Nasal and pulmonary vaccine delivery using particulate carriers

Expert Opinion on Drug Delivery

Volumn 12, Issue 6, 2015, Pages 993-1008

  Jia, Yimei ^a   Krishnan, Lakshmi ^a   Omri, Abdelwahab ^b  

^a NATIONAL RESEARCH COUNCIL CANADA   (Canada)

^b LAURENTIAN UNIVERSITY   (Canada)

Author keywords

Adjuvant; Formulation; Immunogenicity; Particles; Particulate carrier systems; Pulmonary delivery; Respiratory infections; Vaccines

Indexed keywords

BCG VACCINE; CHEMOKINE RECEPTOR CCR7; CHICKENPOX MEASLES MUMPS RUBELLA VACCINE; CHITOSAN NANOPARTICLE; CHOLERA TOXIN; DIPHTHERIA PERTUSSIS POLIOMYELITIS TETANUS HAEMOPHILUS INFLUENZAE TYPE B VACCINE; DIPHTHERIA PERTUSSIS TETANUS VACCINE; DIPHTHERIA VACCINE; DNA VACCINE; GAMMA INTERFERON; GOLD NANOPARTICLE; HAEMOPHILUS INFLUENZAE TYPE B VACCINE; INFLUENZA VACCINE; INTERLEUKIN 12; INTERLEUKIN 18; INTERLEUKIN 2; ISCOM; LIPOSOME; MACROGOL; MEASLES MUMPS RUBELLA VACCINE; MEASLES VACCINE; PNEUMOCOCCUS VACCINE; POLYETHYLENEIMINE; POLYLACTIC ACID; POLYMER; SEVERE ACUTE RESPIRATORY SYNDROME VACCINE; TUMOR NECROSIS FACTOR ALPHA; VACCINE; VIROSOME; ANTIGEN; IMMUNOLOGICAL ADJUVANT;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CROSS PRESENTATION; DRY POWDER; HAEMOPHILUS INFECTION; HUMAN; INFLUENZA; INFLUENZA A (H5N1); INHALATION; INNATE IMMUNITY; MEASLES; MUCOSAL IMMUNITY; NANOEMULSION; NONHUMAN; PERTUSSIS; PNEUMOCOCCAL INFECTION; RESPIRATORY TRACT INFECTION; REVIEW; SEVERE ACUTE RESPIRATORY SYNDROME; T LYMPHOCYTE; TUBERCULOSIS; VACCINATION; VIRUS LIKE AGENT; ANIMAL; DRUG DELIVERY SYSTEM; IMMUNOLOGY; LUNG; NOSE MUCOSA; RESPIRATORY TRACT MUCOSA;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANTIGENS; DRUG DELIVERY SYSTEMS; HUMANS; IMMUNITY, MUCOSAL; LUNG; NASAL MUCOSA; RESPIRATORY MUCOSA; VACCINATION; VACCINES;

EID: 84929749498     PISSN: 17425247     EISSN: 17447593     Source Type: Journal    
DOI: 10.1517/17425247.2015.1044435     Document Type: Review

References (125)

