Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery
The delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm an...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/6/642 |
| _version_ | 1797530505749463040 |
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| author | David Peterhoff Stefanie Thalhauser Jan M. Sobczak Mona O. Mohsen Christoph Voigt Nicole Seifert Patrick Neckermann Alexandra Hauser Song Ding Quentin Sattentau Martin F. Bachmann Miriam Breunig Ralf Wagner |
| author_facet | David Peterhoff Stefanie Thalhauser Jan M. Sobczak Mona O. Mohsen Christoph Voigt Nicole Seifert Patrick Neckermann Alexandra Hauser Song Ding Quentin Sattentau Martin F. Bachmann Miriam Breunig Ralf Wagner |
| author_sort | David Peterhoff |
| collection | DOAJ |
| description | The delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm and 200 nm silica nanoparticles (SiNPs) to optimize conjugation density and attachment stability. Env was redesigned to enable site-specific cysteine-mediated covalent conjugation while maintaining its structural integrity and antigenicity. Env was anchored to different sized SiNPs with a calculated spacing of 15 nm between adjacent trimers. Both particle sizes exhibited high in vitro stability over a seven-day period. After attachment, 100 nm particles showed better colloidal stability compared to 200 nm particles. Importantly, the antigenic profile of Env was not impaired by surface attachment, indicating that the quaternary structure was maintained. In vitro Env uptake by dendritic cells was significantly enhanced when Env was delivered on the surface of nanoparticles compared to soluble Env. Furthermore, multivalent Env displayed efficiently activated B cells even at Env concentrations in the low nanomolar range. In mice, antibody responses to nanoparticle-coupled Env were stronger compared to the free protein and had equivalent effects at lower doses and without adjuvant. |
| first_indexed | 2024-03-10T10:29:56Z |
| format | Article |
| id | doaj.art-10e3fcc31e9c437b81c70b242bf689c0 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T10:29:56Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-10e3fcc31e9c437b81c70b242bf689c02023-11-21T23:42:32ZengMDPI AGVaccines2076-393X2021-06-019664210.3390/vaccines9060642Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle DeliveryDavid Peterhoff0Stefanie Thalhauser1Jan M. Sobczak2Mona O. Mohsen3Christoph Voigt4Nicole Seifert5Patrick Neckermann6Alexandra Hauser7Song Ding8Quentin Sattentau9Martin F. Bachmann10Miriam Breunig11Ralf Wagner12Institute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, GermanyInstitute of Pharmaceutical Technology, University of Regensburg, 93053 Regensburg, GermanyDepartment for BioMedical Research, University of Bern, 3010 Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, 3010 Bern, SwitzerlandInstitute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, GermanyInstitute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, GermanyInstitute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, GermanyInstitute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, GermanyEuroVacc Foundation, 1002 Lausanne, SwitzerlandSir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UKDepartment for BioMedical Research, University of Bern, 3010 Bern, SwitzerlandInstitute of Pharmaceutical Technology, University of Regensburg, 93053 Regensburg, GermanyInstitute of Medical Microbiology and Hygiene, Molecular Microbiology (Virology), University of Regensburg, 93053 Regensburg, GermanyThe delivery of HIV-1 envelope (Env) trimer-based immunogens on the surface of nanoparticles holds promise to promote immunogenicity with the aim of inducing a potent, durable and broad neutralizing antibody (bnAb) response. Towards that goal, we examined the covalent conjugation of Env to 100 nm and 200 nm silica nanoparticles (SiNPs) to optimize conjugation density and attachment stability. Env was redesigned to enable site-specific cysteine-mediated covalent conjugation while maintaining its structural integrity and antigenicity. Env was anchored to different sized SiNPs with a calculated spacing of 15 nm between adjacent trimers. Both particle sizes exhibited high in vitro stability over a seven-day period. After attachment, 100 nm particles showed better colloidal stability compared to 200 nm particles. Importantly, the antigenic profile of Env was not impaired by surface attachment, indicating that the quaternary structure was maintained. In vitro Env uptake by dendritic cells was significantly enhanced when Env was delivered on the surface of nanoparticles compared to soluble Env. Furthermore, multivalent Env displayed efficiently activated B cells even at Env concentrations in the low nanomolar range. In mice, antibody responses to nanoparticle-coupled Env were stronger compared to the free protein and had equivalent effects at lower doses and without adjuvant.https://www.mdpi.com/2076-393X/9/6/642HIV vaccinesilica nanoparticlesstabilized envelope trimerEnv |
| spellingShingle | David Peterhoff Stefanie Thalhauser Jan M. Sobczak Mona O. Mohsen Christoph Voigt Nicole Seifert Patrick Neckermann Alexandra Hauser Song Ding Quentin Sattentau Martin F. Bachmann Miriam Breunig Ralf Wagner Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery Vaccines HIV vaccine silica nanoparticles stabilized envelope trimer Env |
| title | Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery |
| title_full | Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery |
| title_fullStr | Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery |
| title_full_unstemmed | Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery |
| title_short | Augmenting the Immune Response against a Stabilized HIV-1 Clade C Envelope Trimer by Silica Nanoparticle Delivery |
| title_sort | augmenting the immune response against a stabilized hiv 1 clade c envelope trimer by silica nanoparticle delivery |
| topic | HIV vaccine silica nanoparticles stabilized envelope trimer Env |
| url | https://www.mdpi.com/2076-393X/9/6/642 |
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