Particulate inorganic adjuvants: Recent developments and future outlook

Journal of Pharmacy and Pharmacology

Volumn 67, Issue 3, 2015, Pages 426-449

  Maughan, Charlotte N ^a   Preston, Stephen G ^b   Williams, Gareth R ^a  

^a UNIVERSITY OF LONDON   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

adjuvant; inorganic material; particle engineering; vaccine

Indexed keywords

ALUMINUM POTASSIUM SULFATE; ANTIGEN; AS04 ADJUVANT; CALCIUM PHOSPHATE; CANCER VACCINE; COBALT DERIVATIVE; COBALT OXIDE; DNA; DNA ANTIGEN; GOLD NANOPARTICLE; HYDROXIDE; IMMUNOLOGICAL ADJUVANT; INORGANIC COMPOUND; METAL OXIDE; SILVER NANOPARTICLE; UNCLASSIFIED DRUG; VACCINE; ZINC OXIDE; ALUMINUM SULFATE; METAL;

ADAPTIVE IMMUNITY; ADSORPTION; ANTIBODY RESPONSE; CELLULAR IMMUNITY; DRUG APPROVAL; DRUG CLASSIFICATION; DRUG EFFICACY; DRUG FORMULATION; DRUG RESEARCH; DRUG SAFETY; EFFECT SIZE; FOOD AND DRUG ADMINISTRATION; IMMUNOSTIMULATION; INNATE IMMUNITY; MOLECULAR BIOLOGY; PARTICLE SIZE; PHYSICAL CHEMISTRY; REVIEW; TH2 CELL; VACCINE PRODUCTION; HUMAN; NEOPLASMS;

ADJUVANTS, IMMUNOLOGIC; ALUM COMPOUNDS; HUMANS; IMMUNITY, CELLULAR; METALS; NEOPLASMS; VACCINES;

EID: 84925750736     PISSN: 00223573     EISSN: 20427158     Source Type: Journal    
DOI: 10.1111/jphp.12352     Document Type: Review

References (170)

