Mucosal delivery of vaccine antigens and its advantages in pediatrics

Advanced Drug Delivery Reviews

Volumn 58, Issue 1, 2006, Pages 52-67

  De Magistris, Maria Teresa ^a  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

Author keywords

Adjuvants; Delivery systems; Mechanism of action of adjuvants; Mucosal immune system; Mucosal vaccines; Pediatric vaccines; Vaccines

Indexed keywords

IMMUNIZATION; IMMUNOLOGY; MICROORGANISMS; PATHOLOGY; VACCINES;

ADJUVANTS; DELIVERY SYSTEMS; MECHANISM OF ACTION OF ADJUVANTS; MUCOSAL IMMUNE SYSTEM; MUCOSAL VACCINES; PEDIATRIC VACCINES;

PEDIATRICS;

ADENOVIRUS VECTOR; BACTERIAL TOXIN; BIOPOLYMER; CANCER VACCINE; CHITOSAN; CHOLERA TOXIN; CLOSTRIDIUM DIFFICILE TOXIN A; CPG OLIGODEOXYNUCLEOTIDE; CYTOKINE; DEFENSIN; DNA VACCINE; ESCHERICHIA COLI ENTEROTOXIN; FRAGILYSIN; HEPATITIS A VACCINE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; HYBRID PROTEIN; IMMUNOLOGICAL ADJUVANT; INFLUENZA VACCINE; ISCOM; LIPOSOME; PERTUSSIS TOXIN; PHOSPHORYL LIPID A; POLYGLACTIN; POLYSACCHARIDE; PSEUDOMONAS EXOTOXIN; QS 21; QUIL A; SAPONIN; UNINDEXED DRUG; VACCINE; VIROSOME; VIRUS VECTOR;

ACTIVE IMMUNIZATION; ANTIGEN PURIFICATION; CLINICAL TRIAL; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG FORMULATION; DRUG PURIFICATION; DRUG SAFETY; DRUG SOLUBILITY; HEPATITIS A; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOGENICITY; IMMUNOSTIMULATION; INFECTION PREVENTION; INFLUENZA; MUCOSAL IMMUNITY; NON INVASIVE PROCEDURE; NONHUMAN; PEDIATRICS; PRIORITY JOURNAL; REVIEW; SEXUALLY TRANSMITTED DISEASE; TISSUE INJURY; VACCINATION REACTION; VIRUS INFECTION; VIRUS PARTICLE; VIRUS PATHOGENESIS;

ADJUVANTS, IMMUNOLOGIC; ANTIGENS; CHILD; DRUG DELIVERY SYSTEMS; HUMANS; IMMUNITY, MUCOSAL; VACCINES;

EID: 33645821879     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2006.01.002     Document Type: Review

References (147)

