Nanoparticle-based delivery platforms for mRNA vaccine development

Sezer Okay; Öznur Özge Özcan; Mesut Karahan; Sezer Okay; Öznur Özge Özcan; Mesut Karahan

doi:10.3934/biophy.2020023

AIMS Biophysics

2020, Volume 7, Issue 4: 323-338. doi: 10.3934/biophy.2020023

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Nanoparticle-based delivery platforms for mRNA vaccine development

1.
Department of Vaccine Technology, Vaccine Institute, Hacettepe University, Ankara, Turkey
2.
Department of Molecular Neuroscience, Institute of Health Sciences, Üsküdar University, Istanbul, Turkey
3.
Department of Nutrition and Dietetics, Faculty of Health Sciences, Üsküdar University, Istanbul, Turkey

Received: 21 June 2020 Accepted: 16 August 2020 Published: 20 August 2020

Conventional vaccines have saved millions of lives, and new vaccines have also been developed; however, an urgent need for an efficient vaccine against SARS-CoV-2 showed us that vaccine development technologies should be improved more to obtain prophylactic agents rapidly during pandemic diseases. One of the next-generation vaccine technologies is utilization of mRNA molecules encoding antigens. The mRNA vaccines offer many advantages compared to conventional and other subunit vaccines. For instance, mRNA vaccines are relatively safe since they do not cause disease and mRNA does not integrate into the genome. mRNA vaccines also provide diverse types of immune responses resulting in the activation of CD4+ and CD8+ T cells. However, utilization of mRNA molecules also has some drawbacks such as degradation by ubiquitous nucleases in vivo. Nanoparticles (NPs) are delivery platforms that carry the desired molecule, a drug or a vaccine agent, to the target cell such as antigen presenting cells in the case of vaccine development. NP platforms also protect mRNA molecules from the degradation by nucleases. Therefore, efficient mRNA vaccines can be obtained via utilization of NPs in the formulation. Although lipid-based NPs are widely preferred in vaccine development due to the nature of cell membrane, there are various types of other NPs used in vaccine formulations, such as virus-like particles (VLPs), polymers, polypeptides, dendrimers or gold NPs. Improvements in the NP delivery technologies will contribute to the development of mRNA vaccines with higher efficiency.
- adjuvant,
- delivery system,
- mRNA vaccine,
- nanoparticle,
- vaccine development,
- immune response
Citation: Sezer Okay, Öznur Özge Özcan, Mesut Karahan. Nanoparticle-based delivery platforms for mRNA vaccine development[J]. AIMS Biophysics, 2020, 7(4): 323-338. doi: 10.3934/biophy.2020023

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Abstract

Conventional vaccines have saved millions of lives, and new vaccines have also been developed; however, an urgent need for an efficient vaccine against SARS-CoV-2 showed us that vaccine development technologies should be improved more to obtain prophylactic agents rapidly during pandemic diseases. One of the next-generation vaccine technologies is utilization of mRNA molecules encoding antigens. The mRNA vaccines offer many advantages compared to conventional and other subunit vaccines. For instance, mRNA vaccines are relatively safe since they do not cause disease and mRNA does not integrate into the genome. mRNA vaccines also provide diverse types of immune responses resulting in the activation of CD4+ and CD8+ T cells. However, utilization of mRNA molecules also has some drawbacks such as degradation by ubiquitous nucleases in vivo. Nanoparticles (NPs) are delivery platforms that carry the desired molecule, a drug or a vaccine agent, to the target cell such as antigen presenting cells in the case of vaccine development. NP platforms also protect mRNA molecules from the degradation by nucleases. Therefore, efficient mRNA vaccines can be obtained via utilization of NPs in the formulation. Although lipid-based NPs are widely preferred in vaccine development due to the nature of cell membrane, there are various types of other NPs used in vaccine formulations, such as virus-like particles (VLPs), polymers, polypeptides, dendrimers or gold NPs. Improvements in the NP delivery technologies will contribute to the development of mRNA vaccines with higher efficiency.

Conflict of interest

The authors declare no conflict of interest.

