers to the number and arrangements of the subunits (pentamers and hexamers) of the VLPs. CCMV-VLPs can be easily expressed in an E. coli host system and package ssRNA during the expression process. Recently, we have engineered CCMV-VLPs by incorporating the universal tetanus toxin (TT) epitope at the N-terminus. The modified CCMVTT-VLPs successfully form icosahedral particles T = 3, with a diameter of ~30 nm analogous to the parental VLPs. Interestingly, incorporating TT epitope at the C-terminus of CCMVTT-VLPs results in the formation of Rod-shaped VLPs, ~1 μm in length and ~ 30 nm in width. In this study, we have investigated the draining kinetics and immunogenicity of both engineered forms (termed as Round-shaped CCMVTT-VLPs and Rod-shaped CCMVTTVLPs) as potential B cell immunogens using different in vitro and in vivo assays. Our results reveal that Roundshaped CCMVTT-VLPs are more efficient in draining to secondary lymphoid organs to charge professional antigen-presenting cells as well as B cells. Furthermore, compared to Rod-shaped CCMVTT-VLPs, Round-shaped CCMVTT-VLPs led to more than 100-fold increased systemic IgG and IgA responses accompanied by prominent formation of splenic germinal centers. Round-shaped CCMVTT-VLPs could also polarize the induced T cell response toward Th1. To our knowledge, this is the first study investigating and comparing the draining kinetics and immunogenicity of one and the same VLP monomer forming nano-sized icosahedra or rods in the micrometer size.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Controlled Release<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jconrel.2021.01.012" target="_blank">https://dx.doi.org/10.1016/j.jconrel.2021.01.012</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_5de4bd6693b9c4f0099c853c9a64f1e5 |
| identifier_str_mv | 10.1016/j.jconrel.2021.01.012 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24083676 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The impact of size on particle drainage dynamics and antibody responseSimon Zinkhan (14214245)Anete Ogrina (14829949)Ina Balke (14829952)Gunta Reseviča (16932516)Andris Zeltins (6641210)Simone de Brot (15317944)Cyrill Lipp (6641207)Xinyue Chang (9279155)Lisha Zha (4056970)Monique Vogel (405685)Martin F. Bachmann (7116422)Mona O. Mohsen (4056964)Biomedical and clinical sciencesImmunologyMedical microbiologyVirus-like particlesCowpea chlorotic mottle virusHumoral immune response<p dir="ltr">Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interaction with and activation of B cells and innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T = 3 icosahedral particles. (T) is the triangulation number that refers to the number and arrangements of the subunits (pentamers and hexamers) of the VLPs. CCMV-VLPs can be easily expressed in an E. coli host system and package ssRNA during the expression process. Recently, we have engineered CCMV-VLPs by incorporating the universal tetanus toxin (TT) epitope at the N-terminus. The modified CCMVTT-VLPs successfully form icosahedral particles T = 3, with a diameter of ~30 nm analogous to the parental VLPs. Interestingly, incorporating TT epitope at the C-terminus of CCMVTT-VLPs results in the formation of Rod-shaped VLPs, ~1 μm in length and ~ 30 nm in width. In this study, we have investigated the draining kinetics and immunogenicity of both engineered forms (termed as Round-shaped CCMVTT-VLPs and Rod-shaped CCMVTTVLPs) as potential B cell immunogens using different in vitro and in vivo assays. Our results reveal that Roundshaped CCMVTT-VLPs are more efficient in draining to secondary lymphoid organs to charge professional antigen-presenting cells as well as B cells. Furthermore, compared to Rod-shaped CCMVTT-VLPs, Round-shaped CCMVTT-VLPs led to more than 100-fold increased systemic IgG and IgA responses accompanied by prominent formation of splenic germinal centers. Round-shaped CCMVTT-VLPs could also polarize the induced T cell response toward Th1. To our knowledge, this is the first study investigating and comparing the draining kinetics and immunogenicity of one and the same VLP monomer forming nano-sized icosahedra or rods in the micrometer size.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Controlled Release<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.jconrel.2021.01.012" target="_blank">https://dx.doi.org/10.1016/j.jconrel.2021.01.012</a></p>2021-03-10T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.jconrel.2021.01.012https://figshare.com/articles/journal_contribution/The_impact_of_size_on_particle_drainage_dynamics_and_antibody_response/24083676CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/240836762021-03-10T00:00:00Z |
| spellingShingle | The impact of size on particle drainage dynamics and antibody response Simon Zinkhan (14214245) Biomedical and clinical sciences Immunology Medical microbiology Virus-like particles Cowpea chlorotic mottle virus Humoral immune response |
| status_str | publishedVersion |
| title | The impact of size on particle drainage dynamics and antibody response |
| title_full | The impact of size on particle drainage dynamics and antibody response |
| title_fullStr | The impact of size on particle drainage dynamics and antibody response |
| title_full_unstemmed | The impact of size on particle drainage dynamics and antibody response |
| title_short | The impact of size on particle drainage dynamics and antibody response |
| title_sort | The impact of size on particle drainage dynamics and antibody response |
| topic | Biomedical and clinical sciences Immunology Medical microbiology Virus-like particles Cowpea chlorotic mottle virus Humoral immune response |