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Review

Enhancing dendritic cell activation and HIV vaccine effectiveness through nanoparticle vaccination

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Pages 719-729 | Received 17 Nov 2015, Accepted 08 Jan 2016, Published online: 26 Feb 2016

References

  • Etheridge ML, Campbell SA, Erdman AG, et al. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine: NBM. 2013;9(1):1–14.
  • Sainz V, Conniot J, Matos AI, et al. Regulatory aspects on nanomedicines. Biochem Biophys Res Commun. 2015;468:504–510.
  • Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338(13):853–860.
  • Wainberg MA, Zaharatos GJ, Brenner BG. Development of antiretroviral drug resistance. N Engl J Med. 2011;365(7):637–646.
  • Buell KG, Chung C, Chaudhry Z, et al. Lifelong antiretroviral therapy or HIV cure: the benefits for the individual patient. AIDS Care. 2015;1–5. doi:10.1080/09540121.2015.1074653
  • WHO. HIV/AIDS fact sheet. 2014. [cited 2015 Nov 7]. Available from: http://www.who.int/mediacentre/factsheets/fs360/en/.
  • Rappuoli R, Aderem AA. 2020 vision for vaccines against HIV, tuberculosis and malaria. Nature. 2011;473(7348):463–469.
  • Johnston MI, Fauci AS. An HIV vaccine—evolving concepts. N Engl J Med. 2007;356(20):2073–2081.
  • Gaschen B, Taylor J, Yusim K, et al. Diversity considerations in HIV-1 vaccine selection. Science. 2002;296(5577):2354–2360.
  • Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet. 2014;384(9939):258–271.
  • McCoy LE, Weiss RA. Neutralizing antibodies to HIV-1 induced by immunization. J Exp Med. 2013;210(2):209–223.
  • Bordon Y. Immunotherapy: checkpoint parley. Nat Rev Cancer. 2015;15(1):3–3.
  • Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008;372(9653):1881–1893.
  • McElrath MJ, De Rosa SC, Moodie Z, et al. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case–cohort analysis. Lancet. 2008;372(9653):1894–1905.
  • Rolland M, Tovanabutra S, Frahm N, et al. Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial. Nat Med. 2011;17(3):366–371.
  • Iaccino E, Schiavone M, Fiume G, et al. The aftermath of the Merck’s HIV vaccine trial. Retrovirology. 2008;5(1):56.
  • Duerr A, Huang Y, Buchbinder S, et al. Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study). J Infect Dis. 2012;206(2):158–266.
  • Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361(23):2209–2220.
  • Prentice HA, Tomaras GD, Geraghty DE, et al. HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition. Sci Trans Med. 2015;7(296):296ra112–296ra112.
  • Corey L, Gilbert PB, Tomaras GD, et al. Immune correlates of vaccine protection against HIV-1 acquisition. Sci Trans Med. 2015;7(310):310rv317–310rv317.
  • Chung AW, Ghebremichael M, Robinson H, et al. Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines. Sci Trans Med. 2014;6(228):228ra238–228ra238.
  • Haynes BF, Gilbert PB, McElrath MJ, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366(14):1275–1286.
  • Kastenmüller W, Kastenmüller K, Kurts C, et al. Dendritic cell-targeted vaccines – hope or hype? Nat Rev Immunol. 2014;14(10):705–711.
  • Altfeld M, Fadda L, Frleta D, et al. DCs and NK cells: critical effectors in the immune response to HIV-1. Nat Rev Immunol. 2011;11(3):176–186.
  • Posch W, Lass-Flörl C, Wilflingseder D. Role of dendritic cell subsets on HIV-specific immunity. Rijeka: INTECH Open Access Publisher; 2013.
  • Dutertre C-A, Wang L-F, Ginhoux F. Aligning bona fide dendritic cell populations across species. Cell Immunol. 2014;291(1):3–10.
  • Schlitzer A, Ginhoux F. Organization of the mouse and human DC network. Curr Opin Immunol. 2014;26:90–99.
  • Poulin LF, Salio M, Griessinger E, et al. Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells. J Exp Med. 2010;207(6):1261–1271.
  • Shortman K, Lahoud MH, Caminschi I. Improving vaccines by targeting antigens to dendritic cells. Exp Mol Med. 2009;41(2):61–66.
  • Tacken PJ, Zeelenberg IS, Cruz LJ, et al. Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity. Blood. 2011;118(26):6836–6844.