1. McGhee J.R., Mestecky J., Dertzbaugh M.T., Eldridge J.H., Hirasawa M., and Kiyono H. The mucosal immune system: from fundamental concepts to vaccine development. Vaccine 10 (1992) 75-88
2. Holmgren J., and Czerkinsky C. Mucosal immunity and vaccines. Nat. Med. 11 (2005) S45-S53
3. Miyoshi J., and Takai Y. Molecular perspective on tight-junction assembly and epithelial polarity. Adv. Drug Deliv. Rev. 57 (2005) 815-855
4. Neutra M.R., Frey A., and Kraehenbuhl J.P. Epithelial M cells: gateways for mucosal infection and immunization. Cell 86 (1996) 345-348
5. Nagler-Anderson C. Man the barrier! Strategic defences in the intestinal mucosa. Nat. Rev. Immunol. 1 (2001) 59-67
6. Rescigno M., Urbano M., Valzasina B., Francolini M., Rotta G., Bonasio R., Granucci F., Kraehenbuhl J.P., and Ricciardi-Castagnoli P. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2 (2001) 361-367
7. Niess J.H., Brand S., Gu X., Landsman L., Jung S., McCormick B.A., Vyas J.M., Boes M., Ploegh H.L., Fox J.G., Littman D.R., and Reinecker H.C. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307 (2005) 254-258
8. Neutra M.R., Pringault E., and Kraehenbuhl J.P. Antigen sampling across epithelial barriers and induction of mucosal immune responses. Annu. Rev. Immunol. 14 (1996) 275-300
9. Kiyono H., and Fukuyama S. NALT- versus Peyer's-patch-mediated mucosal immunity. Nat. Rev. Immunol. 4 (2004) 699-710
10. Cheroutre H., and Madakamutil L. Acquired and natural memory T cells join forces at the mucosal front line. Nat. Rev. Immunol. 4 (2004) 290-300
11. Rojas R., and Apodaca G. Immunoglobulin transport across polarized epithelial cells. Nat. Rev., Mol. Cell Biol. 3 (2002) 944-955
12. Fagarasan S., and Honjo T. Intestinal IgA synthesis: regulation of front-line body defences. Nat. Rev. Immunol. 3 (2003) 63-72
13. Phalipon A., Cardona A., Kraehenbuhl J.P., Edelman L., Sansonetti P.J., and Corthesy B. Secretory component: a new role in secretory IgA-mediated immune exclusion in vivo. Immunity 17 (2002) 107-115
14. Fernandez M.I., Pedron T., Tournebize R., Olivo-Marin J.C., Sansonetti P.J., and Phalipon A. Anti-inflammatory role for intracellular dimeric immunoglobulin a by neutralization of lipopolysaccharide in epithelial cells. Immunity 18 (2003) 739-749
15. Yan H., Lamm M.E., Bjorling E., and Huang Y.T. Multiple functions of immunoglobulin A in mucosal defense against viruses: an in vitro measles virus model. J. Virol. 76 (2002) 10972-10979
16. Kaetzel C.S., Robinson J.K., Chintalacharuvu K.R., Vaerman J.P., and Lamm M.E. The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA. Proc. Natl. Acad. Sci. U. S. A. 88 (1991) 8796-8800
17. Williams I.R. Chemokine receptors and leukocyte trafficking in the mucosal immune system. Immunol. Res. 29 (2004) 283-292
18. Kunkel E.J., Campbell J.J., Haraldsen G., Pan J., Boisvert J., Roberts A.I., Ebert E.C., Vierra M.A., Goodman S.B., Genovese M.C., Wardlaw A.J., Greenberg H.B., Parker C.M., Butcher E.C., Andrew D.P., and Agace W.W. Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. J. Exp. Med. 192 (2000) 761-768
19. Papadakis K.A., Prehn J., Nelson V., Cheng L., Binder S.W., Ponath P.D., Andrew D.P., and Targan S.R. The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system. J. Immunol. 165 (2000) 5069-5076
20. Zabel B.A., Agace W.W., Campbell J.J., Heath H.M., Parent D., Roberts A.I., Ebert E.C., Kassam N., Qin S., Zovko M., LaRosa G.J., Yang L.L., Soler D., Butcher E.C., Ponath P.D., Parker C.M., and Andrew D.P. Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis. J. Exp. Med. 190 (1999) 1241-1256
21. Kunkel E.J., and Butcher E.C. Plasma-cell homing. Nat. Rev. Immunol. 3 (2003) 822-829
22. Stagg A.J., Kamm M.A., and Knight S.C. Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin. Eur. J. Immunol. 32 (2002) 1445-1454
23. Johansson-Lindbom B., Svensson M., Wurbel M.A., Malissen B., Marquez G., and Agace W. Selective generation of gut tropic T cells in gut-associated lymphoid tissue (GALT): requirement for GALT dendritic cells and adjuvant. J. Exp. Med. 198 (2003) 963-969