References

[1]	Sharp PA (2009) The centrality of RNA. Cell 136: 577-580.
[2]	Cooper TA, Wan L, Dreyfuss G (2009) RNA and disease. Cell 136: 777-793.
[3]	Fry LE, Patrício MI, Williams J, et al. (2019) Association of messenger RNA level with phenotype in patients with choroideremia: potential implications for gene therapy dose. JAMA Ophthalmol 138: 128-135.
[4]	Li B, Zhang X, Dong Y (2019) Nanoscale platforms for messenger RNA delivery. Wires Nanomed Nanobi 11: e1530.
[5]	Midoux P, Pichon C (2015) Lipid-based mRNA vaccine delivery systems. Expert Rev Vaccines 14: 221-234.
[6]	Dannull J, Haley NR, Archer G, et al. (2013) Melanoma immunotherapy using mature DCs expressing the constitutive proteasome. J Clin Invest 123: 3135-3145.
[7]	Van Lint S, Heirman C, Thielemans K, et al. (2013) mRNA: From a chemical blueprint for protein production to an off-the-shelf therapeutic. Hum Vacc Immunother 9: 265-274.
[8]	Yang J, Arya S, Lung P, et al. (2019) Hybrid nanovaccine for the co-delivery of the mRNA antigen and adjuvant. Nanoscale 11: 21782-21789.
[9]	Le TT, Andreadakis Z, Kumar A, et al. (2020) The COVID-19 vaccine development landscape. Nat Rev Drug Discov 19: 305-306.
[10]	Geall AJ, Mandl CW, Ulmer JB (2013) RNA: the new revolution in nucleic acid vaccines. Semin Immunol 25: 152-159.
[11]	Pardi N, Hogan MJ, Porter FW, et al. (2018) mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov 17: 261-279.
[12]	Pascolo S (2015) The messenger's great message for vaccination. Expert Rev Vaccines 14: 153-156.
[13]	Deering RP, Kommareddy S, Ulmer JB, et al. (2014) Nucleic acid vaccines: prospects for non-viral delivery of mRNA vaccines. Expert Opin Drug Deliv 11: 885-899.
[14]	Liu MA (2010) Immunologic basis of vaccine vectors. Immunity 33: 504-515.
[15]	Jäschke A, Helm M (2003) RNA sex. Chem Biol 10: 1148-1150.
[16]	Pollard C, Rejman J, De Haes W, et al. (2013) Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines. Mol Ther 21: 251-259.
[17]	Vallazza B, Petri S, Poleganov MA, et al. (2015) Recombinant messenger RNA technology and its application in cancer immunotherapy, transcript replacement therapies, pluripotent stem cell induction, and beyond. Wiley Interdiscip Rev RNA 6: 471-499.
[18]	Gómez-Aguado I, Rodríguez-Castejón J, Vicente-Pascual M, et al. (2020) Nanomedicines to deliver mRNA: State of the art and future perspectives. Nanomaterials 10: 364.
[19]	Versteeg L, Almutairi MM, Hotez PJ, et al. (2019) Enlisting the mRNA vaccine platform to combat parasitic infections. Vaccines 7: 122.
[20]	Hekele A, Bertholet S, Archer J, et al. (2013) Rapidly produced SAM^® vaccine against H7N9 influenza is immunogenic in mice. Emerg Microbes Infect 2: e52.
[21]	Lindgren G, Ols S, Liang F, et al. (2017) Induction of robust B cell responses after influenza mRNA vaccination is accompanied by circulating hemagglutinin-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells. Front Immunol 8: 1539.
[22]	Luo F, Zheng L, Hu Y, et al. (2017) Induction of protective immunity against Toxoplasma gondii in mice by nucleoside triphosphate hydrolase-II (NTPase-II) self-amplifying RNA vaccine encapsulated in lipid nanoparticle (LNP). Front Microbiol 8: 605.
[23]	Michel T, Golombek S, Steinle H, et al. (2019) Efficient reduction of synthetic mRNA induced immune activation by simultaneous delivery of B18R encoding mRNA. J Biol Eng 13: 40.
[24]	Appay V, Douek DC, Price DA (2008) CD8+ T cell efficacy in vaccination and disease. Nat Med 14: 623-628.
[25]	Pardi N, Hogan MJ, Naradikian MS, et al. (2018) Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med 215: 1571-1588.
[26]	Zarghampoor F, Azarpira N, Khatami SR, et al. (2019) Improved translation efficiency of therapeutic mRNA. Gene 707: 231-238.
