Definition of the viral targets of protective HIV-1-specific T cell responses.
BACKGROUND: The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating exp...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1826291964811673600 |
|---|---|
| author | Mothe, B Llano, A Ibarrondo, J Daniels, M Miranda, C Zamarreño, J Bach, V Zuniga, R Pérez-Álvarez, S Berger, C Puertas, M Martinez-Picado, J Rolland, M Farfan, M Szinger, J Hildebrand, W Yang, O Sanchez-Merino, V Brumme, C Brumme, Z Heckerman, D Allen, T Mullins, J Gómez, G Goulder, P |
| author_facet | Mothe, B Llano, A Ibarrondo, J Daniels, M Miranda, C Zamarreño, J Bach, V Zuniga, R Pérez-Álvarez, S Berger, C Puertas, M Martinez-Picado, J Rolland, M Farfan, M Szinger, J Hildebrand, W Yang, O Sanchez-Merino, V Brumme, C Brumme, Z Heckerman, D Allen, T Mullins, J Gómez, G Goulder, P |
| author_sort | Mothe, B |
| collection | OXFORD |
| description | BACKGROUND: The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. METHODS: Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. RESULTS: For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes. CONCLUSIONS: The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections. |
| first_indexed | 2024-03-07T03:07:25Z |
| format | Journal article |
| id | oxford-uuid:b30373bd-bdbf-43c1-8666-4fc5d4088293 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:07:25Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:b30373bd-bdbf-43c1-8666-4fc5d40882932022-03-27T04:16:02ZDefinition of the viral targets of protective HIV-1-specific T cell responses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b30373bd-bdbf-43c1-8666-4fc5d4088293EnglishSymplectic Elements at Oxford2011Mothe, BLlano, AIbarrondo, JDaniels, MMiranda, CZamarreño, JBach, VZuniga, RPérez-Álvarez, SBerger, CPuertas, MMartinez-Picado, JRolland, MFarfan, MSzinger, JHildebrand, WYang, OSanchez-Merino, VBrumme, CBrumme, ZHeckerman, DAllen, TMullins, JGómez, GGoulder, PBACKGROUND: The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. METHODS: Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. RESULTS: For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes. CONCLUSIONS: The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections. |
| spellingShingle | Mothe, B Llano, A Ibarrondo, J Daniels, M Miranda, C Zamarreño, J Bach, V Zuniga, R Pérez-Álvarez, S Berger, C Puertas, M Martinez-Picado, J Rolland, M Farfan, M Szinger, J Hildebrand, W Yang, O Sanchez-Merino, V Brumme, C Brumme, Z Heckerman, D Allen, T Mullins, J Gómez, G Goulder, P Definition of the viral targets of protective HIV-1-specific T cell responses. |
| title | Definition of the viral targets of protective HIV-1-specific T cell responses. |
| title_full | Definition of the viral targets of protective HIV-1-specific T cell responses. |
| title_fullStr | Definition of the viral targets of protective HIV-1-specific T cell responses. |
| title_full_unstemmed | Definition of the viral targets of protective HIV-1-specific T cell responses. |
| title_short | Definition of the viral targets of protective HIV-1-specific T cell responses. |
| title_sort | definition of the viral targets of protective hiv 1 specific t cell responses |
| work_keys_str_mv | AT motheb definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT llanoa definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT ibarrondoj definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT danielsm definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT mirandac definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT zamarrenoj definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT bachv definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT zunigar definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT perezalvarezs definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT bergerc definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT puertasm definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT martinezpicadoj definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT rollandm definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT farfanm definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT szingerj definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT hildebrandw definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT yango definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT sanchezmerinov definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT brummec definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT brummez definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT heckermand definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT allent definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT mullinsj definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT gomezg definitionoftheviraltargetsofprotectivehiv1specifictcellresponses AT goulderp definitionoftheviraltargetsofprotectivehiv1specifictcellresponses |