24. Mora J.R., Bono M.R., Manjunath N., Weninger W., Cavanagh L.L., Rosemblatt M., and Von Andrian U.H. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424 (2003) 88-93
25. Iwata M., Hirakiyama A., Eshima Y., Kagechika H., Kato C., and Song S.Y. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21 (2004) 527-538
26. Mowat A.M. Anatomical basis of tolerance and immunity to intestinal antigens. Nat. Rev. Immunol. 3 (2003) 331-341
27. Levine M.M. Can needle-free administration of vaccines become the norm in global immunization?. Nat. Med. 9 (2003) 99-103
28. O'Hagan D.T., and Singh M. Microparticles as vaccine adjuvants and delivery systems. Expert Rev. Vaccines 2 (2003) 269-283
29. O'Hagan D.T. Microparticles and polymers for the mucosal delivery of vaccines. Adv. Drug Deliv. Rev. 34 (1998) 305-320
30. Eldridge J.H., Meulbroek J.A., Staas J.K., Tice T.R., and Gilley R.M. Vaccine-containing biodegradable microspheres specifically enter the gut-associated lymphoid tissue following oral administration and induce a disseminated mucosal immune response. Adv. Exp. Med. Biol. 251 (1989) 191-202
31. Lutsiak M.E., Robinson D.R., Coester C., Kwon G.S., and Samuel J. Analysis of poly(d,l-lactic-co-glycolic acid) nanosphere uptake by human dendritic cells and macrophages in vitro. Pharm. Res. 19 (2002) 1480-1487
32. Newman K.D., Elamanchili P., Kwon G.S., and Samuel J. Uptake of poly(d,l-lactic-co-glycolic acid) microspheres by antigen-presenting cells in vivo. J. Biomed. Mater. Res. 60 (2002) 480-486
33. Okada H., and Toguchi H. Biodegradable microspheres in drug delivery. Crit. Rev. Ther. Drug Carr. Syst. 12 (1995) 1-99
34. Putney S.D., and Burke P.A. Improving protein therapeutics with sustained-release formulations. Nat. Biotechnol. 16 (1998) 153-157
35. Katz D.E., DeLorimier A.J., Wolf M.K., Hall E.R., Cassels F.J., van Hamont J.E., Newcomer R.L., Davachi M.A., Taylor D.N., and McQueen C.E. Oral immunization of adult volunteers with microencapsulated enterotoxigenic Escherichia coli (ETEC) CS6 antigen. Vaccine 21 (2003) 341-346
36. Singh M., Briones M., and O'Hagan D.T. A novel bioadhesive intranasal delivery system for inactivated influenza vaccines. J. Control. Release 70 (2001) 267-276
37. O'Hagan D.T., and Valiante N.M. Recent advances in the discovery and delivery of vaccine adjuvants. Nat. Rev. Drug Discov. 2 (2003) 727-735
38. Peppoloni S., Ruggiero P., Contorni M., Morandi M., Pizza M., Rappuoli R., Podda A., and Del Giudice G. Mutants of the Escherichia coli heat-labile enterotoxin as safe and strong adjuvants for intranasal delivery of vaccines. Expert Rev. Vaccines 2 (2003) 285-293
39. Gregoriadis G. Immunological adjuvants: a role for liposomes. Immunol. Today 11 (1990) 89-97
40. Harokopakis E., Hajishengallis G., and Michalek S.M. Effectiveness of liposomes possessing surface-linked recombinant B subunit of cholera toxin as an oral antigen delivery system. Infect. Immun. 66 (1998) 4299-4304
41. Childers N.K., Miller K.L., Tong G., Llarena J.C., Greenway T., Ulrich J.T., and Michalek S.M. Adjuvant activity of monophosphoryl lipid A for nasal and oral immunization with soluble or liposome-associated antigen. Infect. Immun. 68 (2000) 5509-5516
42. Moser C., Metcalfe I.C., and Viret J.F. Virosomal adjuvanted antigen delivery systems. Expert Rev. Vaccines 2 (2003) 189-196
43. Durrer P., Gluck U., Spyr C., Lang A.B., Zurbriggen R., Herzog C., and Gluck R. Mucosal antibody response induced with a nasal virosome-based influenza vaccine. Vaccine 21 (2003) 4328-4334
44. Guerrero R.A., Ball J.M., Krater S.S., Pacheco S.E., Clements J.D., and Estes M.K. Recombinant Norwalk virus-like particles administered intranasally to mice induce systemic and mucosal (fecal and vaginal) immune responses. J. Virol. 75 (2001) 9713-9722
45. Shi W., Liu J., Huang Y., and Qiao L. Papillomavirus pseudovirus: a novel vaccine to induce mucosal and systemic cytotoxic T-lymphocyte responses. J. Virol. 75 (2001) 10139-10148
46. Zhang H., Huang Y., Fayad R., Spear G.T., and Qiao L. Induction of mucosal and systemic neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) by oral immunization with bovine papillomavirus-HIV-1 gp41 chimeric virus-like particles. J. Virol. 78 (2004) 8342-8348
