Stabilized diverse HIV-1 envelope trimers for vaccine design
ABSTRACTOne of the major goals in HIV-1 vaccine development is to achieve properly folded and stabilized envelope glycoprotein (Env) trimers that mimic the native Env on the mature virion. Here, we design and characterize uncleaved prefusion-optimized (UFO) trimers for 12 Envs currently circulating...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2020.1745093 |
| _version_ | 1797265896962523136 |
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| author | Qian Wang Bingting Ma Qingtai Liang Angqi Zhu Hua Wang Lili Fu Xiaoxu Han Xuanling Shi Ye Xiang Hong Shang Linqi Zhang |
| author_facet | Qian Wang Bingting Ma Qingtai Liang Angqi Zhu Hua Wang Lili Fu Xiaoxu Han Xuanling Shi Ye Xiang Hong Shang Linqi Zhang |
| author_sort | Qian Wang |
| collection | DOAJ |
| description | ABSTRACTOne of the major goals in HIV-1 vaccine development is to achieve properly folded and stabilized envelope glycoprotein (Env) trimers that mimic the native Env on the mature virion. Here, we design and characterize uncleaved prefusion-optimized (UFO) trimers for 12 Envs currently circulating in China. Biochemical and biophysical characterization of these UFO trimers identified two subtype B/Bʹ Envs, CNE6 and MG13, which exhibited the highest trimer content and stability at a level comparable to the subtype A reference, BG505. Replacing the gp41 ectodomain (gp41ECTO) of CRF01_AE trimers with that of CNE6, MG13, and BG505 resulted in chimeric constructs with significantly improved trimer content and stability. Negative-stain electron microscopy (EM) confirmed the structural integrity of these chimeric UFO trimers with CNE6 gp41ECTO. Antibody binding assays showed that the chimeric trimers shared similar antigenic profiles to those with their original gp41ECTO domains. Our results thus revealed the intrinsic differences among HIV-1 Envs of diverse origins and the critical role of gp41ECTO in stabilizing the trimeric spike. By taking advantage of naturally stable Envs, gp41ECTO swapping may represent a universal approach for the generation of stable trimers with the desired structural and antigenic properties for downstream in vivo evaluation and vaccine development. |
| first_indexed | 2024-03-07T17:24:23Z |
| format | Article |
| id | doaj.art-c568ee4aef7e42aaac9957bb4e635227 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-25T00:52:05Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-c568ee4aef7e42aaac9957bb4e6352272024-03-11T16:04:24ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019177578610.1080/22221751.2020.1745093Stabilized diverse HIV-1 envelope trimers for vaccine designQian Wang0Bingting Ma1Qingtai Liang2Angqi Zhu3Hua Wang4Lili Fu5Xiaoxu Han6Xuanling Shi7Ye Xiang8Hong Shang9Linqi Zhang10Comprehensive AIDS Research Center and Center for Global Health and Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCenter for Global Health and Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaComprehensive AIDS Research Center and Center for Global Health and Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaComprehensive AIDS Research Center and Center for Global Health and Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaComprehensive AIDS Research Center and Center for Global Health and Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaComprehensive AIDS Research Center and Center for Global Health and Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaKey Laboratory of AIDS Immunology of the Ministry of Health, Department of Laboratory Medicine, No. 1 Hospital of China Medical University, Shenyang, People’s Republic of ChinaComprehensive AIDS Research Center and Center for Global Health and Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaCenter for Global Health and Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaKey Laboratory of AIDS Immunology of the Ministry of Health, Department of Laboratory Medicine, No. 1 Hospital of China Medical University, Shenyang, People’s Republic of ChinaComprehensive AIDS Research Center and Center for Global Health and Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, People’s Republic of ChinaABSTRACTOne of the major goals in HIV-1 vaccine development is to achieve properly folded and stabilized envelope glycoprotein (Env) trimers that mimic the native Env on the mature virion. Here, we design and characterize uncleaved prefusion-optimized (UFO) trimers for 12 Envs currently circulating in China. Biochemical and biophysical characterization of these UFO trimers identified two subtype B/Bʹ Envs, CNE6 and MG13, which exhibited the highest trimer content and stability at a level comparable to the subtype A reference, BG505. Replacing the gp41 ectodomain (gp41ECTO) of CRF01_AE trimers with that of CNE6, MG13, and BG505 resulted in chimeric constructs with significantly improved trimer content and stability. Negative-stain electron microscopy (EM) confirmed the structural integrity of these chimeric UFO trimers with CNE6 gp41ECTO. Antibody binding assays showed that the chimeric trimers shared similar antigenic profiles to those with their original gp41ECTO domains. Our results thus revealed the intrinsic differences among HIV-1 Envs of diverse origins and the critical role of gp41ECTO in stabilizing the trimeric spike. By taking advantage of naturally stable Envs, gp41ECTO swapping may represent a universal approach for the generation of stable trimers with the desired structural and antigenic properties for downstream in vivo evaluation and vaccine development.https://www.tandfonline.com/doi/10.1080/22221751.2020.1745093HIV-1 Envsubtype CRF01_AEuncleaved prefusion-optimized (UFO) trimerSOSIP trimervaccine design |
| spellingShingle | Qian Wang Bingting Ma Qingtai Liang Angqi Zhu Hua Wang Lili Fu Xiaoxu Han Xuanling Shi Ye Xiang Hong Shang Linqi Zhang Stabilized diverse HIV-1 envelope trimers for vaccine design Emerging Microbes and Infections HIV-1 Env subtype CRF01_AE uncleaved prefusion-optimized (UFO) trimer SOSIP trimer vaccine design |
| title | Stabilized diverse HIV-1 envelope trimers for vaccine design |
| title_full | Stabilized diverse HIV-1 envelope trimers for vaccine design |
| title_fullStr | Stabilized diverse HIV-1 envelope trimers for vaccine design |
| title_full_unstemmed | Stabilized diverse HIV-1 envelope trimers for vaccine design |
| title_short | Stabilized diverse HIV-1 envelope trimers for vaccine design |
| title_sort | stabilized diverse hiv 1 envelope trimers for vaccine design |
| topic | HIV-1 Env subtype CRF01_AE uncleaved prefusion-optimized (UFO) trimer SOSIP trimer vaccine design |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2020.1745093 |
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