Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens
Major neutralizing antibody immune evasion strategies of the HIV-1 envelope glycoprotein (Env) trimer include conformational and structural instability. Stabilized soluble trimers such as BG505 SOSIP.664 mimic the structure of virion-associated Env but nevertheless sample different conformational st...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Microbiology
2015
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| _version_ | 1826311018149576704 |
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| author | Schiffner, T de Val, N Russell, RA de Taeye, SW de la Peña, AT Ozorowski, G Kim, HJ Nieusma, T Brod, F Cupo, A Sanders, RW Moore, JP Ward, AB Sattentau, QJ |
| author_facet | Schiffner, T de Val, N Russell, RA de Taeye, SW de la Peña, AT Ozorowski, G Kim, HJ Nieusma, T Brod, F Cupo, A Sanders, RW Moore, JP Ward, AB Sattentau, QJ |
| author_sort | Schiffner, T |
| collection | OXFORD |
| description | Major neutralizing antibody immune evasion strategies of the HIV-1 envelope glycoprotein (Env) trimer include conformational and structural instability. Stabilized soluble trimers such as BG505 SOSIP.664 mimic the structure of virion-associated Env but nevertheless sample different conformational states. Here we demonstrate that treating BG505 SOSIP.664 trimers with glutaraldehyde or a heterobifunctional cross-linker introduces additional stability with relatively modest effects on antigenicity. Thus, most broadly neutralizing antibody (bNAb) epitopes were preserved after cross-linking, whereas the binding of most weakly or nonneutralizing antibodies (non-NAb) was reduced. Cross-linking stabilized all Env conformers present within a mixed population, and individual conformers could be isolated by bNAb affinity chromatography. Both positive selection of cross-linked conformers using the quaternary epitope-specific bNAbs PGT145, PGT151, and 3BC315 and negative selection with non-NAbs against the V3 region enriched for trimer populations with improved antigenicity for bNAbs. Similar results were obtained using the clade B B41 SOSIP.664 trimer. The cross-linking method may, therefore, be useful for countering the natural conformational heterogeneity of some HIV-1 Env proteins and, by extrapolation, also vaccine immunogens from other pathogens. |
| first_indexed | 2024-03-07T08:02:11Z |
| format | Journal article |
| id | oxford-uuid:7b30fe5e-2d20-4bbf-8542-76ebc598bb45 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:02:11Z |
| publishDate | 2015 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:7b30fe5e-2d20-4bbf-8542-76ebc598bb452023-10-10T10:03:55ZChemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigensJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7b30fe5e-2d20-4bbf-8542-76ebc598bb45EnglishSymplectic Elements at OxfordAmerican Society for Microbiology2015Schiffner, Tde Val, NRussell, RAde Taeye, SWde la Peña, ATOzorowski, GKim, HJNieusma, TBrod, FCupo, ASanders, RWMoore, JPWard, ABSattentau, QJMajor neutralizing antibody immune evasion strategies of the HIV-1 envelope glycoprotein (Env) trimer include conformational and structural instability. Stabilized soluble trimers such as BG505 SOSIP.664 mimic the structure of virion-associated Env but nevertheless sample different conformational states. Here we demonstrate that treating BG505 SOSIP.664 trimers with glutaraldehyde or a heterobifunctional cross-linker introduces additional stability with relatively modest effects on antigenicity. Thus, most broadly neutralizing antibody (bNAb) epitopes were preserved after cross-linking, whereas the binding of most weakly or nonneutralizing antibodies (non-NAb) was reduced. Cross-linking stabilized all Env conformers present within a mixed population, and individual conformers could be isolated by bNAb affinity chromatography. Both positive selection of cross-linked conformers using the quaternary epitope-specific bNAbs PGT145, PGT151, and 3BC315 and negative selection with non-NAbs against the V3 region enriched for trimer populations with improved antigenicity for bNAbs. Similar results were obtained using the clade B B41 SOSIP.664 trimer. The cross-linking method may, therefore, be useful for countering the natural conformational heterogeneity of some HIV-1 Env proteins and, by extrapolation, also vaccine immunogens from other pathogens. |
| spellingShingle | Schiffner, T de Val, N Russell, RA de Taeye, SW de la Peña, AT Ozorowski, G Kim, HJ Nieusma, T Brod, F Cupo, A Sanders, RW Moore, JP Ward, AB Sattentau, QJ Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens |
| title | Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens |
| title_full | Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens |
| title_fullStr | Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens |
| title_full_unstemmed | Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens |
| title_short | Chemical cross-linking stabilizes native-like HIV-1 envelope glycoprotein trimer antigens |
| title_sort | chemical cross linking stabilizes native like hiv 1 envelope glycoprotein trimer antigens |
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