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Published October 2016 | Published
Journal Article Open

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

Abstract

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.

Additional Information

© 2016 Mary Ann Liebert.

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August 20, 2023
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