1. Dasaraju P, Chien L. Medical microbiology. 4th edition. Chapter 93. Infections of the Respiratory System, Galveston, Texas; 1996
2. Louie JK, Hacker JK, Gonzales R, et al. Characterization of viral agents causing acute respiratory infection in a San Francisco University Medical Center Clinic during the influenza season. Clin Infect Dis 2005;41:822-8
3. Global Challenges/Chemistry Solutions. Promoting public health: Saving lives with the first dry powder inhalable vaccine for measles ACS press room news. Available from: http://www.acs.org/content/acs/en/pressroom/podcasts/globalchallenges/publichealth/vaccine-formeasles-podcast-page.html [Last accessed 20 November 2009]
4. Yoshikawa TT. Epidemiology and unique aspects of aging and infectious diseases. Clin Infect Dis 2000;30:931-3
5. McElhaney JE. Prevention of infectious diseases in older adults through immunization: the challenge of the senescent immune response. Expert Rev Vaccines 2009;8:593-606
6. Holmgren J, Svennerholm AM. Vaccines against mucosal infections. Curr Opin Immunol 2012;24:343-53
7. Neutra MR, Kozlowski PA. Mucosal vaccines: the promise and the challenge. Nat Rev Immunol 2006;6:148-58
8. Ozeki T, Tagami T. Drug/polymer nanoparticles prepared using unique spray nozzles and recent progress of inhaled formulation. Asian J Pharma Sci 2014;9:236-43
9. Kunda NK, Somavarapu S, Gordon SB, et al. Nanocarriers targeting dendritic cells for pulmonary vaccine delivery. Pharma Res 2013;30:325-41
10. Mathias NR, Hussain MA. Non-invasive systemic drug delivery: developability considerations for alternate routes of administration. J Pharma Sci 2009;99:1-20
11. Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 2003;56:588-99
12. Li W, Deng G, Li M, et al. Roles of Mucosal Immunity against Mycobacterium tuberculosis Infection. Tuberc Res Treat 2012;2012:791728
13. Gomez MI, Prince A. Airway epithelial cell signaling in response to bacterial pathogens. Pediatr Pulmonol 2008;43:11-19
14. Lehrer RI. Primate defensins. Nat Rev Microbiol 2004;2:727-38
15. Martin TR, Frevert CW. Innate immunity in the lungs. Proc Am Thorac Soc 2005;2:403-11
16. Martin TR, Rubenfeld GD, Ruzinski JT, et al. Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 1997;155:937-44
17. Vu Q, McCarthy KM, McCormack JM, et al. Lung dendritic cells are primed by inhaled particulate antigens, and retain MHC class II/antigenic peptide complexes in hilar lymph nodes for a prolonged period of time. Immunology 2002;105:488-98
18. Merrill WW, Naegel GP, Matthay RA, et al. Production of chemotactic factor(s) by in vivo cultured human alveolar macrophages. Chest 1979;75:224
19. Shikina T, Hiroi T, Iwatani K, et al. IgA class switch occurs in the organized nasopharynx-And gut-Associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut. J Immunol 2004;172:6259-64
20. Ogra PL. Mucosal immunity: some historical perspective on host-pathogen interactions and implications for mucosal vaccines. Immunol Cell Biol 2003;81:23-33
21. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Ann Rev Immunol 2000;18:767-811
22. Vareille M, Kieninger E, Edwards MR, et al. The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev 2011;24:210-29
23. Saeki H, Moore AM, Brown MJ, et al. Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J Immunol 1999; 162:2472-5
24. Davidson S, Crotta S, McCabe TM, et al. Pathogenic potential of interferon alphabeta in acute influenza infection. Nat Commun 2014;5:3864
25. Curtis JL. Cell-mediated adaptive immune defense of the lungs. Proc Am Thorac Soc 2005;2:412-16
26. Nair S, Bayer W, Ploquin MJ, et al. Distinct roles of CD4+ T cell subpopulations in retroviral immunity: lessons from the Friend virus mouse model. Retrovirology 2011;8:1-12
27. Nagamachi M, Sakata D, Kabashima K, et al. Facilitation of Th1-mediated immune response by prostaglandin E receptor EP1. J Exp Med 2007;204:2865-74
28. Wiley JA, Cerwenka A, Harkema JR, et al. Production of interferon-gamma by influenza hemagglutinin-specific CD8 effector T cells influences the development of pulmonary immunopathology. Am J Pathol 2001;158:119-30