47. Cox J.C., Sjolander A., and Barr I.G. ISCOMs and other saponin based adjuvants. Adv. Drug Deliv. Rev. 32 (1998) 247-271
48. Ennis F.A., Cruz J., Jameson J., Klein M., Burt D., and Thipphawong J. Augmentation of human influenza A virus-specific cytotoxic T lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS). Virology 259 (1999) 256-261
49. Smith R.E., Donachie A.M., and Mowat A.M. Immune stimulating complexes as mucosal vaccines. Immunol. Cell Biol. 76 (1998) 263-269
50. Mowat A.M., Smith R.E., Donachie A.M., Furrie E., Grdic D., and Lycke N. Oral vaccination with immune stimulating complexes. Immunol. Lett. 65 (1999) 133-140
51. Hu K.F., Lovgren-Bengtsson K., and Morein B. Immunostimulating complexes (ISCOMs) for nasal vaccination. Adv. Drug Deliv. Rev. 51 (2001) 149-159
52. van der Lubben I.M., Verhoef J.C., Borchard G., and Junginger H.E. Chitosan and its derivatives in mucosal drug and vaccine delivery. Eur. J. Pharm. Sci. 14 (2001) 201-207
53. Illum L. Chitosan and its use as a pharmaceutical excipient. Pharm. Res. 15 (1998) 1326-1331
54. Dodane V., Amin Khan M., and Merwin J.R. Effect of chitosan on epithelial permeability and structure. Int. J. Pharm. 182 (1999) 21-32
55. Schipper N.G., Olsson S., Hoogstraate J.A., deBoer A.G., Varum K.M., and Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement. Pharm. Res. 14 (1997) 923-929
56. Baudner B.C., Giuliani M.M., Verhoef J.C., Rappuoli R., Junginger H.E., and Giudice G.D. The concomitant use of the LTK63 mucosal adjuvant and of chitosan-based delivery system enhances the immunogenicity and efficacy of intranasally administered vaccines. Vaccine 21 (2003) 3837-3844
57. Baudner B.C., Morandi M., Giuliani M.M., Verhoef J.C., Junginger H.E., Costantino P., Rappuoli R., and Del Giudice G. Modulation of immune response to group C meningococcal conjugate vaccine given intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl chitosan delivery system. J. Infect. Dis. 189 (2004) 828-832
58. McNeela E.A., O'Connor D., Jabbal-Gill I., Illum L., Davis S.S., Pizza M., Peppoloni S., Rappuoli R., and Mills K.H. A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery. Vaccine 19 (2000) 1188-1198
59. Otterlei M., Varum K.M., Ryan L., and Espevik T. Characterization of binding and TNF-alpha-inducing ability of chitosans on monocytes: the involvement of CD14. Vaccine 12 (1994) 825-832
60. Nishimura K., Nishimura S., Nishi N., Saiki I., Tokura S., and Azuma I. Immunological activity of chitin and its derivatives. Vaccine 2 (1984) 93-99
61. Spangler B.D. Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol. Rev. 56 (1992) 622-647
62. Mrsny R.J., Daugherty A.L., Fryling C.M., and FitzGerald D.J. Mucosal administration of a chimera composed of Pseudomonas exotoxin and the gp120 V3 loop sequence of HIV-1 induces both salivary and serum antibody responses. Vaccine 17 (1999) 1425-1433
63. Fasano A. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann. N Y Acad. Sci. 915 (2000) 214-222
64. Wu Y., Wang X., Csencsits K.L., Haddad A., Walters N., and Pascual D.W. M cell-targeted DNA vaccination. Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 9318-9323
65. Rappuoli R., Pizza M., Douce G., and Dougan G. Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. Immunol. Today 20 (1999) 493-500
66. Holmgren J., and Czerkinsky C. Cholera as a model for research on mucosal immunity and development of oral vaccines. Curr. Opin. Immunol. 4 (1992) 387-391
67. Di Tommaso A., Saletti G., Pizza M., Rappuoli R., Dougan G., Abrignani S., Douce G., and De Magistris M.T. Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant. Infect. Immun. 64 (1996) 974-979
68. Porgador A., Staats H.F., Faiola B., Gilboa E., and Palker T.J. Intranasal immunization with CTL epitope peptides from HIV-1 or ovalbumin and the mucosal adjuvant cholera toxin induces peptide-specific CTLs and protection against tumor development in vivo. J. Immunol. 158 (1997) 834-841
69. Simmons C.P., Mastroeni P., Fowler R., Ghaem-maghami M., Lycke N., Pizza M., Rappuoli R., and Dougan G. MHC class I-restricted cytotoxic lymphocyte responses induced by enterotoxin-based mucosal adjuvants. J. Immunol. 163 (1999) 6502-6510
