Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial

Miner, Maurine D.; deCamp, Allan; Grunenberg, Nicole; De Rosa, Stephen C.; Fiore-Gartland, Andrew; Bar, Katherine; Spearman, Paul; Allen, Mary; Yu, Pei-Chun; Manso, Bryce; Frahm, Nicole; Kalams, Spyros; Baden, Lindsey; Keefer, Michael C.; Scott, Hyman M.; Novak, Richard; Van Tieu, Hong; Tomaras, Georgia D.; Kublin, James G.; McElrath, M. Juliana; Corey, Lawrence; Frank, Ian; Kalichman, Artur; Edlefsen, Paul; Enama, Mary; Hural, John; Holt, Renee; Dunbar, Debora; Crawford, Dave; Maki, Ian; Johannessen, Jan; Estep, Scharla; Grigoriev, Yevgeny; Madenwald, Tamra; Hansen, Marianne; Holman, Drienna; Fair, Ramey; Meyer, Genevieve; Luke-Kilolam, Anya

doi:10.1016/j.ebiom.2024.104987

Cited by 2 publications

References 49 publications

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Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

Sánchez-Cerrillo,

Popova,

Agudo-Lera

et al. 2024

Preprint

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Natural Killer (NK) cells are promising tools for the development of immunotherapies targeting persistently infected CD4+ T cells to potentially achieve remission in people with HIV-1 (PWH). However, the chronicity of HIV-1 infection limits the functional properties of NK cells, and additional approaches are needed to potentiate their cytotoxic activity against HIV-1-infected cells. In the present study, we analyzed the reinvigoration of functional NK cells from PWH after priming with autologous dendritic cells (DC) stimulated with nanoparticles containing Poly I:C (Nano-PIC). We show that improved natural cytotoxic function in NK cell from PWH associates with increased proportions of NKG2C+CD57- precursors of memory NK, which eliminate HIV-1 infected CD4+ T cells mainly through the TRAIL receptor. In addition, expression of TIGIT but not TIM3 limited increase in NKG2C+ memory NK cell precursors and associated with persistent dysfunctionality of NK cells after stimulation with Nano PIC-DC. Blockade of TIGIT restored functional capacities of NK cell from PWH eliminating HIV-1 infected cellsin vitro. Moreover, combining of NK cell and Nano-PIC-DC with anti-TIGIT mAbs immunotherapy limited the expansion of HIV-1 infected cells in humanized immunodeficient NSG mice transplanted with CD4+ T cells from PWHin vivo. Such viral control was associated with preserved NKG2C memory NK cell precursors, increased expression of granzyme B and TRAIL on NK in tissue from transplanted NSG mice. Together, combination of Nano-PIC DC and anti-TIGIT antibodies may be a promising strategy to increase the efficacy of immunotherapies aimed at HIV-1 cure.One sentence summaryStimulation of memory NK with a combination of DC and anti-TIGIT antibodies increase their ability to eliminate HIV-1 infected CD4+ T cellsin vitroandin vivo.

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Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

Sánchez-Cerrillo,

Popova,

Agudo-Lera

et al. 2024

Preprint

View full text Add to dashboard Cite

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HIV Vaccine Development at a Crossroads: New B and T Cell Approaches

Govindan,

Stephenson

2024

Vaccines

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Despite rigorous scientific efforts over the forty years since the onset of the global HIV pandemic, a safe and effective HIV-1 vaccine remains elusive. The challenges of HIV vaccine development have proven immense, in large part due to the tremendous sequence diversity of HIV and its ability to escape from antiviral adaptive immune responses. In recent years, several phase 3 efficacy trials have been conducted, testing a similar hypothesis, e.g., that non-neutralizing antibodies and classical cellular immune responses could prevent HIV-1 acquisition. These studies were not successful. As a result, the field has now pivoted to bold novel approaches, including sequential immunization strategies to drive the generation of broadly neutralizing antibodies and human CMV-vectored vaccines to elicit MHC-E-restricted CD8+ T cell responses. Many of these vaccine candidates are now in phase 1 trials, with early promising results.

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Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial

Cited by 2 publications

References 49 publications

Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells

HIV Vaccine Development at a Crossroads: New B and T Cell Approaches

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