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HIV-1 Conserved Mosaics Delivered by Regimens with Integration-deficient, DC-targeting Lentivirus Induce Robust T Cells

Ondondo, Beatrice and Wee, Edmund and McMichael, Andrew and Berglund, Peter and Archer, Jacob and Baltimore, David and Ter Meulen, Jan and Hanke, Tomas (2016) HIV-1 Conserved Mosaics Delivered by Regimens with Integration-deficient, DC-targeting Lentivirus Induce Robust T Cells. AIDS Research and Human Retroviruses, 32 (Suppl. 1). p. 344. ISSN 0889-2229.

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Background: To be effective against HIV-1, vaccine-induced T cells must selectively target functionally conserved and, at the same time, protective epitopes present on the majority of currently circulating and reactivated HIV-1 strains, and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising strategy towards achieving this goal, nevertheless, induction of robust longterm 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. Methods: 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. Results: Each of the two mosaics was individually immunogenic and together in heterologous prime-boost regimens with nonreplicating simian (chimpanzee) adenovirus or non-replicating poxvirus MVA vaccines induced very high frequencies of plurifunctional and broadly cross-reactive T cells in BALB/c and outbred CD1-SWISS mice. Conclusions: These data support further development of this vaccine concept.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 2016 Mary Ann Liebert.
Issue or Number:Suppl. 1
Record Number:CaltechAUTHORS:20161128-150950812
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Official Citation:AIDS Research and Human Retroviruses. October 2016, 32(S1): 1-409. doi:10.1089/aid.2016.5000.abstracts
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72338
Deposited By: Ruth Sustaita
Deposited On:28 Nov 2016 23:22
Last Modified:03 Oct 2019 16:16

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