70. Marinaro M., Riccomi A., Rappuoli R., Pizza M., Fiorelli V., Tripiciano A., Cafaro A., Ensoli B., and De Magistris M.T. Mucosal delivery of the human immunodeficiency virus-1 Tat protein in mice elicits systemic neutralizing antibodies, cytotoxic T lymphocytes and mucosal IgA. Vaccine 21 (2003) 3972-3981
71. Sun J.B., Eriksson K., Li B.L., Lindblad M., Azem J., and Holmgren J. Vaccination with dendritic cells pulsed in vitro with tumor antigen conjugated to cholera toxin efficiently induces specific tumoricidal CD8+ cytotoxic lymphocytes dependent on cyclic AMP activation of dendritic cells. Clin. Immunol. 112 (2004) 35-44
72. Yamamoto S., Takeda Y., Yamamoto M., Kurazono H., Imaoka K., Fujihashi K., Noda M., Kiyono H., and McGhee J.R. Mutants in the ADP-ribosyltransferase cleft of cholera toxin lack diarrheagenicity but retain adjuvanticity. J. Exp. Med. 185 (1997) 1203-1210
73. Cheng E., Cardenas-Freytag L., and Clements J.D. The role of cAMP in mucosal adjuvanticity of Escherichia coli heat-labile enterotoxin (LT). Vaccine 18 (1999) 38-49
74. Pizza M., Giuliani M.M., Fontana M.R., Monaci E., Douce G., Dougan G., Mills K.H., Rappuoli R., and Del Giudice G. Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants. Vaccine 19 (2001) 2534-2541
75. van Ginkel F.W., Jackson R.J., Yuki Y., and McGhee J.R. Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J. Immunol. 165 (2000) 4778-4782
76. Hagiwara Y., Iwasaki T., Asanuma H., Sato Y., Sata T., Aizawa C., Kurata T., and Tamura S. Effects of intranasal administration of cholera toxin (or Escherichia coli heat-labile enterotoxin) B subunits supplemented with a trace amount of the holotoxin on the brain. Vaccine 19 (2001) 1652-1660
77. Agren L.C., Ekman L., Lowenadler B., and Lycke N.Y. Genetically engineered nontoxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit. J. Immunol. 158 (1997) 3936-3946
78. Eriksson A.M., Schon K.M., and Lycke N.Y. The cholera toxin-derived CTA1-DD vaccine adjuvant administered intranasally does not cause inflammation or accumulate in the nervous tissues. J. Immunol. 173 (2004) 3310-3319
79. Fasano A., Baudry B., Pumplin D.W., Wasserman S.S., Tall B.D., Ketley J.M., and Kaper J.B. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions. Proc. Natl. Acad. Sci. U. S. A. 88 (1991) 5242-5246
80. Savarino S.J., Fasano A., Robertson D.C., and Levine M.M. Enteroaggregative Escherichia coli elaborate a heat-stable enterotoxin demonstrable in an in vitro rabbit intestinal model. J. Clin. Invest. 87 (1991) 1450-1455
81. Marinaro M., Di Tommaso A., Uzzau S., Fasano A., and De Magistris M.T. Zonula occludens toxin is a powerful mucosal adjuvant for intranasally delivered antigens. Infect. Immun. 67 (1999) 1287-1291
82. Marinaro M., Fasano A., and De Magistris M.T. Zonula occludens toxin acts as an adjuvant through different mucosal routes and induces protective immune responses. Infect. Immun. 71 (2003) 1897-1902
83. Vines R.R., Perdue S.S., Moncrief J.S., Sentz D.R., Barroso L.A., Wright R.L., and Wilkins T.D. Fragilysin, the enterotoxin from Bacteroides fragilis, enhances the serum antibody response to antigen co-administered by the intranasal route. Vaccine 19 (2000) 655-660
84. Castagliuolo I., Sardina M., Brun P., DeRos C., Mastrotto C., Lovato L., and Palu G. Clostridium difficile toxin A carboxyl-terminus peptide lacking ADP-ribosyltransferase activity acts as a mucosal adjuvant. Infect. Immun. 72 (2004) 2827-2836
85. Ohmura-Hoshino M., Yamamoto M., Yuki Y., Takeda Y., and Kiyono H. Non-toxic Stx derivatives from Escherichia coli possess adjuvant activity for mucosal immunity. Vaccine 22 (2004) 3751-3761
86. Ryan M., McCarthy L., Rappuoli R., Mahon B.P., and Mills K.H. Pertussis toxin potentiates Th1 and Th2 responses to co-injected antigen: adjuvant action is associated with enhanced regulatory cytokine production and expression of the co-stimulatory molecules B7-1, B7-2 and CD28. Int. Immunol. 10 (1998) 651-662
