Mucosal vaccines: Novel advances in technology and delivery

Expert Review of Vaccines

Volumn 8, Issue 8, 2009, Pages 1083-1097

  Yuki, Yoshikazu ^a   Kiyono, Hiroshi ^a  

^a UNIVERSITY OF TOKYO   (Japan)

Author keywords

MucoRice ; Nasal vaccine; Oral vaccine; Transcutaneous vaccine

Indexed keywords

CAIV T; CHOLERA GARDE; CHOLERA VACCINE; HOLAVAX TYPHOID; INFLUENZA VACCINE; MUCORICE; MUCOSAL VACCINE; ORAL POLIOMYELITIS VACCINE; ROTAVIRUS VACCINE; TYPHOID VACCINE; UNCLASSIFIED DRUG; VACCINE;

CHOLERA; CLINICAL TRIAL; DRUG DELIVERY SYSTEM; DRUG TARGETING; HUMAN; IMMUNE SYSTEM; IMMUNITY; INFLUENZA; INFLUENZA VIRUS; MEDICAL TECHNOLOGY; NONHUMAN; POLIOMYELITIS; PRIORITY JOURNAL; RESPIRATORY TRACT INFECTION; REVIEW; RICE; ROOM TEMPERATURE; ROTAVIRUS; TRAVELLER DIARRHEA; TUBERCULOSIS; TYPHOID FEVER; VIRUS INFECTION;

ADMINISTRATION, CUTANEOUS; ADMINISTRATION, INTRANASAL; ADMINISTRATION, ORAL; ADMINISTRATION, SUBLINGUAL; BACTERIAL VACCINES; BIOMEDICAL RESEARCH; HUMANS; VIRAL VACCINES;

EID: 68049124726     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/erv.09.61     Document Type: Review

References (115)