  • Climent N, Munier S, Piqué N, et al. Loading dendritic cells with PLA-p24 nanoparticles or MVA expressing HIV genes induces HIV-1-specific T cell responses. Vaccine. 2014;32(47):6266–6276.
  • Climent N, Pavot V, García F, et al. Co-delivery of antigen p24 and NOD-ligands by PLA nanoparticles to human dendritic cells promote highly functional HIV-1-specific T-cell responses. AIDS Res Hum Retroviruses. 2014;30(S1):A240–A241.
  • Lebel M-È, Daudelin J-F, Chartrand K, et al. Nanoparticle adjuvant sensing by TLR7 enhances CD8+ T cell–mediated protection from Listeria monocytogenes infection. J Immunol. 2014;192(3):1071–1078.
  • Hanson MC, Crespo MP, Abraham W, et al. Nanoparticulate STING agonists are potent lymph node–targeted vaccine adjuvants. J Clin Invest. 2015;125(125 (6)):2532–2546.
  • Lynn GM, Laga R, Darrah PA, et al. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nat Biotechnol. 2015;33(11):1201–1210.
  • Sun B, Ji Z, Liao Y-P, et al. Engineering an effective immune adjuvant by designed control of shape and crystallinity of aluminum oxyhydroxide nanoparticles. ACS Nano. 2013;7(12):10834–10849.
  • Thomas SN, van der Vlies AJ, O’Neil CP, et al. Engineering complement activation on polypropylene sulfide vaccine nanoparticles. Biomaterials. 2011;32(8):2194–2203.
  • Shima F, Akagi T, Uto T, et al. Manipulating the antigen-specific immune response by the hydrophobicity of amphiphilic poly (γ-glutamic acid) nanoparticles. Biomaterials. 2013;34(37):9709–9716.
  • Moyano DF, Goldsmith M, Solfiell DJ, et al. Nanoparticle hydrophobicity dictates immune response. J Am Chem Soc. 2012;134(9):3965–3967.
  • Williams GR, Fierens K, Preston SG, et al. Immunity induced by a broad class of inorganic crystalline materials is directly controlled by their chemistry. J Exp Med. 2014;211(6):1019–1025.
  • Niikura K, Matsunaga T, Suzuki T, et al. Gold nanoparticles as a vaccine platform: influence of size and shape on immunological responses in vitro and in vivo. ACS Nano. 2013;7(5):3926–3938.
  • Dykman L, Khlebtsov N. Gold nanoparticles in biomedical applications: recent advances and perspectives. Chem Soc Rev. 2012;41(6):2256–2282.
  • Xu L, Liu Y, Chen Z, et al. Surface-engineered gold nanorods: promising DNA vaccine adjuvant for HIV-1 treatment. Nano Lett. 2012;12(4):2003–2012.
  • le Guével X, Palomares F, Torres MJ, et al. Nanoparticle size influences the proliferative responses of lymphocyte subpopulations. RSC Adv. 2015;5(104):85305–85309.
  • Tomić S, Đokić J, Vasilijić S, et al. Size-dependent effects of gold nanoparticles uptake on maturation and antitumor functions of human dendritic cells in vitro. PLOS One. 2014;9(5):e96584.
  • Albanese A, Tang PS, Chan WCW. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng. 2012;14:1–16.
  • Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012;7:5577.
  • Zhao L, Seth A, Wibowo N, et al. Nanoparticle vaccines. Vaccine. 2014;32(3):327–337.
  • Foged C, Brodin B, Frokjaer S, et al. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm. 2005;298(2):315–322.
  • Kim H, Uto T, Akagi T, et al. Amphiphilic poly (amino acid) nanoparticles induce size‐dependent dendritic cell maturation. Adv Funct Mater. 2010;20(22):3925–3931.
  • Joshi VB, Geary SM, Salem AK. Biodegradable particles as vaccine delivery systems: size matters. Aaps J. 2013;15(1):85–94.
  • Wischke C, Borchert -H-H, Zimmermann J, et al. Stable cationic microparticles for enhanced model antigen delivery to dendritic cells. J Control Release. 2006;114(3):359–368.
  • Thiele L, Merkle HP, Walter E. Phagocytosis and phagosomal fate of surface-modified microparticles in dendritic cells and macrophages. Pharm Res. 2003;20(2):221–228.
