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Uriel Y. Moreno- Nieves PhD Student

DC infected by the ANRS MVA HIV vaccine candidate prime NK cells with anti-HIV specific activity through a mechanism involving NKG2D and NKp46 on NK cells and membrane-bound IL-15 on DC. Uriel Y. Moreno- Nieves PhD Student. Introduction. NK cells : Anti-viral activity.

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Uriel Y. Moreno- Nieves PhD Student

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  1. DC infected by the ANRS MVAHIV vaccine candidate prime NK cells with anti-HIV specific activity through a mechanism involving NKG2D and NKp46 on NK cells and membrane-bound IL-15 on DC Uriel Y. Moreno-Nieves PhDStudent

  2. Introduction • NK cells : • Anti-viral activity. • First line of defense against viral pathogens. • Increasing evidence of adaptive immune features. • Cross-talk NK/DC: • Activation of NK cells. • Important for the induction of adaptive immunity. • MVA : Modified Vaccinia virus Ankara • Attenuated, non-replicating poxvirus. • MVAHIV : expression of Gag, Pol, Nef peptides.

  3. Background and Objectives • NK cells stimulated by MVAHIV-infected DC are able to better control HIV infection in DC. Objectives: • To test control of HIV-1 infection in other cell types by MVAHIV-stimulated NK cells. • To investigate the mechanisms of anti-HIV specific priming of NK cells.

  4. Material and methods CD4+ T cells PBMC Magnetic separation Ficoll NK cells Blood from Healthy donors Differentiation 7 days Monocytes DC Addition of DC and NK cells after 18 hours Control of HIV infection DC CD4+ T cells Analysis of anti-HIV specificity Infection of DC by MVA Priming of NK cells 4 days

  5. Control of HIV infection by NK cells is increased after MVAHIV priming Control of HIV infection HIV-infected DC DC CD4+ T cell Analysis of anti-HIV specificity Priming of NK cells 4 days CMV-infected DC HIV-infected CD4+ T cells Day 6 p.i. n=10 Day 7 and Day 10 p.i. n=8 and n=10

  6. Priming of NK cells by MVAHIV is modulated by NKG2D HIV-infected CD4+ T cells HIV-infected DC Day 7 p.i. n=8 Day 9 p.i. n=10

  7. NKG2D blockade during MVA priming decreases mbIL-15 expression on DC Expression of mbIL-15 on DC during MVA priming Modulation of mbIL-15 on DC by NKG2D and NKp46 24, 48 and 72 hours of priming n=7 72 hours of priming n=5

  8. IL-15 is important for the MVAHIV priming Implication of NKG2D and mbIL-15 during MVA priming Day 9 p.i. n=8

  9. Conclusions • NK cells primed by MVAHIV have increased anti-HIV activity. • Better control of HIV infection in DC and CD4+ T cells. • MVAHIV priming seems to be anti-HIV-1 specific. • NKp46 blockade during MVAHIV priming enhances subsequent control of HIV infection in DC. • NKG2D engagement during MVAHIVpriming is important for subsequent control of HIV infection in DC and CD4+T cells. • NKG2D regulates mbIL-15 expression on DC. • IL-15 is important for MVAHIVpriming. • Decreased mbIL-15 expression after NKG2D blockade during MVAHIV priming might be responsible for the decreased control of HIV infection in CD4+ T cells. • Possible contribution of NK cells in vaccine efficacy.

  10. Acknowledgements Daniel Scott-Algara Françoise Barré-Sinoussi Yves Lévy Jean-Saville Cummings Vincent Arnold Adrien Gilbert Kevin Yarbrough Céline Didier Thank you!

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