[27]	Kowalski PS, Rudra A, Miao L, et al. (2019) Delivering the messenger: Advances in technologies for therapeutic mRNA delivery. Mol Ther 27: 710-728.
[28]	Reichmuth AM, Oberli MA, Jaklenec A, et al. (2016) mRNA vaccine delivery using lipid nanoparticles. Ther Deliv 7: 319-334.
[29]	Lundstrom K (2009) Alphaviruses in gene therapy. Viruses 1: 13-25.
[30]	Chira S, Jackson CS, Oprea I, et al. (2015) Progresses towards safe and efficient gene therapy vectors. Oncotarget 6: 30675-30703.
[31]	Ku SH, Jo SD, Lee YK, et al. (2016) Chemical and structural modifications of RNAi therapeutics. Adv Drug Deliv Rev 104: 16-28.
[32]	Presnyak V, Alhusaini N, Chen YH, et al. (2015) Codon optimality is a major determinant of mRNA stability. Cell 160: 1111-1124.
[33]	Thess A, Grund S, Mui BL, et al. (2015) Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol Ther 23: 1456-1464.
[34]	Wojtczak BA, Sikorski PJ, Fac-Dabrowska K, et al. (2018) 5′-phosphorothiolate dinucleotide cap analogues: Reagents for messenger RNA modification and potent small-molecular inhibitors of decapping enzymes. J Am Chem Soc 140: 5987-5999.
[35]	Li B, Luo X, Dong Y (2016) Effects of chemically modified messenger RNA on protein expression. Bioconjug Chem 27: 849-853.
[36]	Li M, Zhao M, Fu Y, et al. (2016) Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways. J Control Release 228: 9-19.
[37]	Svitkin YV, Cheng YM, Chakraborty T, et al. (2017) N1-methyl-pseudouridine in mRNA enhances translation through eIF2a-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Res 45: 6023-6036.
[38]	Oberg AL, Kennedy RB, Li P, et al. (2011) Systems biology approaches to new vaccine development. Curr Opin Immunol 23: 436-443.
[39]	Auffan M, Rose J, Bottero JY, et al. (2009) Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective. Nat Nanotechnol 4: 634-641.
[40]	Treuel L, Jiang X, Nienhaus GU (2013) New views on cellular uptake and trafficking of manufactured nanoparticles. J R Soc Interface 10: 20120939.
[41]	Ulkoski D, Bak A, Wilson JT, et al. (2019) Recent advances in polymeric materials for the delivery of RNA therapeutics. Expert Opin Drug Deliv 16: 1149-1167.
[42]	Pérez-Ortín JE, Alepuz P, Chávez S, et al. (2013) Eukaryotic mRNA decay: Methodologies, pathways, and links to other stages of gene expression. J Mol Biol 425: 3750-3775.
[43]	Pati R, Shevtsov M, Sonawane A (2018) Nanoparticle vaccines against infectious diseases. Front Immunol 9: 2224.
[44]	Means TK, Hayashi F, Smith KD, et al. (2003) The Toll-like receptor 5 stimulus bacterial flagellin induces maturation and chemokine production in human dendritic cells. J Immunol 170: 5165-5175.
[45]	Boraschi D, Italiani P, Palomba R, et al. (2017) Nanoparticles and innate immunity: new perspectives on host defence. Semin Immunol 34: 33-51.
[46]	Chen YS, Hung YC, Lin WH, et al. (2010) Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide. Nanotechnology 21: 195101.
[47]	Wang T, Zou M, Jiang H, et al. (2011) Synthesis of a novel kind of carbon nanoparticle with large mesopores and macropores and its application as an oral vaccine adjuvant. Eur J Pharm Sci 44: 653-659.
[48]	Xu L, Liu Y, Chen Z, et al. (2012) Surface-engineered gold nanorods: promising DNA vaccine adjuvant for HIV-1 treatment. Nano Lett 12: 2003-2012.
[49]	Tao W, Gill HS (2015) M2e-immobilized gold nanoparticles as influenza A vaccine: role of soluble M2e and longevity of protection. Vaccine 33: 2307-2315.
[50]	Li X, Deng X, Huang Z (2001) In vitro protein release and degradation of poly-d-L-lactide-poly(ethylene glycol) microspheres with entrapped human serum albumin: quantitative evaluation of the factors involved in protein release phases. Pharm Res 18: 117-124.
[51]	Chahal JS, Fang T, Woodham AW, et al. (2017) An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model. Sci Rep 7: 252.