29. Hufford MM, Kim TS, Sun J, et al. Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. J Exp Med 2011;208:167-80
30. Hodge LM, Simecka JW. Role of upper and lower respiratory tract immunity in resistance to Mycoplasma respiratory disease. J Infect Dis 2002;186:290-4
31. Woolard MD, Hodge LM, Jones HP, et al. The upper and lower respiratory tracts differ in their requirement of IFN-gamma and IL-4 in controlling respiratory mycoplasma infection and disease. J Immunol 2004; 172:6875-83
32. Rueckert C, Guzman CA. Vaccines: from empirical development to rational design. PLoS Pathog 2012;8:e1003001
33. De Souza Reboucas J, Esparza I, Ferrer M, et al. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy. J Biomed Biotechnol 2012;2012:474605
34. Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol 2013;4:114-54
35. Burrell LS, White JL, Hem SL. Stability of aluminium-containing adjuvants during aging at room temperature. Vaccine 2000;18:2188-92
36. Seubert A, Monaci E, Pizza M, et al. The adjuvants aluminum hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. J Immunol 2008;180:5402-12
37. Sun H, Pollock KG, Brewer JM. Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro. Vaccine 2003;21:849-55
38. Morel S, Didierlaurent A, Bourguignon P, et al. Adjuvant System AS03 containing alpha-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine 2011;29:2461-73
39. Calabro S, Tortoli M, Baudner BC, et al. Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine 2011;29:1812-23
40. Thomas C, Gupta V, Ahsan F. Particle size influences the immune response produced by hepatitis B vaccine formulated in inhalable particles. Pharm Res 2010;27:905-19
41. Vila A, Sanchez A, Evora C, et al. PLA-PEG particles as nasal protein carriers: the influence of the particle size. Int J Pharm 2005;292:43-52
42. Xiang SD, Scholzen A, Minigo G, et al. Pathogen recognition and development of particulate vaccines: does size matter? Methods 2006;40:1-9
43. Romoren K, Fjeld XT, Poleo AB, et al. Transfection efficiency and cytotoxicity of cationic liposomes in primary cultures of rainbow trout (Oncorhynchus mykiss) gill cells. Biochim Biophys Acta 2005;1717:50-7
44. Aguilar JC, Rodriguez EG. Vaccine adjuvants revisited. Vaccine 2007;25:3752-62
45. Moyle PM, McGeary RP, Blanchfield JT, et al. Mucosal immunisation: Adjuvants and delivery systems. Curr Drug Deliv 2004;1: 385-96
46. de Haan A, Groen G, Prop J, et al. Mucosal immunoadjuvant activity of liposomes: role of alveolar macrophages. Immunology 1996;89:488-93
47. Vujanic A, Sutton P, Snibson KJ, et al. Mucosal vaccination: lung versus nose. Vet Immunol Immunopathol 2011;148:172-7
48. Tamura S, Yamanaka A, Shimohara M, et al. Synergistic action of cholera toxin B subunit (and Escherichia coli heatlabile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine. Vaccine 1994;12:419-26
49. Lu D, Hickey AJ. Pulmonary vaccine delivery. Expert Rev Vaccines 2007;6:213-26
50. Yamamoto M, Briles DE, Yamamoto S, et al. A nontoxic adjuvant for mucosal immunity to pneumococcal surface protein A. J Immunol 1998;161: 4115-21
51. Eriksson K, Holmgren J. Recent advances in mucosal vaccines and adjuvants. Curr Opin Immunol 2002;14:666-72
52. Fu J, Liang J, Kang H, et al. Effects of different CpG oligodeoxynucleotides with inactivated avian H5N1 influenza virus on mucosal immunity of chickens. Poultry Sci 2013;92:2866-75
53. Staats HF, Bradney CP, Gwinn WM, et al. Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization. J Immunol 2001;167:5386-94
54. Eo SK, Lee S, Kumaraguru U, et al. Immunopotentiation of DNA vaccine against herpes simplex virus via codelivery of plasmid DNA expressing CCR7 ligands. Vaccine 2001;19:4685-93
55. Baca-Estrada ME, Foldvari M, Babiuk SL, et al. Vaccine delivery: lipidbased delivery systems. J Biotechnol 2000;83:91-104
56. Therien HM, Shahum E. Importance of physical association between antigen and liposomes in liposomes adjuvanticity. Immunol Lett 1989;22:253-8
