HIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cells
To be effective against HIV-1, vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clini...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Published: |
Elsevier
2016
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| _version_ | 1797064332037586944 |
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| author | Hanke, T Wee, E Ondondo, B Berglund, P Archer, J McMichael, A Baltimore, D ter Meulen, J |
| author_facet | Hanke, T Wee, E Ondondo, B Berglund, P Archer, J McMichael, A Baltimore, D ter Meulen, J |
| author_sort | Hanke, T |
| collection | OXFORD |
| description | To be effective against HIV-1, vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clinical status and control of HIV-1 replication), and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising vaccine strategies, nevertheless, induction of robust long-term memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low antivector immune responses. Here, we describe construction of novel candidate vaccines ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an integration-deficient lentiviral vector platform with preferential transduction of human dendritic cells and express bivalent mosaic of conserved-region T-cell immunogens with a high global HIV-1 match. Each of the two mosaic vaccines was individually immunogenic. When administered together in heterologous prime-boost regimens with chimpanzee adenovirus and/or poxvirus MVA vaccines to BALB/c and outbred CD1-Swiss mice, they induced median frequency of over 6,000 T-cells/10^6 splenocytes, which were plurifunctional, broadly specific and cross-reactive. These results support further development of this vaccine concept. |
| first_indexed | 2024-03-06T21:12:45Z |
| format | Journal article |
| id | oxford-uuid:3ebc7666-d089-4af3-9234-f3fd0e4fd995 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:12:45Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:3ebc7666-d089-4af3-9234-f3fd0e4fd9952022-03-26T14:27:21ZHIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3ebc7666-d089-4af3-9234-f3fd0e4fd995Symplectic Elements at OxfordElsevier2016Hanke, TWee, EOndondo, BBerglund, PArcher, JMcMichael, ABaltimore, Dter Meulen, JTo be effective against HIV-1, vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clinical status and control of HIV-1 replication), and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising vaccine strategies, nevertheless, induction of robust long-term memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low antivector immune responses. Here, we describe construction of novel candidate vaccines ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an integration-deficient lentiviral vector platform with preferential transduction of human dendritic cells and express bivalent mosaic of conserved-region T-cell immunogens with a high global HIV-1 match. Each of the two mosaic vaccines was individually immunogenic. When administered together in heterologous prime-boost regimens with chimpanzee adenovirus and/or poxvirus MVA vaccines to BALB/c and outbred CD1-Swiss mice, they induced median frequency of over 6,000 T-cells/10^6 splenocytes, which were plurifunctional, broadly specific and cross-reactive. These results support further development of this vaccine concept. |
| spellingShingle | Hanke, T Wee, E Ondondo, B Berglund, P Archer, J McMichael, A Baltimore, D ter Meulen, J HIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cells |
| title | HIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cells |
| title_full | HIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cells |
| title_fullStr | HIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cells |
| title_full_unstemmed | HIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cells |
| title_short | HIV-1 conserved mosaics delivered by regimens with integration-deficient, DC-targeting lentiviral vector induce robust T cells |
| title_sort | hiv 1 conserved mosaics delivered by regimens with integration deficient dc targeting lentiviral vector induce robust t cells |
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