1. Agence French-Presse, India and 10 other Asian countries declared polio free. The Guardian, 28 March, 2014.
2. WHO. Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. p. 58, 2013.
3. NIAID. Vaccine benefits. Benefits for You and Others, 2014.
4. Rashid H, et al. Vaccination and herd immunity: what more do we know? Curr Opin Infect Dis 2012; 25: 243-249.
5. Davis MM, Bjorkman PJ,. T-cell antigen receptor genes and T-cell recognition. Nature 1988; 334: 395-402.
6. Petteri Arstila T, et al. A direct estimate of the human ab T cell receptor diversity. Science 1999; 286: 958-961.
7. Robins HS, et al. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood 2009; 114: 4099-4107.
8. Qi Q, et al. Diversity and clonal selection in the human T-cell repertoire. Proc Natl Acad Sci U S A 2014; 111: 13139-13144.
9. Schlissel MS,. Regulating antigen-receptor gene assembly. Nat Rev Immunol 2003; 3: 890-899.
10. DeFranco AL, et al. Immunity: The Immune Response in Infectious and Inflammatory Disease. Sunderland, MA: New Science Press Ltd, 2007.
11. Radbruch A, et al. Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 2006; 6: 741-750.
12. Banchereau J, Steinman RM,. Dendritic cells and the control of immunity. Nature 1998; 392: 245-252.
13. Walsh KP, Mills KH,. Dendritic cells and other innate determinants of T helper cell polarisation. Trends Immunol 2013; 34: 521-530.
14. Martinez FO, et al. Macrophage activation and polarization. Front Biosci 2008; 13: 453-461.
15. MacPherson G, Austyn J,. Exploring Immunology: Concepts and Evidence. Weinham, Germany: Wiley, 2012.
16. Ozao-Choy J, et al. Melanoma vaccines: mixed past, promising future. Surg Clin North Am 2014; 94: 1017-1030.
17. Mannie MD, Curtis AD, Tolerogenic vaccines for multiple sclerosis. Hum Vaccin Immunother 2013; 9: 1032-1038.
18. Clem AS,. Fundamentals of vaccine immunology. J Glob Infect Dis 2011; 3: 73-78.
19. Dhillon S, Curran MP,. Live attenuated measles, mumps, rubella, and varicella zoster virus vaccine (Priorix-Tetra). Paediatr Drugs 2008; 10: 337-347.
20. WHO. Polio vaccines: WHO position paper. Vol. 89, pp 73-92. January 2014.
21. NIAID. Types of vaccines. 2012. http://www.niaid.nih.gov/topics/vaccines/understanding/pages/typesvaccines.aspx.
22. Plotkin SA,. Vaccines: past, present and future. Nat Med 2005; 11 (Suppl. 4): S5-S11.
23. Aranda F, et al. Trial watch: peptide vaccines in cancer therapy. Oncoimmunol 2013; 2: e26621.
24. Saade F, Petrovsky N,. Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines 2012; 11: 189-209.
25. Moyle PM, Toth I,. Modern subunit vaccines: development, components, and research opportunities. ChemMedChem 2013; 8: 360-376.
26. Oyston P, Robinson K,. The current challenges for vaccine development. J Med Microbiol 2012; 61 (Pt 7): 889-894.
27. Pulendran B, et al. Systems vaccinology. Immunity 2010; 33: 516-529.
28. Kirby DJ, et al. Formulation and characterisation of PLGA microspheres as vaccine adjuvants. In:, Flowers DR, Perrie Y, eds. Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines, Vol. 5. New York, NY: Springer, 2013: 263-289.
29. Edelman R,. Vaccine adjuvants. Rev Infect Dis 1980; 2: 370-383.
30. Beverly PC,. Immunology of vaccination. Br Med Bull 2002; 62: 15-28.
31. Montomoli E, et al. Current adjuvants and new perspectives in vaccine formulation. Expert Rev Vaccines 2011; 10: 1053-1061.
32. FDA. Common ingredients in U.S. licensed vaccines. 2014. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm187810.htm.
33. Glenny AT, Barr M,. The precipitation of diphtheria toxoid by potash alum. J Pathol Bacteriol 1931; 34: 131-138.
34. Glenny AT, et al. The antigenic value of toxoid precipitated by potassium alum. J Pathol Bacteriol 1926; 29: 38-45.
35. Goto N, et al. Local tissue irritating effects and adjuvant activities of calcium phosphate and aluminium hydroxide with different physical properties. Vaccine 1997; 15: 1364-1371.
36. Gupta RK, Siber GR,. Adjuvants for human vaccines-current status, problems and future prospects. Vaccine 1995; 13: 1263-1276.
37. Relyveld EH, et al. Etude de la vaccination antidiphterique de sujets alergiques avec une anatoxine pure adsorbee sur phosphate de calcium. Bull WHO 1964; 30: 321-325.
38. Allan S,. Explaining alum: immunologists' dirty little secret. Nat Rev Immunol 2008; 8: 5.
39. Hem SL, et al. Preformulation studies-the next advance in aluminum adjuvant-containing vaccines. Vaccine 2010; 28: 4868-4870.
40. Heineman TC, et al. A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant. Vaccine 1999; 17: 2769-2778.