  • Lunov O, Syrovets T, Loos C, et al. Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. ACS Nano. 2011;5(3):1657–1669.
  • Le Guével X, Perrez Perrino M, Fernández TD, et al. Multivalent glycosylation of fluorescent gold nanoclusters promotes increased human dendritic cell targeting via multiple endocytic pathways. ACS Appl Mater Interfaces. 2015;7(37):20945–20956.
  • Joffre OP, Segura E, Savina A, et al. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012;12(8):557–569.
  • Tel J, Sittig SP, Blom RAM, et al. Targeting uptake receptors on human plasmacytoid dendritic cells triggers antigen cross-presentation and robust type I IFN secretion. J Immunol. 2013;191(10):5005–5012.
  • Segura E, Durand M, Amigorena S. Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ–resident dendritic cells. J Exp Med. 2013;210(5):1035–1047.
  • Reuter A, Panozza SE, Macri C, et al. Criteria for dendritic cell receptor selection for efficient antibody-targeted vaccination. J Immunol. 2015;194(6):2696–2705.
  • Mintern JD, Percival C, Kamphuis MMJ, et al. Targeting dendritic cells: the role of specific receptors in the internalization of polymer capsules. Adv Healthc. 2013;2(7):940–944.
  • Caminschi I, Proietto AI, Ahmet F, et al. The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement. Blood. 2008;112(8):3264–3273.
  • Idoyaga J, Lubkin A, Fiorese C, et al. Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc Natl Acad Sci USA. 2011;108(6):2384–2389.
  • Li J, Ahmet F, Sullivan LC, et al. Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non‐human primates. Eur J Immunol. 2015;45(3):854–864.
  • Sehgal K, Ragheb R, Fahmy TM, et al. Nanoparticle-mediated combinatorial targeting of multiple human dendritic cell (DC) subsets leads to enhanced T cell activation via IL-15–dependent DC crosstalk. J Immunol. 2014;193(5):2297–2305.
  • Bertrand N, Leroux J-C. The journey of a drug-carrier in the body: an anatomo-physiological perspective. J Control Release. 2012;161(2):152–163.
  • Perry JL, Reuter KG, Kai MP, et al. PEGylated PRINT nanoparticles: the impact of PEG density on protein binding, macrophage association, biodistribution, and pharmacokinetics. Nano Lett. 2012;12(10):5304–5310.
  • Yang Q, Jones SW, Parker CL, et al. Evading immune cell uptake and clearance requires PEG grafting at densities substantially exceeding the minimum for brush conformation. Mol Pharm. 2014;11(4):1250–1258.
  • Cui J, De Rose R, Alt K, et al. Engineering poly(ethylene glycol) particles for improved biodistribution. ACS Nano. 2015;9(2):1571–1580.
  • Segura E, Valladeau-Guilemond J, Donnadieu M-H, et al. Characterization of resident and migratory dendritic cells in human lymph nodes. J Exp Med. 2012;209(4):653–660.
  • Thomas SN, Schudel A. Overcoming transport barriers for interstitial-, lymphatic-, and lymph node-targeted drug delivery. Curr Opin Chem Eng. 2015;7:65–74.
  • Liu H, Moynihan KD, Zheng Y, et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature. 2014;507(7493):519–522.
  • Iwasaki A. Antiviral immune responses in the genital tract: clues for vaccines. Nat Rev Immunol. 2010;10(10):699–711.
  • Woodrow KA, Bennett KM, Lo DD. Mucosal vaccine design and delivery. Annu Rev Biomed Eng. 2012;14:17–46.
  • Ensign LM, Tang BC, Wang -Y-Y, et al. Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci Trans Med. 2012;4(138):138ra179–138ra179.
  • Yu T, Wang -Y-Y, Yang M, et al. Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly (lactic-co-glycolic acid). Drug Deliv Transl Res. 2012;2(2):124–128.
  • Lai SK, Suk JS, Pace A, et al. Drug carrier nanoparticles that penetrate human chronic rhinosinusitis mucus. Biomaterials. 2011;32(26):6285–6290.
  • Suk JS, Kim AJ, Trehan K, et al. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. J Control Release. 2014;178:8–17.
  • Maisel K, Ensign L, Reddy M, et al. Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse. J Control Release. 2015;197:48–57.
