Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects
<p>INTRODUCTION: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects w...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2017
|
| _version_ | 1826271613685858304 |
|---|---|
| author | Hancock, G Morón-López, S Kopycinski, J Puertas, M Giannoulatou, E Rose, A Salgado, M Hayton, E Crook, A Morgan, C Angus, B Chen, F Yang, H Martinez-Picado, J Hanke, T Dorrell, L |
| author_facet | Hancock, G Morón-López, S Kopycinski, J Puertas, M Giannoulatou, E Rose, A Salgado, M Hayton, E Crook, A Morgan, C Angus, B Chen, F Yang, H Martinez-Picado, J Hanke, T Dorrell, L |
| author_sort | Hancock, G |
| collection | OXFORD |
| description | <p>INTRODUCTION: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA). </p><p>METHODS: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA.HIVconsv (5.5 × 10(7) plaque-forming units, pfu, n = 8; 2.2 × 10(8) pfu, n = 7) or placebo (n = 4) at 0, 4 and 12 weeks. Magnitude, breadth and antiviral function of vaccine-induced T cells, cell-associated HIV-1 DNA in circulating CD4+ T cells and residual viremia in plasma were measured before and after vaccination.</p><p> RESULTS: 90% of subjects completed the vaccine regimen; there were no serious vaccine-related adverse events. The magnitude of HIVconsv-specific IFN-γ-secreting T cells was not significantly boosted in vaccinees when compared with placebos in ex vivo Elispot assays, due to greater than expected variation in HIV-specific T cell responses in the latter during the observation period. Ex vivo CD8+ T cell viral inhibitory capacity was modest but significantly increased post-vaccination with MVA.HIVconsv at the higher dose (p = 0.004) and was positively correlated with the frequency of HIVconsv-specific CD8+ CD107+ IFN-α± T cells (r = 0.57, p = 0.01). Total HIV-1 DNA and residual viral load did not change significantly from baseline in any group.</p><p> CONCLUSIONS: Homologous prime-boost vaccination with MVA.HIVconsv was safe in HIV-positive ART-treated subjects but showed modest immunogenicity and did not significantly change the size of the viral reservoir. MVA.HIVconsv may be more effective when used in a heterologous prime-boost vaccination regimen and when combined with a latency-reversing agent.</p><p> CLINICAL TRIALS REGISTRATION: NCT01024842.</p> |
| first_indexed | 2024-03-06T21:59:24Z |
| format | Journal article |
| id | oxford-uuid:4e12e154-ddee-4d63-a77c-0f493a46e816 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:59:24Z |
| publishDate | 2017 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:4e12e154-ddee-4d63-a77c-0f493a46e8162022-03-26T15:59:11ZEvaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjectsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e12e154-ddee-4d63-a77c-0f493a46e816EnglishSymplectic Elements at OxfordBioMed Central2017Hancock, GMorón-López, SKopycinski, JPuertas, MGiannoulatou, ERose, ASalgado, MHayton, ECrook, AMorgan, CAngus, BChen, FYang, HMartinez-Picado, JHanke, TDorrell, L<p>INTRODUCTION: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA). </p><p>METHODS: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA.HIVconsv (5.5 × 10(7) plaque-forming units, pfu, n = 8; 2.2 × 10(8) pfu, n = 7) or placebo (n = 4) at 0, 4 and 12 weeks. Magnitude, breadth and antiviral function of vaccine-induced T cells, cell-associated HIV-1 DNA in circulating CD4+ T cells and residual viremia in plasma were measured before and after vaccination.</p><p> RESULTS: 90% of subjects completed the vaccine regimen; there were no serious vaccine-related adverse events. The magnitude of HIVconsv-specific IFN-γ-secreting T cells was not significantly boosted in vaccinees when compared with placebos in ex vivo Elispot assays, due to greater than expected variation in HIV-specific T cell responses in the latter during the observation period. Ex vivo CD8+ T cell viral inhibitory capacity was modest but significantly increased post-vaccination with MVA.HIVconsv at the higher dose (p = 0.004) and was positively correlated with the frequency of HIVconsv-specific CD8+ CD107+ IFN-α± T cells (r = 0.57, p = 0.01). Total HIV-1 DNA and residual viral load did not change significantly from baseline in any group.</p><p> CONCLUSIONS: Homologous prime-boost vaccination with MVA.HIVconsv was safe in HIV-positive ART-treated subjects but showed modest immunogenicity and did not significantly change the size of the viral reservoir. MVA.HIVconsv may be more effective when used in a heterologous prime-boost vaccination regimen and when combined with a latency-reversing agent.</p><p> CLINICAL TRIALS REGISTRATION: NCT01024842.</p> |
| spellingShingle | Hancock, G Morón-López, S Kopycinski, J Puertas, M Giannoulatou, E Rose, A Salgado, M Hayton, E Crook, A Morgan, C Angus, B Chen, F Yang, H Martinez-Picado, J Hanke, T Dorrell, L Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects |
| title | Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects |
| title_full | Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects |
| title_fullStr | Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects |
| title_full_unstemmed | Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects |
| title_short | Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects |
| title_sort | evaluation of the immunogenicity and impact on the latent hiv 1 reservoir of a conserved region vaccine mva hivconsv in antiretroviral therapy treated subjects |
| work_keys_str_mv | AT hancockg evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT moronlopezs evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT kopycinskij evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT puertasm evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT giannoulatoue evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT rosea evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT salgadom evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT haytone evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT crooka evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT morganc evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT angusb evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT chenf evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT yangh evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT martinezpicadoj evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT hanket evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects AT dorrelll evaluationoftheimmunogenicityandimpactonthelatenthiv1reservoirofaconservedregionvaccinemvahivconsvinantiretroviraltherapytreatedsubjects |