87. Munro P., Flatau G., Anjuere F., Hofman V., Czerkinsky C., and Lemichez E. The Rho GTPase activators CNF1 and DNT bacterial toxins have mucosal adjuvant properties. Vaccine 23 (2005) 2551-2556
88. Klinman D.M. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat. Rev. Immunol. 4 (2004) 249-258
89. Harandi A.M., and Holmgren J. CpG DNA as a potent inducer of mucosal immunity: implications for immunoprophylaxis and immunotherapy of mucosal infections. Curr. Opin. Investig. Drugs 5 (2004) 141-145
90. Klinman D.M. CpG DNA as a vaccine adjuvant. Expert Rev. Vaccines 2 (2003) 305-315
91. McCluskie M.J., Weeratna R.D., Payette P.J., and Davis H.L. The potential of CpG oligodeoxynucleotides as mucosal adjuvants. Crit. Rev. Immunol. 21 (2001) 103-120
92. Salkowski C.A., Detore G.R., and Vogel S.N. Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages. Infect. Immun. 65 (1997) 3239-3247
93. Moore A., McCarthy L., and Mills K.H. The adjuvant combination monophosphoryl lipid A and QS21 switches T cell responses induced with a soluble recombinant HIV protein from Th2 to Th1. Vaccine 17 (1999) 2517-2527
94. Ulrich J. MPLr-immunostimulant: adjuvant formulation. In: O'Hagan D.T., and Totowa N.J. (Eds). Vaccine Adjuvants: Preparation Methods and Research Protocols (2000), Humana Press
95. Wheeler A.W., Marshall J.S., and Ulrich J.T. A Th1-inducing adjuvant, MPL, enhances antibody profiles in experimental animals suggesting it has the potential to improve the efficacy of allergy vaccines. Int. Arch. Allergy Immunol. 126 (2001) 135-139
96. Kensil C.R., Patel U., Lennick M., and Marciani D. Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. J. Immunol. 146 (1991) 431-437
97. Kensil C., and Kammer R. QS-21: water-soluble triterpene glycoside adjuvant. Expert Opin. Investig. Drugs 7 (1998) 1475
98. Bangham A.D., Horne R.W., Glauert A.M., Dingle J.T., and Lucy J.A. Action of saponin on biological cell membranes. Nature 196 (1962) 952-955
99. Boyaka P.N., Marinaro M., Jackson R.J., van Ginkel F.W., Cormet-Boyaka E., Kirk K.L., Kensil C.R., and McGhee J.R. Oral QS-21 requires early IL-4 help for induction of mucosal and systemic immunity. J. Immunol. 166 (2001) 2283-2290
100. Villinger F. Cytokines as clinical adjuvants: how far are we?. Expert Rev. Vaccines 2 (2003) 317-326
101. Kensil C.R., Mo A.X., and Truneh A. Current vaccine adjuvants: an overview of a diverse class. Front. Biosci. 9 (2004) 2972-2988
102. Staats H.F., and Ennis Jr. F.A. IL-1 is an effective adjuvant for mucosal and systemic immune responses when coadministered with protein immunogens. J. Immunol. 162 (1999) 6141-6147
103. Boyaka P.N., Marinaro M., Jackson R.J., Menon S., Kiyono H., Jirillo E., and McGhee J.R. IL-12 is an effective adjuvant for induction of mucosal immunity. J. Immunol. 162 (1999) 122-128
104. Staats H.F., Bradney C.P., Gwinn W.M., Jackson S.S., Sempowski G.D., Liao H.X., Letvin N.L., and Haynes B.F. Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization. J. Immunol. 167 (2001) 5386-5394
105. Lee S., Gierynska M., Eo S.K., Kuklin N., and Rouse B.T. Influence of DNA encoding cytokines on systemic and mucosal immunity following genetic vaccination against herpes simplex virus. Microbes Infect. 5 (2003) 571-578
106. Bracci L., Canini I., Puzelli S., Sestili P., Venditti M., Spada M., Donatelli I., Belardelli F., and Proietti E. Type I IFN is a powerful mucosal adjuvant for a selective intranasal vaccination against influenza virus in mice and affects antigen capture at mucosal level. Vaccine 23 (2005) 2994-3004
107. Lillard Jr. J.W., Boyaka P.N., Hedrick J.A., Zlotnik A., and McGhee J.R. Lymphotactin acts as an innate mucosal adjuvant. J. Immunol. 162 (1999) 1959-1965
108. Lillard Jr. J.W., Boyaka P.N., Taub D.D., and McGhee J.R. RANTES potentiates antigen-specific mucosal immune responses. J. Immunol. 166 (2001) 162-169
109. Lillard Jr. J.W., Singh U.P., Boyaka P.N., Singh S., Taub D.D., and McGhee J.R. MIP-1alpha and MIP-1beta differentially mediate mucosal and systemic adaptive immunity. Blood 101 (2003) 807-814
110. Lillard Jr. J.W., Boyaka P.N., Chertov O., Oppenheim J.J., and McGhee J.R. Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 651-656