41. Exley C, et al. The immunobiology of aluminium adjuvants: how do they really work? Trends Immunol 2010; 31: 103-109.
42. Lee M, et al. Mg2+ ions reduce microglial and THP-1 cell neurotoxicity by inhibiting Ca2+ entry through purinergic channels. Brain Res 2011; 1369: 21-35.
43. HogenEsch H,. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front Immunol 2013; 3: Article no 603.
44. Hem SL, et al. Imject alum is not aluminum hydroxide adjuvant or aluminum phosphate adjuvant. Vaccine 2007; 25: 4985-4986.
45. Parks GA,. Isoelectric points of solid oxides, solid hydroxides and aqueous hydroxo complex systems. Chem Rev 1965; 65: 177-198.
46. Seeber SJ, et al. Predicting the adsorption of proteins by aluminum-containing adjuvants. Vaccine 1991; 9: 201-203.
47. Stryer L,. Biochemistry. New York: W. H. Freeman, 1981.
48. Mazur A, Harrow B,. Textbook of Biochemistry. West Washington Square Philadelphia 5, PA: Saunders, 1971.
49. Bleam WF, et al. A P-31 solid-state nuclear-magnetic-resonance study of phosphate adsorption at the boehmite aqueous-solution interface. Langmuir 1991; 7: 1702-1712.
50. Liu JC, et al. Adsorption of phosphate by aluminum hydroxycarbonate. J Pharm Sci 1984; 73: 1355-1358.
51. Lu F, et al. Control of antigen-binding to aluminum adjuvants and the immune response with a novel phosphonate linker. Vaccine 2013; 31: 4362-4367.
52. Chang M-F, et al. Degree of antigen adsorption in the vaccine or interstitial fluid and its effect on the antibody response in rabbits. Vaccine 2001; 19: 2884-2889.
53. Iyer S, et al. Relationship between the degree of antigen adsorption to aluminum hydroxide adjuvant in interstitial fluid and antibody production. Vaccine 2003; 21: 1219-1223.
54. Seeber SJ, et al. Solubilization of aluminum-containing adjuvants by constituents of interstitial fluid. J Parenter Sci Technol 1991; 45: 156-159.
55. Hansen B, et al. Relationship between the strength of antigen adsorption to an aluminum-containing adjuvant and the immune response. Vaccine 2007; 25: 6618-6624.
56. Romero Mendez IZ, et al. Potentiation of the immune response to non-adsorbed antigens by aluminum-containing adjuvants. Vaccine 2007; 25: 825-833.
57. Kanra G, et al. Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM-197 conjugate vaccine. Paediatr Int 2003; 45: 314-318.
58. Berthold I, et al. Immunogenicity in mice of anthrax recombinant protective antigen in the presence of aluminum adjuvants. Vaccine 2005; 23: 1993-1999.
59. Flebbe LM, Braley-Mullen H,. Immunopotentiating effects of the adjuvants SGP and Quil A: I. antibody responses to T-dependent and T-independent antigens. Cell Immunol 1986; 99: 119-127.
60. Gupta RK, et al. Vaccine Design: The Subunit and Adjuvant Approach. New York, NY: Plenum, 1995.
61. Watkinson A, et al. Increasing the potency of an alhydrogel-formulated anthrax vaccine by minimizing antigen-adjuvant interactions. Clin Vaccine Immunol 2013; 20: 1659-1668.
62. Egan PM, et al. Relationship between tightness of binding and immunogenicity in an aluminum-containing adjuvant-adsorbed hepatitis B vaccine. Vaccine 2009; 27: 3175-3180.
63. Peek LJ, et al. Effects of stabilizers on the destabilization of proteins upon adsorption to aluminum salt adjuvants. J Pharm Sci 2007; 96: 547-557.
64. Estey T, et al. Evaluation of chemical degradation of a trivalent recombinant protein vaccine against botulinum neurotoxin by LysC peptide mapping and MALDI-TOF mass spectrometry. J Pharm Sci 2009; 98: 2994-3012.
65. Vessely C, et al. Stability of a trivalent recombinant protein vaccine formulation against botulinum neurotoxin during storage in aqueous solution. J Pharm Sci 2009; 98: 2970-2993.
66. Clapp T, et al. Vaccines with aluminum-containing adjuvants: optimizing vaccine efficacy and thermal stability. J Pharm Sci 2011; 100: 388-401.
67. Morefield GL,. A rational, systematic approach for the development of vaccine formulations. AAPS Journal 2011; 13: 191-200.
68. Hem SL, HogenEsch H,. Relationship between physical and chemical properties of aluminum-containing adjuvants and immunopotentiation. Expert Rev Vaccines 2007; 6: 685-698.
69. Jiang D, et al. Relationship of adsorption mechanism of antigens by aluminum-containing adjuvants to in vitro elution in interstitial fluid. Vaccine 2006; 24: 1665-1669.
70. Sokolovska A, et al. Activation of dendritic cells and induction of CD4(+) T cell differentiation by aluminum-containing adjuvants. Vaccine 2007; 25: 4575-4585.