  • Ensign LM, Lai SK, Wang -Y-Y, et al. Pretreatment of human cervicovaginal mucus with pluronic F127 enhances nanoparticle penetration without compromising mucus barrier properties to herpes simplex virus. Biomacromolecules. 2014;15(12):4403–4409.
  • Mastorakos P, da Silva AL, Chisholm J, et al. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc Natl Acad Sci USA. 2015;112(28):8720–8725.
  • Xie Z, Ji Z, Zhang Z, et al. Adenoviral vectors coated with cationic PEG derivatives for intravaginal vaccination against HIV-1. Biomaterials. 2014;35(27):7896–7908.
  • Coco R, Plapied L, Pourcelle V, et al. Drug delivery to inflamed colon by nanoparticles: comparison of different strategies. Int J Pharm. 2013;440(1):3–12.
  • Baggaley RF, White RG, Boily M-C. HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention. Int J Epidemiol. 2010;39(4):1048–1063.
  • Tan H-X, Kent SJ, De Rose R. Contemporary HIV vaccines: tissue resident T-cells and strategies to prevent mucosal infection. Curr Top Med Chem. 2015. PMID 26324042.
  • Ramanathan R, Park J, Hughes SM, et al. Effect of mucosal cytokine administration on selective expansion of vaginal dendritic cells to support nanoparticle transport. Am J Reprod Immunol. 2015;74(4):333–344.
  • Granelli-Piperno A, Shimeliovich I, Pack M, et al. HIV-1 selectively infects a subset of nonmaturing BDCA1-positive dendritic cells in human blood. J Immunol. 2006;176(2):991–998.
  • Gringhuis SI, van der Vlist M, van den Berg LM, et al. HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat Immunol. 2010;11(5):419–426.
  • Manches O, Frleta D, Bhardwaj N. Dendritic cells in progression and pathology of HIV infection. Trends Immunol. 2014;35(3):114–122.
  • Zhang W, Wang L, Liu Y, et al. Immune responses to vaccines involving a combined antigen–nanoparticle mixture and nanoparticle-encapsulated antigen formulation. Biomaterials. 2014;35(23):6086–6097.
  • Liard C, Munier S, Arias M, et al. Targeting of HIV-p24 particle-based vaccine into differential skin layers induces distinct arms of the immune responses. Vaccine. 2011;29(37):6379–6391.
  • Klein F, Mouquet H, Dosenovic P, et al. Antibodies in HIV-1 vaccine development and therapy. Science. 2013;341(6151):1199–1204.
  • Chen J, Kovacs JM, Peng H, et al. Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein. Science. 2015;349(6244):191–195.
  • Sanders RW, van Gils MJ, Derking R, et al. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science. 2015;349(6244):aac4223.
  • Klein JS, Bjorkman PJ. Few and far between: how HIV may be evading antibody avidity. PLoS Pathog. 2010;6(5):e1000908.
  • Schiller J, Chackerian B. Why HIV virions have low numbers of envelope spikes: implications for vaccine development. PLoS Pathog. 2014;10(8):e1004254.
  • Pejawar-Gaddy S, Kovacs JM, Barouch DH, et al. Design of lipid nanocapsule delivery vehicles for multivalent display of recombinant env trimers in HIV vaccination. Bioconjugate Chem. 2014;25(8):1470–1478.
  • Verkoczy L, Kelsoe G, Haynes BF. HIV-1 envelope gp41 broadly neutralizing antibodies: hurdles for vaccine development. PLoS Pathog. 2014;10(5):e1004073.
  • Wahome N, Pfeiffer T, Ambiel I, et al. Conformation‐specific display of 4E10 and 2F5 epitopes on self‐assembling protein nanoparticles as a potential HIV vaccine. Chem Biol Drug Des. 2012;80(3):349–357.
  • Hanson MC, Abraham W, Crespo MP, et al. Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides. Vaccine. 2015;33(7):861–868.
  • Leaman DP, Lee JH, Ward AB, et al. Immunogenic display of purified chemically crosslinked HIV-1 spikes. J Virol. 2015;JVI:03738–03714.
  • Chung AW, Kumar MP, Arnold KB, et al. Dissecting polyclonal vaccine-induced humoral immunity against HIV using systems serology. Cell. 2015;163(4):988–998.
  • Barouch DH, Alter G, Broge T, et al. Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. Science. 2015;349(6245):320–324.
  • Bournazos S, Klein F, Pietzsch J, et al. Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell. 2014;158(6):1243–1253.