1. Yuki Y, Nochi T, Kiyono H. Progress towards an AIDS mucosal vaccine: an overview. Tuberculosis (Edinb.) 87(Suppl. 1), S35-S44 (2007).
2. Holmgren J, Czerkinsky C. Mucosal immunity and vaccines. Nat. Med. 11(4 Suppl.), S45-S53 (2005). • Excellent review of mucosal vaccine and mucosal immunity.
3. Quiding M, Nordstrom I, Kilander A et al. Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-g production and evokes local immunological memory. J. Clin. Invest. 88(1), 143-148 (1991).
4. Johansson EL, Wassen L, Holmgren J, Jertborn M, Rudin A. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans. Infect. Immun. 69(12), 7481-7486 (2001).
5. Czerkinsky C, Anjuere F, McGhee JR et al. Mucosal immunity and tolerance: relevance to vaccine development. Immunol. Rev. 170, 197-222 (1999).
6. Mestecky J, Russell MW, Elson CO. Perspectives on mucosal vaccines: is mucosal tolerance a barrier? J. Immunol. 179(9), 5633-5638 (2007).
7. Yuki Y, Kiyono H. New generation of mucosal adjuvants for the induction of protective immunity. Rev. Med. Virol. 13(5), 293-310 (2003).
8. Kunisawa J, Kiyono H. A marvel of mucosal T cells and secretory antibodies for the creation of first lines of defense. Cell Mol. Life Sci. 62(12), 1308-1321 (2005).
9. Kiyono H, Fukuyama S. NALT- versus Peyer's-patch-mediated mucosal immunity. Nat. Rev. Immunol. 4(9), 699-710 (2004).
10. Neutra MR, Kozlowski PA. Mucosal vaccines: the promise and the challenge. Nat. Rev. Immunol. 6(2), 148-158 (2006).
11. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. Class switch recombination and hypermutation require activationinduced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102(5), 553-563 (2000).
12. Stagg AJ, Kamm MA, Knight SC. Intestinal dendritic cells increase T cell expression of a4b7 integrin. Eur. J. Immunol. 32(5), 1445-1454 (2002).
13. Johansson-Lindbom B, Svensson M, Wurbel MA, Malissen B, Marquez G, 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(6), 963-969 (2003).
14. Mora JR, Bono MR, Manjunath N et al. Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells. Nature 424(6944), 88-93 (2003).
15. Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21(4), 527-538 (2004).
16. Mora JR, Iwata M, Eksteen B et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 314(5802), 1157-1160 (2006).
17. Campbell JJ, Brightling CE, Symon FA et al. Expression of chemokine receptors by lung T cells from normal and asthmatic subjects. J. Immunol. 166(4), 2842-2848 (2001).
18. Kunisawa J, Fukuyama S, Kiyono H. Mucosa-associated lymphoid tissues in the aerodigestive tract: their shared and divergent traits and their importance to the orchestration of the mucosal immune system. Curr. Mol. Med. 5(6), 557-572 (2005).
19. McGhee JR, Fujihashi K, Beagley KW, Kiyono H. Role of interleukin-6 in human and mouse mucosal IgA plasma cell responses. Immunol. Res. 10(3-4), 418-422 (1991).
20. Kaetzel CS. The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunol. Rev. 206, 83-99 (2005).
21. Brandtzaeg P, Prydz H. Direct evidence for an integrated function of J chain and secretory component in epithelial transport of immunoglobulins. Nature 311(5981), 71-73 (1984).
22. Neutra MR, Frey A, Kraehenbuhl JP. Epithelial M cells: gateways for mucosal infection and immunization. Cell 86(3), 345-348 (1996).
23. Iwasaki A. Mucosal dendritic cells. Annu. Rev. Immunol. 25, 381-418 (2007).
24. Rescigno M, Urbano M, Valzasina B et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2(4), 361-367 (2001).
25. Jang MH, Kweon MN, Iwatani K et al. Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc. Natl Acad. Sci. USA 101(16), 6110-6115 (2004).
26. Romani N, Ratzinger G, Pfaller K et al. Migration of dendritic cells into lymphatics - the Langerhans cell example: routes, regulation, and relevance. Int. Rev. Cytol. 207, 237-270 (2001).
27. Glenn GM, Rao M, Matyas GR, Alving CR. Skin immunization made possible by cholera toxin. Nature 391(6670), 851 (1998).
28. Cuburu N, Kweon MN, Song JH et al. Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine 25(51), 8598-8610 (2007).
29. Girard MP, Steele D, Chaignat CL, Kieny MP. A review of vaccine research and development: human enteric infections. Vaccine 24(15), 2732-2750 (2006).
30. Chumakov K, Ehrenfeld E, Wimmer E, Agol VI. Vaccination against polio should not be stopped. Nat. Rev. Microbiol. 5(12), 952-958 (2007).
31. He Y, Mueller S, Chipman PR et al. Complexes of poliovirus serotypes with their common cellular receptor, CD155. J. Virol. 77(8), 4827-4835 (2003).
32. Prevots DR, Sutter RW, Strebel PM, Weibel RE, Cochi SL. Completeness of reporting for paralytic poliomyelitis, United States, 1980 through 1991. Implications for estimating the risk of vaccine-associated disease. Arch. Pediatr. Adolesc. Med. 148(5), 479-485 (1994).
33. Kew O, Morris-Glasgow V, Landaverde M et al. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science 296(5566), 356-359 (2002). • Report regarding vaccinederived poliomyelitis.
34. Sack DA, Sack RB, Nair GB, Siddique AK. Cholera. Lancet 363(9404), 223-233 (2004).
35. Levine MM, Kaper JB. Live oral vaccines against cholera: an update. Vaccine 11(2), 207-212 (1993).
36. Su-Arehawaratana P, Singharaj P, Taylor DN et al. Safety and immunogenicity of different immunization regimens of CVD 103-HgR live oral cholera vaccine in soldiers and civilians in Thailand. J. Infect. Dis. 165(6), 1042-1048 (1992).
37. Richie EE, Punjabi NH, Sidharta YY et al. Efficacy trial of single-dose live oral cholera vaccine CVD 103-HgR in North Jakarta, Indonesia, a cholera-endemic area. Vaccine 18(22), 2399-2410 (2000).
38. Clemens JD, Sack DA, Harris JR et al. Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. Lancet 335(8684), 270-273 (1990).
39. Clemens JD, Sack DA, Harris JR et al. Impact of B subunit killed whole-cell and killed whole-cell-only oral vaccines against cholera upon treated diarrhoeal illness and mortality in an area endemic for cholera. Lancet 1(8599), 1375-1379 (1988).
