Journal
VACCINE
Volume 32, Issue 47, Pages 6266-6276Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2014.09.010
Keywords
HIV immunogens; Polylactic acid (PLA) particles; MVA; Human monocytes derived-dendritic cells; Human CD4(+) T and CD8(+) T-cells; Proliferation; Cytokines; HIV core protein p24
Categories
Funding
- Spanish Ministry of Health [FIS2006-1259, FIS 2009-80145, FIS 2010-02984, FIS 2012-01247, FIS 2009-11078]
- Spanish Ministry of Health (RIS-Spanish Cooperative Network on AIDS Research)
- Spanish Foundation for AIDS Research [FIPSE 36344/02, 36536-05, 36551/06]
- Fundacion Botin
- EU [EuroVac QLRT-PL-1999-01321, QLK2-CT-2002-01867]
- ANR (French National Research Agency)
- PESCDELLI
- ANABIO
- Fondation Recherche Medicale (FRM)
- Pierre Berge funding (Sidaction)
- FP7 European grant CUT'HIVAC [241904]
- FP7 European grant [280873]
- [MuNanoVac-EU-STREP-037200]
- [108821-55-RGRL]
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Since recent data suggest that nanoparticles and modified vaccinia ankara (MVA) vectors could play a pivotal role in HIV-1 therapeutics and vaccine design, in an ex vivo model of human monocyte-derived dendritic cells (MDDCs), we compared two different loading strategies with HIV-1 vaccine vehicles, either viral or synthetic derived. We used polylactic acid (PLA) colloidal biodegradable particles, coated with HIV Gag antigens (p24), and MVA expressing Gag (rMVA-gag and rMVA-gag/trans membrane) or Tat, Nef and Rev genes (rMVA tat + rev and rMVA net). PLA-p24 captured by MDDCs from HIV-1 individuals induced a slight degree of MDDC maturation, cytokine and chemokine secretion and migration towards a gradient of CCL19 chemokine and highly increased HIV-specific CD8(+) T-cell proliferation compared with p24 alone. After complete maturation induction of PLA-p24-pulsed MDDCs, maximal migration towards a gradient of CCL19 chemokine and induction of HIV-specific T-cell proliferation (two-fold higher for CD4(+) than CD8(+)) and cytokine secretion (IFN-gamma and IL-2) in the co-culture were observed. Upon exposure to MVA-gag, MDDCs produced cytokines and chemokines and maintained their capacity to migrate to a gradient of CCL19. MDDCs infected with MVA-gag and MVA-gag trans-membrane were able to induce HIV-specific CD8(+) proliferation and secretion of IFN-gamma, IL-2, IL-6 and TNF-alpha. We conclude that both HIV antigens loading strategies (PLA-p24 nanoparticles or MVA expressing HIV genes) induce HIV-1-specific T-cell responses, which are able to kill autologous gag-expressing cells. Thus, they are plausible candidates for the development of anti-HIV vaccines. (C) 2014 Elsevier Ltd. All rights reserved.
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