57. Ingvarsson PT, Rasmussen IS, Viaene M, et al. The surface charge of liposomal adjuvants is decisive for their interactions with the Calu-3 and A549 airway epithelial cell culture models. Eur J Pharma Biopharma 2014;87:480-8
58. Foged C, Arigita C, Sundblad A, et al. Interaction of dendritic cells with antigen-containing liposomes: effect of bilayer composition. Vaccine 2004;22:1903-13
59. Lopes LM, Chain BM. Liposome-mediated delivery stimulates a class I-restricted cytotoxic T cell response to soluble antigen. Eur J Immunol 1992;22:287-90
60. Okada E, Sasaki S, Ishii N, et al. Intranasal immunization of a DNA vaccine with IL-12-And granulocyte-macrophage colonystimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. J Immunol 1997;159:3638-47
61. Wang D, Christopher ME, Nagata LP, et al. Intranasal immunization with liposome-encapsulated plasmid DNA encoding influenza virus hemagglutinin elicits mucosal, cellular and humoral immune responses. J Clin Virol 2004;31(Suppl 1):S99-106
62. Lovgren K, Kaberg H, Morein B. An experimental influenza subunit vaccine (iscom): induction of protective immunity to challenge infection in mice after intranasal or subcutaneous administration. Clin Exp Immunol 1990;82:435-9
63. Shewen PE, Carrasco-Medina L, McBey BA, et al. Challenges in mucosal vaccination of cattle. Vet Immunol Immunopathol 2009;128:192-8
64. Abusugra I, Morein B. Iscom is an efficient mucosal delivery system for Mycoplasma mycoides subsp. mycoides (MmmSC) antigens inducing high mucosal and systemic antibody responses. FEMS Immunol Med Microbiol 1999;23:5-12
65. Coulter A, Harris R, Davis R, et al. Intranasal vaccination with ISCOMATRIX adjuvanted influenza vaccine. Vaccine 2003;21:946-9
66. Krishnan L, Sprott GD. Archaeosome adjuvants: immunological capabilities and mechanism(s) of action. Vaccine 2008;26:2043-55
67. Patel GB, Zhou H, Ponce A, et al. Mucosal and systemic immune responses by intranasal immunization using archaeal lipid-Adjuvanted vaccines. Vaccine 2007;25:8622-36
68. Patel GB, Zhou H, Ponce A, et al. Intranasal immunization with an archaeal lipid mucosal vaccine adjuvant and delivery formulation protects against a respiratory pathogen challenge. PLoS One 2010;5:e15574
69. Kushnir N, Streatfield SJ, Yusibov V. Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development. Vaccine 2012;31:58-83
70. Roldao A, Mellado MC, Castilho LR, et al. Virus-like particles in vaccine development. Expert Rev Vaccines 2010;9:1149-76
71. Ruedl C, Schwarz K, Jegerlehner A, et al. Virus-like particles as carriers for T-cell epitopes: limited inhibition of T-cell priming by carrier-specific antibodies. J Virol 2005;79:717-24
72. Lo-Man R, Rueda P, Sedlik C, et al. A recombinant virus-like particle system derived from parvovirus as an efficient antigen carrier to elicit a polarized Th1 immune response without adjuvant. Eur J Immunol 1998;28:1401-7
73. Ye L, Wen Z, Dong K, et al. Immunization with a Mixture of HIV Env DNA and VLP Vaccines Augments Induction of CD8 T Cell Responses. J Biomed Biotechnol 2010;2010:497219
74. Velasquez LS, Hjelm BE, Arntzen CJ, et al. An intranasally delivered Toll-like receptor 7 agonist elicits robust systemic and mucosal responses to Norwalk viruslike particles. Clin Vaccine Immunol 2010;17:1850-8
75. Gluck R, Mischler R, Durrer P, et al. Safety and immunogenicity of intranasally administered inactivated trivalent virosome-formulated influenza vaccine containing Escherichia coli heatlabile toxin as a mucosal adjuvant. J Infect Dis 2000;181:1129-32
76. Perrone LA, Ahmad A, Veguilla V, et al. Intranasal vaccination with 1918 influenza virus-like particles protects mice and ferrets from lethal 1918 and H5N1 influenza virus challenge. J Virol 2009;83:5726-34
77. Herbst-Kralovetz M, Mason HS, Chen Q. Norwalk virus-like particles as vaccines. Expert Rev Vaccines 2010;9:299-307