71. Gretz JE, et al. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J Exp Med 2000; 192: 1425-1439.
72. Smith DM, et al. Applications of nanotechnology for immunology. Nat Rev Immunol 2013; 13: 592-605.
73. Lanzavecchia A,. Mechanisms of antigen uptake for presentation. Curr Opin Immunol 1996; 8: 348-354.
74. Petros RA, DeSimone JM,. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov 2010; 9: 615-627.
75. Burgdorf S, et al. The mannose receptor mediates uptake of soluble but not of cell-associated antigen for cross-presentation. J Immunol 2006; 176: 6770-6776.
76. Burgdorf S, et al. Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science 2007; 316: 612-616.
77. Ghimire TR, et al. Alum increases antigen uptake, reduces antigen degradation and sustains antigen presentation by DCs in vitro. Immunol Lett 2012; 147: 55-62.
78. Harrison W,. Some observations on the use of alum precipitated diphtheria toxoid. Am J Public Health Nations Health 1935; 25: 298-300.
79. Iglesias E, et al. Influence of aluminum-based adjuvant on the immune response to multiantigenic formulation. Viral Immunol 2006; 19: 712-721.
80. Hem SL,. Elimination of aluminum adjuvants. Vaccine 2002; 20: S40-S43.
81. Hutchison S, et al. Antigen depot is not required for alum adjuvanticity. FASEB J 2012; 26: 1272-1279.
82. Kool M, et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med 2008; 205: 869-882.
83. Mosca F, et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci U S A 2008; 105: 10501-10506.
84. Wilcock LK, et al. Aluminium hydroxide down-regulates T helper 2 responses by allergen-stimulated human peripheral blood mononuclear cells. Clin Exp Allergy 2004; 34: 1373-1378.
85. Rimaniol AC, et al. In vitro interactions between macrophages and aluminum-containing adjuvants. Vaccine 2007; 25: 6784-6792.
86. Seubert A, et al. The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol 2008; 180: 5402-5412.
87. Marichal T, et al. DNA released from dying host cells mediates aluminum adjuvant activity. Nat Med 2011; 17: 996-1002.
88. Rock KL, et al. The sterile inflammatory response. Annu Rev Immunol 2010; 28: 321-342.
89. Ahrens S, et al. F-Actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 2012; 36: 635-645.
90. Zhang JG, et al. The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity 2012; 36: 646-657.
91. Flach TL, et al. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nat Med 2011; 17: 479-487.
92. Kool M, et al. Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol 2008; 181: 3755-3759.
93. Tschopp J, Schroder K,. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 2010; 10: 210-215.
94. Agostini L, et al. NALP3 forms an IL-l beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity 2004; 20: 319-325.
95. Zhang HY, et al. Processing pathway dependence of amorphous silica nanoparticle toxicity: colloidal vs pyrolytic. J Am Chem Soc 2012; 134: 15790-15804.
96. Chen CJ, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Inv 2006; 116: 2262-2271.
97. Li HF, et al. Aluminum hydroxide adjuvants activate caspase-1 and induce IL-1 beta and IL-18 release. J Immunol 2007; 178: 5271-5276.
98. Eisenbarth SC, et al. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 2008; 453: 1122-1126.
99. Li HF, et al. Cutting edge: Inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3. J Immunol 2008; 181: 17-21.
100. Kool M, et al. Alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol 2008; 181: 3755-3759.
101. Hornung V, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 2008; 9: 847-856.
102. De Gregorio E, et al. Alum adjuvanticity: unraveling a century old mystery. Eur J Immunol 2008; 38: 2068-2071.
103. McKee AS, et al. Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity. J Immunol 2009; 183: 4403-4414.
104. Franchi L, Nunez G,. The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1 beta secretion but dispensable for adjuvant activity. Eur J Immunol 2008; 38: 2085-2089.
105. Exley C,. When an aluminium adjuvant is not an aluminium adjuvant used in human vaccination programmes. Vaccine 2012; 30: 2042.
106. Cain DW, et al. Disparate adjuvant properties among three formulations of 'alum'. Vaccine 2013; 31: 653-660.
107. Kool M, et al. Alum adjuvant: some of the tricks of the oldest adjuvant. J Med Microbiol 2012; 61: 927-934.
108. Awate S, et al. Mechanisms of action of adjuvants. Front Immunol 2013; 4: Article no 114.
109. Tagliabue A, Rappuoli R,. Vaccine adjuvants: the dream becomes real. Hum Vaccin 2008; 4: 347-349.
