Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adults
We are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not only epitopes) of the...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-01-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050117300311 |
| _version_ | 1819266846902190080 |
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| author | Gaudensia Mutua Bashir Farah Robert Langat Jackton Indangasi Simon Ogola Brian Onsembe Jakub T Kopycinski Peter Hayes Nicola J Borthwick Ambreen Ashraf Len Dally Burc Barin Annika Tillander Jill Gilmour Jan De Bont Alison Crook Drew Hannaman Josephine H Cox Omu Anzala Patricia E Fast Marie Reilly Kundai Chinyenze Walter Jaoko Tomáš Hanke |
| author_facet | Gaudensia Mutua Bashir Farah Robert Langat Jackton Indangasi Simon Ogola Brian Onsembe Jakub T Kopycinski Peter Hayes Nicola J Borthwick Ambreen Ashraf Len Dally Burc Barin Annika Tillander Jill Gilmour Jan De Bont Alison Crook Drew Hannaman Josephine H Cox Omu Anzala Patricia E Fast Marie Reilly Kundai Chinyenze Walter Jaoko Tomáš Hanke |
| author_sort | Gaudensia Mutua |
| collection | DOAJ |
| description | We are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not only epitopes) of the HIV-1 proteome, which are common to most global variants and which, if mutated, cause a replicative fitness loss. Our first clinical trial in low risk HIV-1-negative adults in Oxford demonstrated the principle that naturally mostly subdominant epitopes, when taken out of the context of full-length proteins/virus and delivered by potent regimens involving combinations of simian adenovirus and poxvirus modified vaccinia virus Ankara, can induce robust CD8+ T cells of broad specificities and functions capable of inhibiting in vitro HIV-1 replication. Here and for the first time, we tested this strategy in low risk HIV-1-negative adults in Africa. We showed that the vaccines were well tolerated and induced high frequencies of broadly HIVconsv-specific plurifunctional T cells, which inhibited in vitro viruses from four major clades A, B, C, and D. Because sub-Saharan Africa is globally the region most affected by HIV-1/AIDS, trial HIV-CORE 004 represents an important stage in the path toward efficacy evaluation of this highly rational and promising vaccine strategy. |
| first_indexed | 2024-12-23T21:07:46Z |
| format | Article |
| id | doaj.art-4f123ec4f6fe44898924201105e4aa3e |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-23T21:07:46Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-4f123ec4f6fe44898924201105e4aa3e2022-12-21T17:31:10ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012016-01-013C10.1038/mtm.2016.61Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adultsGaudensia Mutua0Bashir Farah1Robert Langat2Jackton Indangasi3Simon Ogola4Brian Onsembe5Jakub T Kopycinski6Peter Hayes7Nicola J Borthwick8Ambreen Ashraf9Len Dally10Burc Barin11Annika Tillander12Jill Gilmour13Jan De Bont14Alison Crook15Drew Hannaman16Josephine H Cox17Omu Anzala18Patricia E Fast19Marie Reilly20Kundai Chinyenze21Walter Jaoko22Tomáš Hanke23KAVI-Institute of Clinical Research, University of Nairobi, KenyaKAVI-Institute of Clinical Research, University of Nairobi, KenyaKAVI-Institute of Clinical Research, University of Nairobi, KenyaKAVI-Institute of Clinical Research, University of Nairobi, KenyaKAVI-Institute of Clinical Research, University of Nairobi, KenyaKAVI-Institute of Clinical Research, University of Nairobi, KenyaHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College, London, UKHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College, London, UKJenner Institute, University of Oxford, Oxford, UKHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College, London, UKEmmes Corporation, Rockville, Maryland, USAEmmes Corporation, Rockville, Maryland, USAKarolinska Institute, Stockholm, SwedenHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College, London, UKInternational AIDS Vaccine Initiative-New York, New York, New York, USAJenner Institute, University of Oxford, Oxford, UKICHOR Medical Systems, Inc., San Diego, California, USAHuman Immunology Laboratory, International AIDS Vaccine Initiative, Imperial College, London, UKKAVI-Institute of Clinical Research, University of Nairobi, KenyaInternational AIDS Vaccine Initiative-New York, New York, New York, USAKarolinska Institute, Stockholm, SwedenInternational AIDS Vaccine Initiative-New York, New York, New York, USAKAVI-Institute of Clinical Research, University of Nairobi, KenyaJenner Institute, University of Oxford, Oxford, UKWe are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not only epitopes) of the HIV-1 proteome, which are common to most global variants and which, if mutated, cause a replicative fitness loss. Our first clinical trial in low risk HIV-1-negative adults in Oxford demonstrated the principle that naturally mostly subdominant epitopes, when taken out of the context of full-length proteins/virus and delivered by potent regimens involving combinations of simian adenovirus and poxvirus modified vaccinia virus Ankara, can induce robust CD8+ T cells of broad specificities and functions capable of inhibiting in vitro HIV-1 replication. Here and for the first time, we tested this strategy in low risk HIV-1-negative adults in Africa. We showed that the vaccines were well tolerated and induced high frequencies of broadly HIVconsv-specific plurifunctional T cells, which inhibited in vitro viruses from four major clades A, B, C, and D. Because sub-Saharan Africa is globally the region most affected by HIV-1/AIDS, trial HIV-CORE 004 represents an important stage in the path toward efficacy evaluation of this highly rational and promising vaccine strategy.http://www.sciencedirect.com/science/article/pii/S2329050117300311 |
| spellingShingle | Gaudensia Mutua Bashir Farah Robert Langat Jackton Indangasi Simon Ogola Brian Onsembe Jakub T Kopycinski Peter Hayes Nicola J Borthwick Ambreen Ashraf Len Dally Burc Barin Annika Tillander Jill Gilmour Jan De Bont Alison Crook Drew Hannaman Josephine H Cox Omu Anzala Patricia E Fast Marie Reilly Kundai Chinyenze Walter Jaoko Tomáš Hanke Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adults Molecular Therapy: Methods & Clinical Development |
| title | Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adults |
| title_full | Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adults |
| title_fullStr | Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adults |
| title_full_unstemmed | Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adults |
| title_short | Broad HIV-1 inhibition in vitro by vaccine-elicited CD8+ T cells in African adults |
| title_sort | broad hiv 1 inhibition in vitro by vaccine elicited cd8 t cells in african adults |
| url | http://www.sciencedirect.com/science/article/pii/S2329050117300311 |
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