78. Guerrero RA, Ball JM, Krater SS, et al. Recombinant Norwalk virus-like particles administered intranasally to mice induce systemic and mucosal (fecal and vaginal) immune responses. J Virol 2001;75:9713-22
79. Lambkin R, Oxford JS, Bossuyt S, et al. Strong local and systemic protective immunity induced in the ferret model by an intranasal virosome-formulated influenza subunit vaccine. Vaccine 2004;22:4390-6
80. Fiers W, De Filette M, El Bakkouri K, et al. M2e-based universal influenza A vaccine. Vaccine 2009;27:6280-3
81. Schotsaert M, De Filette M, Fiers W, et al. Universal M2 ectodomain-based influenza A vaccines: preclinical and clinical developments. Expert Rev Vaccines 2009;8:499-508
82. Csaba N, Garcia-Fuentes M, Alonso MJ. Nanoparticles for nasal vaccination. Adv Drug Deliv Rev 2009;61:140-57
83. Mansour HM, Sohn M, Al-Ghananeem A, et al. Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects. Int J Mol Sci 2010;11:3298-322
84. Tamber H, Johansen P, Merkle HP, et al. Formulation aspects of biodegradable polymeric microspheres for antigen delivery. Adv Drug Del Rev 2005;57:357-76
85. Slutter B, Bal S, Keijzer C, et al. Nasal vaccination with N-trimethyl chitosan and PLGA based nanoparticles: nanoparticle characteristics determine quality and strength of the antibody response in mice against the encapsulated antigen. Vaccine 2010;28:6282-91
86. Vila A, Sanchez A, Evora C, et al. PEG-PLA nanoparticles as carriers for nasal vaccine delivery. J Aerosol Med 2004;17:174-85
87. Jung T, Kamm W, Breitenbach A, et al. Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graftpoly( lactide-co-glycolide): evaluation of antibody response after oral and nasal application in mice. Pharma Res 2001;18:352-60
88. Illum L, Jabbal-Gill I, Hinchcliffe M, et al. Chitosan as a novel nasal delivery system for vaccines. Adv Drug Del Rev 2001;51:81-96
89. Vila A, Sanchez A, Tobio M, et al. Design of biodegradable particles for protein delivery. J Control Release 2002;78:15-24
90. Bivas-Benita M, Lin MY, Bal SM, et al. Pulmonary delivery of DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c associated to PLGA-PEI nanoparticles enhances T cell responses in a DNA prime/protein boost vaccination regimen in mice. Vaccine 2009;27:4010-17
91. Son S, Kim WJ. Biodegradable nanoparticles modified by branched polyethylenimine for plasmid DNA delivery. Biomaterials 2009;31:133-43
92. 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 2012;21:149-57
93. Shim BS, Park SM, Quan JS, et al. Intranasal immunization with plasmid DNA encoding spike protein of SARScoronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses. BMC Immunol 2011;11:65
94. Regnstrom K, Ragnarsson EG, Koping-Hoggard M, et al. PEI -A potent, but not harmless, mucosal immuno-stimulator of mixed T-helper cell response and FasL-mediated cell death in mice. Gene Ther 2003;10:1575-83
95. Torrieri-Dramard L, Lambrecht B, Ferreira HL, et al. Intranasal DNA vaccination induces potent mucosal and systemic immune responses and cross-protective immunity against influenza viruses. Mol Ther 2010;19:602-11
96. Davies LA, McLachlan G, Sumner-Jones SG, et al. Enhanced lung gene expression after aerosol delivery of concentrated pDNA/PEI complexes. Mol Ther 2008;16:1283-90
97. Mann JF, McKay PF, Arokiasamy S, et al. Pulmonary delivery of DNA vaccine constructs using deacylated PEI elicits immune responses and protects against viral challenge infection. J Control Release 2013;170:452-9
98. Dodane V, Amin Khan M, Merwin JR. Effect of chitosan on epithelial permeability and structure. Int J Pharm 1999;182:21-32
99. van der Lubben IM, Kersten G, Fretz MM, et al. Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine 2003;21:1400-8
100. Alpar HO, Somavarapu S, Atuah KN, et al. Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery. Adv Drug Del Rev 2005;57:411-30
101. Kang ML, Jiang HL, Kang SG, et al. Pluronic F127 enhances the effect as an adjuvant of chitosan microspheres in the intranasal delivery of Bordetella bronchiseptica antigens containing dermonecrotoxin. Vaccine 2007;25:4602-10