111. Hantman M.J., Hohmann E.L., Murphy C.G., Knipe D.M., and Miller S.I. Antigen delivery systems: development of recombinant live vaccines using viral or bacterial vectors. In: Ogra P.L., Mestecky J., Lamm M.E., Strober W., McGhee J.R., and Bienenstock J. (Eds). Mucosal Immunology (1999), Academic Press
112. Abreu M.T., Fukata M., and Arditi M. TLR signaling in the gut in health and disease. J. Immunol. 174 (2005) 4453-4460
113. Chatfield S.N., Charles I.G., Makoff A.J., Oxer M.D., Dougan G., Pickard D., Slater D., and Fairweather N.F. Use of the nirB promoter to direct the stable expression of heterologous antigens in Salmonella oral vaccine strains: development of a single-dose oral tetanus vaccine. Biotechnology (N Y) 10 (1992) 888-892
114. Lagranderie M., Murray A., Gicquel B., Leclerc C., and Gheorghiu M. Oral immunization with recombinant BCG induces cellular and humoral immune responses against the foreign antigen. Vaccine 11 (1993) 1283-1290
115. Stratford R., McKelvie N.D., Hughes N.J., Aldred E., Wiseman C., Curtis J., Bellaby T., Bentley M., Hindle Z., Brennan F.R., Chatfield S.N., Dougan G., and Khan S.A. Optimization of Salmonella enterica serovar typhi DeltaaroC DeltassaV derivatives as vehicles for delivering heterologous antigens by chromosomal integration and in vivo inducible promoters. Infect. Immun. 73 (2005) 362-368
116. Bumann D., Hueck C., Aebischer T., and Meyer T.F. Recombinant live Salmonella spp. for human vaccination against heterologous pathogens. FEMS Immunol. Med. Microbiol. 27 (2000) 357-364
117. Tacket C.O., Galen J., Sztein M.B., Losonsky G., Wyant T.L., Nataro J., Wasserman S.S., Edelman R., Chatfield S., Dougan G., and Levine M.M. Safety and immune responses to attenuated Salmonella enterica serovar typhi oral live vector vaccines expressing tetanus toxin fragment C. Clin. Immunol. 97 (2000) 146-153
118. McFadden G. Poxvirus tropism. Nat. Rev. Microbiol. 3 (2005) 201-213
119. Tatsis N., and Ertl H.C. Adenoviruses as vaccine vectors. Molec. Ther. 10 (2004) 616-629
120. Shaw D.M., Gaerthe B., Leer R.J., Van Der Stap J.G., Smittenaar C., Heijne Den Bak-Glashouwer M., Thole J.E., Tielen F.J., Pouwels P.H., and Havenith C.E. Engineering the microflora to vaccinate the mucosa: serum immunoglobulin G responses and activated draining cervical lymph nodes following mucosal application of tetanus toxin fragment C-expressing lactobacilli. Immunology 100 (2000) 510-518
121. Medaglini D., Ciabattini A., Spinosa M.R., Maggi T., Marcotte H., Oggioni M.R., and Pozzi G. Immunization with recombinant Streptococcus gordonii expressing tetanus toxin fragment C confers protection from lethal challenge in mice. Vaccine 19 (2001) 1931-1939
122. Walcher P., Mayr U.B., Azimpour-Tabrizi C., Eko F.O., Jechlinger W., Mayrhofer P., Alefantis T., Mujer C.V., DelVecchio V.G., and Lubitz W. Antigen discovery and delivery of subunit vaccines by nonliving bacterial ghost vectors. Expert Rev. Vaccines 3 (2004) 681-691
123. Douce G., Turcotte C., Cropley I., Roberts M., Pizza M., Domenghini M., Rappuoli R., and Dougan G. Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proc. Natl. Acad. Sci. U. S. A. 92 (1995) 1644-1648
124. Fraser S.A., de Haan L., Hearn A.R., Bone H.K., Salmond R.J., Rivett A.J., Williams N.A., and Hirst T.R. Mutant Escherichia coli heat-labile toxin B subunit that separates toxoid-mediated signaling and immunomodulatory action from trafficking and delivery functions. Infect. Immun. 71 (2003) 1527-1537
125. Gagliardi M.C., Sallusto F., Marinaro M., Vendetti S., Riccomi A., and De Magistris M.T. Effects of the adjuvant cholera toxin on dendritic cells: stimulatory and inhibitory signals that result in the amplification of immune responses. Int. J. Med. Microbiol. 291 (2002) 571-575
126. Gagliardi M.C., Sallusto F., Marinaro M., Langenkamp A., Lanzavecchia A., and De Magistris M.T. Cholera toxin induces maturation of human dendritic cells and licences them for Th2 priming. Eur. J. Immunol. 30 (2000) 2394-2403
127. Gagliardi M.C., and De Magistris M.T. Maturation of human dendritic cells induced by the adjuvant cholera toxin: role of cAMP on chemokine receptor expression. Vaccine 21 (2003) 856-861