110. Mata-Haro V, et al. The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science 2007; 316: 1628-1632.
111. Schwarz TF,. Clinical update of the AS04-adjuvanted human papillomavirus-16/18 cervical cancer vaccine, Cervarix. Adv Ther 2009; 26: 983-998.
112. Bourne N, et al. Herpes simplex virus (HSV) type 2 glycoprotein D subunit vaccines and protection against genital HSV-1 or HSV-2 disease in guinea pigs. J Infec Dis 2003; 187: 542-549.
113. Garcon N, et al. Role of AS04 in human papillomavirus vaccine: mode of action and clinical profile. Expert Opin Biol Ther 2011; 11: 667-677.
114. Garcon N, Van Mechelen M,. Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems. Expert Rev Vaccines 2011; 10: 471-486.
115. Sun BB, et al. Engineering an effective immune adjuvant by designed control of shape and crystallinity of aluminum oxyhydroxide nanoparticles. ACS Nano 2013; 7: 10834-10849.
116. Tsuchiya S, et al. Induction of maturation in cultured human monocytic leukemia-cells by a phorbol diester. Cancer Res 1982; 42: 1530-1536.
117. Li XR, et al. Aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles. J Control Release 2014; 173: 148-157.
118. Lundqvist M, et al. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci USA 2008; 105: 14265-14270.
119. Banks WA, Kastin AJ,. Aluminum-induced neurotoxicity-alterations in membrane-function at the blood-brain-barrier. Neurosci Biobehav Rev 1989; 13: 47-53.
120. Tomljenovic L,. Aluminum and Alzheimer's disease: after a century of controversy, is there a plausible link? J Alzheimers Dis 2011; 23: 567-598.
121. Chafi AH, et al. Absence of aluminum in Alzheimer's-disease brain-tissue-electron-microprobe and ion microprobe studies. Neurosci Lett 1991; 123: 61-64.
122. Landsberg JP, et al. Absence of aluminum in neuritic plaque cores in Alzheimer's-disease. Nature 1992; 360: 65-68.
123. Gherardi R, et al. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain 2001; 124: 1821-1831.
124. Gherardi RK, et al. Macrophagic myofasciitis: an emerging entity. Lancet 1998; 352: 347-352.
125. Gupta RK, et al. Adjuvant properties of aluminum and calcium compounds. In:, Powell MF, Newman MJ, ed. Vaccine Design. New York: Springer, 1995: 229-248.
126. Gupta RK, et al. Adjuvants-a balance between toxicity and adjuvanticity. Vaccine 1993; 11: 293-306.
127. WHO. WHO vaccine safety. Wkly Epidemiol Rec 1999; 74: 337-348.
128. Baylor NW, In extrinsic adjuvants in the use of allergen immunotherapy aluminium hydroxide: mechanism of action and safety assessment. 13th International Paul-Ehrlich-Seminar, Washington DC. FDA: Washington DC, 2011.
129. Goto N, et al. Studies on the toxicities of aluminum hydroxide and calcium-phosphate as immunological adjuvants for vaccines. Vaccine 1993; 11: 914-918.
130. Relyveld EH,. Preparation and use of calcium phosphate adsorbed vaccines. Dev Biol Stand 1986; 65: 131-136.
131. Aggerbeck H, Heron I,. Adjuvanticity of aluminium hydroxide and calcium phosphate in diptheria-tetanus vaccines-I. Vaccine 1995; 13: 1360-1365.
132. Aggerbeck H, et al. Booster vaccination against diptheria and tetanus in man. Comparison of calcium phosphate and aluminium hydroxide as adjuvants-II. Vaccine 1995; 13: 1366-1374.
133. Jiang DP, et al. Structure and adsorption properties of commercial calcium phosphate adjuvant. Vaccine 2004; 23: 693-698.
134. Pazar B, et al. Basic calcium phosphate crystals induce monocyte/macrophage IL-1 beta secretion through the NLRP3 inflammasome in vitro. J Immunol 2011; 186: 2495-2502.
135. Wack A, et al. Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice. Vaccine 2008; 26: 552-561.
136. He Q, et al. Calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type 2. Clin Vaccine Immunol 2002; 9: 1021-1024.
137. He Q, et al. Calcium phosphate nanoparticle adjuvant. Clin Vaccine Immunol 2000; 7: 899-903.
138. Leynadier F, et al. Immunotherapy with a calcium phosphate-adsorbed five-grass-pollen extract in seasonal rhinoconjunctivitis: a double-blind, placebo-controlled study. Clin Exp Allergy 2001; 31: 988-996.
139. Behera T, Swain P,. Antigen adsorbed calcium phosphate nanoparticles stimulate both innate and adaptive immune response in fish, Labeo rohita H. Cell Immunol 2011; 271: 350-359.
140. Volkova MA, et al. Adjuvant effects of chitosan and calcium phosphate particles in an inactivated Newcastle disease vaccine. Avian Dis 2014; 58: 46-52.
141. Olmedo H, et al. Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom. J Immunotoxicol 2014; 11: 44-49.