102. Moingeon P, de Taisne C, Almond J. Delivery technologies for human vaccines. Br Med Bull 2002;62:29-44
103. Jin T, Tsao E. Powder vaccines for pulmonary delivery. Springer, New York; 2012
104. Nandiyanto A, Okuyama K. Progress in developing spray-drying methods for the production of controlled morphology particles: From the nanometer to submicrometer size ranges. Adv Powder Tech 2011;2:1-19
105. Sou T, Meeusen EN, de Veer M, et al. New developments in dry powder pulmonary vaccine delivery. Trends Biotechnol 2011;29:191-8
106. Garcia-Contreras L, Wong YL, Muttil P, et al. Immunization by a bacterial aerosol. Proc Nat Acad Sci USA 2008;105:4656-60
107. Zhao L, Seth A, Wibowo N, et al. Nanoparticle vaccines. Vaccine 2013;32:327-37
108. Thakur N, Garg G, Sharma PK, et al. Nanoemulsions: A Review on Various Pharmaceutical Application. Global J Pharma 2012;6:222-5
109. Wong PT, Wang SH, Ciotti S, et al. Formulation and characterization of nanoemulsion intranasal adjuvants: effects of surfactant composition on mucoadhesion and immunogenicity. Mol Pharm 2013;11:531-44
110. Bielinska AU, Janczak KW, Landers JJ, et al. Nasal immunization with a recombinant HIV gp120 and nanoemulsion adjuvant produces Th1 polarized responses and neutralizing antibodies to primary HIV type 1 isolates. AIDS Res Hum Retroviruses 2008;24:271-81
111. Kalkanidis M, Pietersz GA, Xiang SD, et al. Methods for nano-particle based vaccine formulation and evaluation of their immunogenicity. Methods 2006;40:20-9
112. Tao W, Ziemer KS, Gill HS. Gold nanoparticle-M2e conjugate coformulated with CpG induces protective immunity against influenza A virus. Nanomedicine (Lond) 2013;9:237-51
113. Sharma S, Mukkur TK, Benson HA, et al. Pharmaceutical aspects of intranasal delivery of vaccines using particulate systems. J Pharm Sci 2009;98:812-43
114. Mielcarek N, Alonso S, Locht C. Nasal vaccination using live bacterial vectors. Adv Drug Del Rev 2001;51:55-69
115. Harokopakis E, Hajishengallis G, Greenway TE, et al. Mucosal immunogenicity of a recombinant Salmonella typhimurium-cloned heterologous antigen in the absence or presence of coexpressed cholera toxin A2 and B subunits. Infect Immun 1997;65:1445-54
116. Kohlmann R, Schwannecke S, Tippler B, et al. Protective efficacy and immunogenicity of an adenoviral vector vaccine encoding the codon-optimized F protein of respiratory syncytial virus. J Virol 2009;83:12601-10
117. Gao W, Soloff AC, Lu X, et al. Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization. J Virol 2006;80:1959-64
118. Pandey A, Singh N, Vemula SV, et al. Impact of preexisting adenovirus vector immunity on immunogenicity and protection conferred with an adenovirusbased H5N1 influenza vaccine. PLoS One 2012;7:e33428
119. Kumar U, Kumar S, Varghese S, et al. DNA vaccine: A modern biotechnological approach towards human welfare and clinical trials. Int J Res Biomed Biotechnol 2013;3:17-20
120. Saade F, Petrovsky N. Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines 2012;11:189-209
121. Vajdy M, Srivastava I, Polo J, et al. Mucosal adjuvants and delivery systems for protein-, DNA-And RNA-based vaccines. Immunol Cell Biol 2004;82:617-27
122. Torrieri-Dramard L, Lambrecht B, Ferreira HL, et al. Intranasal DNA vaccination induces potent mucosal and systemic immune responses and cross-protective immunity against influenza viruses. Mol Ther 2011;19:602-11
123. Rosada RS, de la Torre LG, Frantz FG, et al. Protection against tuberculosis by a single intranasal administration of DNAhsp65 vaccine complexed with cationic liposomes. BMC Immunol 2008;9:38
124. Yang ZY, Kong WP, Huang Y, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 2004;428:561-4
125. Complete List of Vaccines Licensed for Immunization and Distribution in the US. US Food and Drug Administration, Consumer Affairs Branch (CBER). Silver Spring, MD. Available from: www. fda gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM093833 [Last accessed 29 January 2015]