[52]	Chahal JS, Khan OF, Cooper CL, et al. (2016) Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci U S A 113: E4133-E4142.
[53]	Sharifnia Z, Bandehpour M, Hamishehkar H, et al. (2019) In-vitro transcribed mRNA delivery using PLGA/PEI nanoparticles into human monocyte-derived dendritic cells. Iran J Pharm Res 18: 1659-1675.
[54]	Uchida S, Kinoh H, Ishii T, et al. (2016) Systemic delivery of messenger RNA for the treatment of pancreatic cancer using polyplex nanomicelles with a cholesterol moiety. Biomaterials 82: 221-228.
[55]	Kaczmarek JC, Patel AK, Kauffman KJ, et al. (2016) Polymer-lipid nanoparticles for systemic delivery of mRNA to the lungs. Angew Chem Int Ed Engl 55: 13808-13812.
[56]	Patel AK, Kaczmarek JC, Bose S, et al. (2019) Inhaled nanoformulated mRNA polyplexes for protein production in lung epithelium. Adv Mater 31: e1805116.
[57]	Liu Y, Li Y, Keskin D, et al. (2019) Poly(β-amino esters): Synthesis, formulations, and their biomedical applications. Adv Healthc Mater 8: e1801359.
[58]	Capasso Palmiero U, Kaczmarek JC, Fenton OS, et al. (2018) Poly(β-amino ester)-co-poly(caprolactone) terpolymers as nonviral vectors for mRNA delivery in vitro and in vivo. Adv Healthc Mater 7: e1800249.
[59]	Palamà IE, Cortese B, D'Amone S, et al. (2015) mRNA delivery using non-viral PCL nanoparticles. Biomater Sci 3: 144-151.
[60]	Lacroix C, Humanes A, Coiffier C, et al. (2020) Polylactide-based reactive micelles as a robust platform for mRNA delivery. Pharm Res 37: 30.
[61]	Dong Y, Dorkin JR, Wang W, et al. (2016) Poly(glycoamidoamine) brushes formulated nanomaterials for systemic siRNA and mRNA delivery in vivo. Nano Lett 16: 842-848.
[62]	Palmerston Mendes L, Pan J, Torchilin VP (2017) Dendrimers as nanocarriers for nucleic acid and drug delivery in cancer therapy. Molecules 22: 1401.
[63]	Franiak-Pietryga I, Ziemba B, Messmer B, et al. (2018) Dendrimers as drug nanocarriers: the future of gene therapy and targeted therapies in cancer. Dendrimers: Fundamentals and Applications IntechOpen, 7.
[64]	Islam MA, Xu Y, Tao W, et al. (2018) Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA. Nat Biomed Eng 2: 850-864.
[65]	Hajam IA, Senevirathne A, Hewawaduge C, et al. (2020) Intranasally administered protein coated chitosan nanoparticles encapsulating influenza H9N2 HA2 and M2e mRNA molecules elicit protective immunity against avian influenza viruses in chickens. Vet Res 51: 37.
[66]	McCullough KC, Bassi I, Milona P, et al. (2014) Self-replicating replicon-RNA delivery to dendritic cells by chitosan-nanoparticles for translation in vitro and in vivo. Mol Ther Nucleic Acids 3: e173.
[67]	Maiyo F, Singh M (2019) Folate-targeted mRNA delivery using chitosan-functionalized selenium nanoparticles: potential in cancer immunotherapy. Pharmaceuticals (Basel) 12: 164.
[68]	Son S, Nam J, Zenkov I, et al. (2020) Sugar-nanocapsules imprinted with microbial molecular patterns for mRNA vaccination. Nano Lett 20: 1499-1509.
[69]	Siewert C, Haas H, Nawroth T, et al. (2019) Investigation of charge ratio variation in mRNA - DEAE-dextran polyplex delivery systems. Biomaterials 192: 612-620.
[70]	Zeng C, Zhang C, Walker PG, et al. (2020) Formulation and delivery technologies for mRNA vaccines. Current Topics in Microbiology and Immunology Berlin: Springer.
[71]	Scheel B, Teufel R, Probst J, et al. (2005) Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA. Eur J Immunol 35: 1557-1566.
[72]	Schlake T, Thess A, Fotin-Mleczek M, et al. (2012) Developing mRNA-vaccine technologies. RNA Biol 9: 1319-1330.
[73]	Fotin-Mleczek M, Duchardt KM, Lorenz C, et al. (2011) Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J Immunother 34: 1-15.
[74]	Schnee M, Vogel AB, Voss D, et al. (2016) An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs. PLoS Negl Trop Dis 10: e0004746.