  • Hessell AJ, Hangartner L, Hunter M, et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature. 2007;449(7158):101–104.
  • Jegerlehner A, Schmitz N, Storni T, et al. Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. J Immunol. 2004;172(9):5598–5605.
  • DiLillo DJ, Tan GS, Palese P, et al. Broadly neutralizing hemagglutinin stalk-specific antibodies require Fc [gamma] R interactions for protection against influenza virus in vivo. Nat Med. 2014;20(2):143–151.
  • Yassine HM, Boyington JC, McTamney PM, et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015;21(9):1065–1070.
  • Beck Z, Matyas GR, Jalah R, et al. Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21. Vaccine. 2015;33(42):5578–5587.
  • Keller S, Wilson JT, Patilea GI, et al. Neutral polymer micelle carriers with pH-responsive, endosome-releasing activity modulate antigen trafficking to enhance CD8+ T cell responses. J Control Release. 2014;191:24–33.
  • Benjaminsen RV, Mattebjerg MA, Henriksen JR, et al. The possible “proton sponge” effect of polyethylenimine (PEI) does not include change in lysosomal pH. Mol Ther. 2013;21(1):149–157.
  • Chen J, Li Z, Huang H, et al. Improved antigen cross-presentation by polyethyleneimine-based nanoparticles. Int J Nanomedicine. 2011;6:77–84.
  • Qi L, Shao W, Shi D. JAM-2 siRNA intracellular delivery and real-time imaging by proton-sponge coated quantum dots. J Mater Chem B. 2013;1(5):654–660.
  • Varkouhi AK, Scholte M, Storm G, et al. Endosomal escape pathways for delivery of biologicals. J Control Release. 2011;151(3):220–228.
  • Sayers EJ, Cleal K, Eissa NG, et al. Distal phenylalanine modification for enhancing cellular delivery of fluorophores, proteins and quantum dots by cell penetrating peptides. J Control Release. 2014;195:55–62.
  • Ye S-F, Tian M-M, Wang T-X, et al. Synergistic effects of cell-penetrating peptide Tat and fusogenic peptide HA2-enhanced cellular internalization and gene transduction of organosilica nanoparticles. Nanomedicine: NBM. 2012;8(6):833–841.
  • Tang J, Yin R, Tian Y, et al. A novel self-assembled nanoparticle vaccine with HIV-1 Tat 49-57/HPV16 E7 49-57 fusion peptide and GM-CSF DNA elicits potent and prolonged CD8+ T cell-dependent anti-tumor immunity in mice. Vaccine. 2012;30(6):1071–1082.
  • Cheng CJ, Tietjen GT, Saucier-Sawyer JK, et al. A holistic approach to targeting disease with polymeric nanoparticles. Nat Rev Drug Discov. 2015;14(4):239–247.
  • Liu D, Auguste DT. Cancer targeted therapeutics: from molecules to drug delivery vehicles. J Control Release. 2015;219:632–643.
  • Roy U, Rodríguez J, Barber P, et al. The potential of HIV-1 nanotherapeutics: from in vitro studies to clinical trials. Nanomedicine. 2015;10(24):3597–3609.
  • ClinicalTrials Database: NCT02549040. [cited 2015 Nov 7]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT02549040.
  • ClinicalTrials Database: NCT02165202. [cited 2015 Nov 7]. Available from: https://clinicaltrials.gov/ct2/show/NCT02165202.
  • ClinicalTrials Database: NCT02076178. [cited 2015 Nov 7]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT02076178
  • ClinicalTrials Database: NCT00712530. [cited 2015 Nov 7]. Available from: https://clinicaltrials.gov/ct2/show/NCT00712530.
  • ClinicalTrials Database: NCT00711230. [cited 2015 Nov 17]. Available from: https://clinicaltrials.gov/ct2/show/NCT00711230.
  • Deeks SG, Autran B, Berkhout B, et al. Towards an HIV cure: a global scientific strategy. Nat Rev Immunol. 2012;12(8):607–614.
  • Deeks SG. HIV: shock and kill. Nature. 2012;487(7408):439–440.
  • Barouch DH, Deeks SG. Immunologic strategies for HIV-1 remission and eradication. Science. 2014;345(6193):169–174.
  • Tinkle S, McNeil SE, Mühlebach S, et al. Nanomedicines: addressing the scientific and regulatory gap. Ann New York Acad Sci. 2014;1313(1):35–56.

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