142. Joyappa DH, et al. Calcium phosphate nanoparticle prepared with foot and mouth disease virus P1-3CD gene construct protects mice and guinea pigs against the challenge virus. Vet Microbiol 2009; 139: 58-66.
143. Zhou W, et al. Just-in-time vaccines: biomineralized calcium phosphate core-immunogen shell nanoparticles induce long-lasting CD8(+) T cell responses in mice. Nanomedicine 2014; 10: 571-578.
144. Jones S, et al. Protein coated microcrystals formulated with model antigens and modified with calcium phosphate exhibit enhanced phagocytosis and immunogenicity. Vaccine 2013; 32: 4234-4242.
145. Wang X, et al. Zn- and Mg- containing tricalcium phosphates-based adjuvants for cancer immunotherapy. Sci Rep 2013; 3: Article no 2203.
146. Kozlova D, et al. Calcium phosphate nanoparticles show an effective activation of the innate immune response in vitro and in vivo after functionalization with flagellin. Virol Sin 2014; 29: 33-39.
147. Lee DD, Aiolova M, US patent application US 09/153,133: calcium phosphate delivery vehicle and adjuvant. 2003. Brookline, MA (US), Patent Application.
148. Roy R, et al. Zinc oxide nanoparticles provide an adjuvant effect to ovalbumin via a Th2 response in Balb/c mice. Int Immunol 2014; 26: 159-172.
149. Matsumura M, et al. Adjuvant effect of zinc oxide on Th2 but not Th1 immune responses in mice. Immunopharmacol Immunotoxicol 2010; 32: 56-62.
150. Winchurch RA, et al. Supplemental zinc (Zn2+) restores antibody formation in cultures of aged spleen cells: effects on mediator production. Eur J Immunol 1987; 17: 127-132.
151. Cho WS, et al. Adjuvanticity and toxicity of cobalt oxide nanoparticles as an alternative vaccine adjuvant. Nanomedicine 2012; 7: 1495-1505.
152. Cho WS, et al. NiO and Co3O4 nanoparticles induce lung DTH-like responses and alveolar lipoproteinosis. Eur Respir J 2012; 39: 546-557.
153. Naim JO, et al. Mechanisms of adjuvancy: I-metal oxides as adjuvants. Vaccine 1997; 15: 1183-1193.
154. Wang X, et al. Pore size-dependent immunogenic activity of mesoporous silica-based adjuvants in cancer immunotherapy. J Biomed Mater Res A 2014; 102: 967-974.
155. Wang X, et al. Particle-size-dependent toxicity and immunogenic activity of mesoporous silica-based adjuvants for tumor immunotherapy. Acta Biomater 2013; 9: 7480-7489.
156. Li A, et al. Signalling pathways involved in the activation of dendritic cells by layered double hydroxide nanoparticles. Biomater 2010; 31: 748-756.
157. Li A, et al. The use of layered double hydroxides as DNA vaccine delivery vector for enhancement of anti-melanoma immune response. Biomater 2011; 32: 469-477.
158. Wang J, et al. The enhanced immune response of hepatitis B virus DNA vaccine using SiO2@LDH nanoparticles as an adjuvant. Biomater 2014; 35: 466-478.
159. Williams GR, et al. Immunity induced by a broad class of inorganic crystalline materials is directly controlled by their chemistry. J Exp Med 2014; 211: 1019-1025.
160. Bastús NG, et al. Peptides conjugated to gold nanoparticles induce macrophage activation. Mol Immunol 2009; 46: 743-748.
161. Wang Y-T, et al. The use of a gold nanoparticle-based adjuvant to improve the therapeutic efficacy of hNgR-Fc protein immunization in spinal cord-injured rats. Biomater 2011; 32: 7988-7998.
162. Chen YS, et al. Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide. Nanotechnol 2010; 21: 195101.
163. Xu LG, et al. Surface-engineered gold nanorods: promising DNA vaccine adjuvant for HIV-1 treatment. Nano Lett 2012; 12: 2003-2012.
164. Parween S, et al. Induction of humoral immune response against PfMSP-1(19) and PvMSP-1(19) using gold nanoparticles along with alum. Vaccine 2011; 29: 2451-2460.
165. Tao W, et al. Gold nanoparticle-M2e conjugate coformulated with CpG induces protective immunity against influenza A virus. Nanomedicine 2014; 9: 237-251.
166. Wei M, et al. Polyvalent immunostimulatory nanoagents with self-assembled CpG oligonucleotide-conjugated gold nanoparticles. Angew Chem Int Ed Engl 2012; 51: 1202-1206.
167. Tsai CY, et al. Size-dependent attenuation of TLR9 signaling by gold nanoparticles in macrophages. J Immunol 2012; 188: 68-76.
168. Niikura K, 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: 3926-3938.
169. Martinez-Gutierrez F, et al. Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanomedicine 2012; 8: 328-336.
170. Xu YY, et al. Evaluation of the adjuvant effect of silver nanoparticles both in vitro and in vivo. Toxicol Lett 2013; 219: 42-48.