[75]	Udhayakumar VK, De Beuckelaer A, McCaffrey J, et al. (2017) Arginine-rich peptide-based mRNA nanocomplexes efficiently instigate cytotoxic T cell immunity dependent on the amphipathic organization of the peptide. Adv Healthc Mater 6: 1601412.
[76]	Coolen AL, Lacroix C, Mercier-Gouy P, et al. (2019) Poly(lactic acid) nanoparticles and cell-penetrating peptide potentiate mRNA-based vaccine expression in dendritic cells triggering their activation. Biomaterials 195: 23-37.
[77]	Jekhmane S, De Haas R, Paulino da Silva Filho O, et al. (2017) Virus-like particles of mRNA with artificial minimal coat proteins: particle formation, stability, and transfection efficiency. Nucleic Acid Ther 27: 159-167.
[78]	Li J, Sun Y, Jia T, et al. (2014) Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer. Int J Cancer 134: 1683-1694.
[79]	Sun S, Li W, Sun Y, et al. (2011) A new RNA vaccine platform based on MS2 virus-like particles produced in saccharomyces cerevisiae. Biochem Biophys Res Commun 407: 124-128.
[80]	Zhitnyuk Y, Gee P, Lung MSY, et al. (2018) Efficient mRNA delivery system utilizing chimeric VSVG-L7Ae virus-like particles. Biochem Biophys Res Commun 505: 1097-1102.
[81]	Kauffman KJ, Webber MJ, Anderson DG (2016) Materials for non-viral intracellular delivery of messenger RNA therapeutics. J Control Release 240: 227-234.
[82]	Kulkarni JA, Cullis PR, Van Der Meel R (2018) Lipid nanoparticles enabling gene therapies: From concepts to clinical utility. Nucleic Acid Ther 28: 146-157.
[83]	Dimitriadis GJ (1978) Translation of rabbit globin mRNA introduced by liposomes into mouse lymphocytes. Nature 274: 923-924.
[84]	Moon JJ, Suh H, Bershteyn A, et al. (2011) Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat Mater 10: 243-251.
[85]	Tyagi RK, Garg NK, Sahu T (2012) Vaccination strategies against malaria: novel carrier(s) more than a tour de force. J Control Release 162: 242-254.
[86]	Adler-Moore J, Munoz M, Kim H, et al. (2011) Characterization of the murine Th2 response to immunization with liposomal M2e influenza vaccine. Vaccine 29: 4460-4468.
[87]	Monslow MA, Elbashir S, Sullivan NL, et al. (2020) Immunogenicity generated by mRNA vaccine encoding VZV gE antigen is comparable to adjuvanted subunit vaccine and better than live attenuated vaccine in nonhuman primates. Vaccine 38: 5793-5802.
[88]	Erasmus JH, Archer J, Fuerte-Stone J, et al. (2020) Intramuscular delivery of replicon RNA encoding ZIKV-117 human monoclonal antibody protects against Zika virus infection. Mol Ther Methods Clin Dev 18: 402-414.
[89]	Freyn AW, da Silva JR, Rosado VC, et al. (2020) A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice. Mol Ther 28: 1569-1584.
[90]	Lo MK, Spengler JR, Welch SR, et al. (2020) Evaluation of a single-dose nucleoside-modified messenger RNA vaccine encoding Hendra virus-soluble glycoprotein against lethal Nipah virus challenge in Syrian hamsters. J Infect Dis 221: S493-S498.
[91]	Yang T, Li C, Wang X, et al. (2020) Efficient hepatic delivery and protein expression enabled by optimized mRNA and ionizable lipid nanoparticle. Bioact Mater 5: 1053-1061.
[92]	Moyo N, Wee EG, Korber B, et al. (2020) Tetravalent immunogen assembled from conserved regions of HIV-1 and delivered as mRNA demonstrates potent preclinical T-cell immunogenicity and breadth. Vaccines (Basel) 8: 360.
[93]	Lou G, Anderluzzi G, Schmidt ST, et al. (2020) Delivery of self-amplifying mRNA vaccines by cationic lipid nanoparticles: The impact of cationic lipid selection. J Control Release 325: 370-379.
[94]	Mai Y, Guo J, Zhao Y, et al. (2020) Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity. Cell Immunol 354: 104143.
[95]	Eygeris Y, Patel S, Jozic A, et al. (2020) Deconvoluting lipid nanoparticle structure for messenger RNA delivery. Nano Lett 20: 4543-4549.
