التفاصيل البيبلوغرافية
| العنوان: |
HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients |
| المؤلفون: |
Files, J.K., Sterrett, S., Henostroza, S., Fucile, C., Maroney, K., Fram, T., Mallal, S., Kalams, S., Carlson, J., Rosenberg, A., Erdmann, N., Bansal, A., Goepfert, P.A., Silvestri, G. |
| المصدر: |
Files, J.K., Sterrett, S., Henostroza, S., Fucile, C., Maroney, K., Fram, T., Mallal, S. , Kalams, S., Carlson, J., Rosenberg, A., Erdmann, N., Bansal, A., Goepfert, P.A. and Silvestri, G. (2022) HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients. Journal of Virology, 96 (17). |
| بيانات النشر: |
American Society for Microbiology |
| سنة النشر: |
2022 |
| المجموعة: |
Murdoch University: Murdoch Research Repository |
| الوصف: |
Epitopes with evidence of HLA-II-associated adaptation induce poorly immunogenic CD4+ T-cell responses in HIV-positive (HIV+) individuals. Many such escaped CD4+ T-cell epitopes are encoded by HIV-1 vaccines being evaluated in clinical trials. Here, we assessed whether this viral adaptation adversely impacts CD4+ T-cell responses following HIV-1 vaccination, thereby representing escaped epitopes. When evaluated in separate peptide pools, vaccine-encoded adapted epitopes (AE) induced CD4+ T-cell responses less frequently than nonadapted epitopes (NAE). We also demonstrated that in a polyvalent vaccine, where both forms of the same epitope were encoded, AE were less immunogenic. NAE-specific CD4+ T cells had increased, albeit low, levels of interferon gamma (IFN-γ) cytokine production. Single-cell transcriptomic analyses showed that NAE-specific CD4+ T cells expressed interferon-related genes, while AE-specific CD4+ T cells resembled a Th2 phenotype. Importantly, the magnitude of NAE-specific CD4+ T-cell responses, but not that of AE-specific responses, was found to positively correlate with Env-specific antibodies in a vaccine efficacy trial. Together, these findings show that HLA-II-associated viral adaptation reduces CD4+ T-cell responses in HIV-1 vaccine recipients and suggest that vaccines encoding a significant number of AE may not provide optimal B-cell help for HIV-specific antibody production. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
https://researchrepository.murdoch.edu.au/id/eprint/65934/; full_text_status:none |
| الاتاحة: |
https://researchrepository.murdoch.edu.au/id/eprint/65934/ |
| Rights: |
© 2022 American Society for Microbiology |
| رقم الانضمام: |
edsbas.DC400D3 |
| قاعدة البيانات: |
BASE |