128. Braun M.C., He J., Wu C.Y., and Kelsall B.L. Cholera toxin suppresses interleukin (IL)-12 production and IL-12 receptor beta1 and beta2 chain expression. J. Exp. Med. 189 (1999) 541-552
129. Eriksson K., Fredriksson M., Nordstrom I., and Holmgren J. Cholera toxin and its B subunit promote dendritic cell vaccination with different influences on Th1 and Th2 development. Infect. Immun. 71 (2003) 1740-1747
130. Shreedhar V.K., Kelsall B.L., and Neutra M.R. Cholera toxin induces migration of dendritic cells from the subepithelial dome region to T- and B-cell areas of Peyer's patches. Infect. Immun. 71 (2003) 504-509
131. Anjuere F., Luci C., Lebens M., Rousseau D., Hervouet C., Milon G., Holmgren J., Ardavin C., and Czerkinsky C. In vivo adjuvant-induced mobilization and maturation of gut dendritic cells after oral administration of cholera toxin. J. Immunol. 173 (2004) 5103-5111
132. Glenn G.M., Rao M., Matyas G.R., and Alving C.R. Skin immunization made possible by cholera toxin. Nature 391 (1998) 851
133. Glenn G.M., Taylor D.N., Li X., Frankel S., Montemarano A., and Alving C.R. Transcutaneous immunization: a human vaccine delivery strategy using a patch. Nat. Med. 6 (2000) 1403-1406
134. Mawas F., Peyre M., Beignon A.S., Frost L., Del Giudice G., Rappuoli R., Muller S., Sesardic D., and Partidos C.D. Successful induction of protective antibody responses against Haemophilus influenzae type b and diphtheria after transcutaneous immunization with the glycoconjugate polyribosyl ribitol phosphate-cross-reacting material 197 vaccine. J. Infect. Dis. 190 (2004) 1177-1182
135. Thanavala Y., Mahoney M., Pal S., Scott A., Richter L., Natarajan N., Goodwin P., Arntzen C.J., and Mason H.S. Immunogenicity in humans of an edible vaccine for hepatitis B. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 3378-3382
136. Tacket C.O. Plant-derived vaccines against diarrheal diseases. Vaccine 23 (2005) 1866-1869
137. Hale C., Humphreys I.R., Hussell T., Bowe F., Clare S., Pickard D., Preston A., Del Giudice G., and Dougan G. Mucosal immunisation of murine neonates using whole cell and acellular pertussis vaccines. Vaccine 22 (2004) 3595-3602
138. Capozzo A.V., Cuberos L., Levine M.M., and Pasetti M.F. Mucosally delivered Salmonella live vector vaccines elicit potent immune responses against a foreign antigen in neonatal mice born to naive and immune mothers. Infect. Immun. 72 (2004) 4637-4646
139. Ugozzoli M., Mariani M., Del Giudice G., Soenawan E., and O'Hagan D.T. Combinations of protein polysaccharide conjugate vaccines for intranasal immunization. J. Infect. Dis. 186 (2002) 1358-1361
140. King Jr. J.C., Lagos R., Bernstein D.I., Piedra P.A., Kotloff K., Bryant M., Cho I., and Belshe R.B. Safety and immunogenicity of low and high doses of trivalent live cold-adapted influenza vaccine administered intranasally as drops or spray to healthy children. J. Infect. Dis. 177 (1998) 1394-1397
141. Piedra P.A., Yan L., Kotloff K., Zangwill K., Bernstein D.I., King J., Treanor J., Munoz F., Wolff M., Cho I., Mendelman P.M., Cordova J., and Belshe R.B. Safety of the trivalent, cold-adapted influenza vaccine in preschool-aged children. Pediatrics 110 (2002) 662-672
142. Belshe R., Lee M.S., Walker R.E., Stoddard J., and Mendelman P.M. Safety, immunogenicity and efficacy of intranasal, live attenuated influenza vaccine. Expert Rev. Vaccines 3 (2004) 643-654
143. Sansonetti P.J. War and peace at mucosal surfaces. Nat. Rev. Immunol. 4 (2004) 953-964
144. Iwasaki A., and Kelsall B.L. Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (MIP)-3alpha, MIP-3beta, and secondary lymphoid organ chemokine. J. Exp. Med. 191 (2000) 1381-1394
145. Smythies L.E., Sellers M., Clements R.H., Mosteller-Barnum M., Meng G., Benjamin W.H., Orenstein J.M., and Smith P.D. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J. Clin. Invest. 115 (2005) 66-75
146. Siegrist C.A. Neonatal and early life vaccinology. Vaccine 19 (2001) 3331-3346
147. Del Giudice G. Vaccination strategies. An overview. Vaccine 21 Suppl. 2 (2003) S83-S88