[96]	Van Hoecke L, Verbeke R, De Vlieger D, et al. (2020) mRNA encoding a bispecific single domain antibody construct protects against influenza A virus infection in mice. Mol Ther Nucleic Acids 20: 777-787.
[97]	Zhong Z, Mc Cafferty S, Combes F, et al. (2018) mRNA therapeutics deliver a hopeful message. Nano Today 23: 16-39.
[98]	Bogers WM, Oostermeijer H, Mooij P, et al. (2015) Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion. J Infect Dis 211: 947-955.
[99]	Jackson LA, Anderson EJ, Rouphael NG, et al. (2020) An mRNA vaccine against SARS-CoV-2—preliminary report. N Engl J Med . doi: 10.1056/NEJMoa2022483
[100]	Alberer M, Gnad-Vogt U, Hong HS, et al. (2017) Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet 390: 1511-1520.
[101]	Bahl K, Senn JJ, Yuzhakov O, et al. (2017) Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol Ther 25: 1316-1327.
[102]	Feldman RA, Fuhr R, Smolenov I, et al. (2019) mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37: 3326-3334.
[103]	Ding Y, Jiang Z, Saha K, et al. (2014) Gold nanoparticles for nucleic acid delivery. Mol Ther 22: 1075-1083.
[104]	Liu J, Miao L, Sui J, et al. (2020) Nanoparticle cancer vaccines: Design considerations and recent advances. Asian J Pharm Sci . doi: 10.1016/j.ajps.2019.10.006
[105]	Yeom JH, Ryou SM, Won M, et al. (2013) Inhibition of xenograft tumor growth by gold nanoparticle-DNA oligonucleotide conjugates-assisted delivery of BAX mRNA. PLoS One 8: e75369.
[106]	Azmi F, Ahmad Fuaad AAH, Skwarczynski M, et al. (2014) Recent progress in adjuvant discovery for peptide-based subunit vaccines. Hum Vaccin Immunother 10: 778-796.
[107]	Coffman RL, Sher A, Seder RA (2010) Vaccine adjuvants: Putting innate immunity to work. Immunity 33: 492-503.
[108]	Reed SG, Orr MT, Fox CB (2013) Key roles of adjuvants in modern vaccines. Nat Med 19: 1597-1608.
[109]	Oleszycka E, Lavelle EC (2014) Immunomodulatory properties of the vaccine adjuvant alum. Curr Opin Immunol 28: 1-5.
[110]	Alving CR (2009) Vaccine adjuvants. Vaccines for Biodefense and Emerging and Neglected Diseases London: Elsevier, 115-129.
[111]	Hussein WM, Liu TY, Skwarczynski M, et al. (2014) Toll-like receptor agonists: a patent review (2011–2013). Expert Opin Ther Pat 24: 453-470.
[112]	Montomoli E, Piccirella S, Khadang B, et al. (2011) Current adjuvants and new perspectives in vaccine formulation. Expert Rev Vaccines 10: 1053-1061.
[113]	Mamo T, Poland GA (2012) Nanovaccinology: The next generation of vaccines meets 21st century materials science and engineering. Vaccine 30: 6609-6611.
[114]	Banchereau J, Briere F, Caux C, et al. (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18: 767-811.
[115]	Oyewumi MO, Kumar A, Cui ZR (2010) Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Expert Rev Vaccines 9: 1095-1107.
[116]	Marasini N, Skwarczynski M, Toth I (2014) Oral delivery of nanoparticle-based vaccines. Expert Rev Vaccines 13: 1361-1376.
[117]	Kawai T, Akira S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34: 637-650.
[118]	Vasilichin VA, Tsymbal SA, Fakhardo AF, et al. (2020) Effects of metal oxide nanoparticles on Toll-like receptor mRNAs in human monocytes. Nanomaterials (Basel) 10: 127.
[119]	Roy R, Kumar D, Sharma A, et al. (2014) ZnO nanoparticles induced adjuvant effect via toll-like receptors and Src signaling in Balb/c mice. Toxicol Lett 230: 421-433.
[120]	De Temmerman M-L, Rejman J, Demeester J, et al. (2011) Particulate vaccines: on the quest for optimal delivery and immune response. Drug Discov Today 16: 569-582.
[121]	Hafner AM, Corthésy B, Merkle HP (2013) Particulate formulations for the delivery of poly(I: C) as vaccine adjuvant. Adv Drug Deliv Rev 65: 1386-1399.

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