40. Clemens JD, Sack DA, Harris JR et al. Field trial of oral cholera vaccines in Bangladesh. Lancet 2(8499), 124-127 (1986).
41. Ali M, Emch M, von Seidlein L et al. Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis. Lancet 366(9479), 44-49 (2005).
42. Lucas ME, Deen JL, von Seidlein L et al. Effectiveness of mass oral cholera vaccination in Beira, Mozambique. N. Engl. J. Med. 352(8), 757-767 (2005).
43. Clemens JD, Sack DA, Harris JR et al. Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial. J. Infect. Dis. 158(2), 372-377 (1988).
44. Kenner JR, Coster TS, Taylor DN et al. Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae O1. J. Infect. Dis. 172(4), 1126-1129 (1995).
45. Qadri F, Chowdhury MI, Faruque SM et al. Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh. J. Infect. Dis. 192(4), 573-579 (2005).
46. Qadri F, Chowdhury MI, Faruque SM et al. Peru-15, a live attenuated oral cholera Vaccine is safe and immunogenic in Bangladeshi toddlers and infants. Vaccine 25(2), 231-238 (2007).
47. Garmory HS, Brown KA, Titball RW. Salmonella vaccines for use in humans: present and future perspectives. FEMS Microbiol. Rev. 26(4), 339-353 (2002).
48. Sinha A, Sazawal S, Kumar R et al. Typhoid fever in children aged less than 5 years. Lancet 354(9180), 734-737 (1999).
49. Klugman KP, Koornhof HJ, Robbins JB, Le Cam NN. Immunogenicity, efficacy and serological correlate of protection of Salmonella typhi Vi capsular polysaccharide vaccine three years after immunization. Vaccine 14(5), 435-438 (1996).
50. Kossaczka Z, Lin FY, Ho VA et al. Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam. Infect. Immun. 67(11), 5806-5810 (1999).
51. Gentschev I, Spreng S, Sieber H et al. Vivotif - a 'magic shield' for protection against typhoid fever and delivery of heterologous antigens. Chemotherapy, 53(3), 177-180 (2007).
52. Levine MM, Ferreccio C, Abrego P, Martin OS, Ortiz E, Cryz S. Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine 17 Suppl 2, S22-27 (1999).
53. Dietrich G, Griot-Wenk M, Metcalfe IC, Lang AB, Viret JF. Experience with registered mucosal vaccines. Vaccine 21(7-8), 678-683 (2003).
54. Salerno-Goncalves R, Pasetti MF, Sztein MB. Characterization of CD8+ effector T cell responses in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J. Immunol. 169(4), 2196-2203 (2002).
55. Nakagomi O, Cunliffe NA. Rotavirus vaccines: entering a new stage of deployment. Curr. Opin. Infect. Dis. 20(5), 501-507 (2007).
56. DiPetrillo MD, Tibbetts T, Kleanthous H, Killeen KP, Hohmann EL. Safety and immunogenicity of phoP/phoQ-deleted Salmonella typhi expressing Helicobacter pylori urease in adult volunteers. Vaccine 18(5-6), 449-459 (1999).
57. Witherell GW. Oral typhoid vaccine. Acambis/Berna. Curr. Opin. Investig. Drugs 4(8), 1010-1018 (2003).
58. Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerg. Infect. Dis. 9(5), 565-572 (2003).
59. Santos N, Hoshino Y. Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev. Med. Virol. 15(1), 29-56 (2005).
60. Bines J. Intussusception and rotavirus vaccines. Vaccine 24(18), 3772-3776 (2006).
61. Simonsen L, Morens D, Elixhauser A, Gerber M, Van Raden M, Blackwelder W. Effect of rotavirus vaccination programme on trends in admission of infants to hospital for intussusception. Lancet 358(9289), 1224-1229 (2001).
62. Bernstein DI, Sack DA, Rothstein E et al. Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial. Lancet 354(9175), 287-290 (1999).
63. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N. Engl. J. Med. 354(1), 11-22 (2006).
64. Vesikari T, Matson DO, Dennehy P et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N. Engl. J. Med. 354(1), 23-33 (2006).
65. Franco MA, Angel J, Greenberg HB. Immunity and correlates of protection for rotavirus vaccines. Vaccine 24(15), 2718-2731 (2006).
66. Michaud CM, Murray CJ, Bloom BR. Burden of disease - implications for future research. JAMA 285(5), 535-539 (2001).
67. Girard MP, Cherian T, Pervikov Y, Kieny MP. A review of vaccine research and development: human acute respiratory infections. Vaccine 23(50), 5708-5724 (2005).
68. Izurieta HS, Thompson WW, Kramarz P et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N. Engl. J. Med. 342(4), 232-239 (2000).
69. Cox RJ, Brokstad KA, Ogra P. Influenza virus: immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines. Scand. J. Immunol. 59(1), 1-15 (2004).
70. Belshe RB. Current status of live attenuated influenza virus vaccine in the US. Virus Res. 103(1-2), 177-185 (2004).
71. Youngner JS, Treanor JJ, Betts RF, Whitaker-Dowling P. Effect of simultaneous administration of coldadapted and wild-type influenza A viruses on experimental wild-type influenza infection in humans. J. Clin. Microbiol. 32(3), 750-754 (1994).
72. Maassab HF. Adaptation and growth characteristics of influenza virus at 25 degrees C. Nature 213(5076), 612-614 (1967). •• Original paper of cold-adapted influenza virus that is used as the first nasal influenza vaccine.
73. Belshe RB, Edwards KM, Vesikari T et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N. Engl. J. Med. 356(7), 685-696 (2007).
74. Durbin AP, Karron RA. Progress in the development of respiratory syncytial virus and parainfluenza virus vaccines. Clin. Infect. Dis. 37(12), 1668-1677 (2003).
75. Tang RS, MacPhail M, Schickli JH et al. Parainfluenza virus type 3 expressing the native or soluble fusion (F) protein of respiratory syncytial virus (RSV) confers protection from RSV infection in African green monkeys. J. Virol. 78(20), 11198-11207 (2004).
76. Flynn JL, Chan J. Immunology of tuberculosis. Annu. Rev. Immunol. 19, 93-129 (2001).
77. Skeiky YA, Sadoff JC. Advances in tuberculosis vaccine strategies. Nat. Rev. Microbiol. 4(6), 469-476 (2006).
78. Baumann U. Mucosal vaccination against bacterial respiratory infections. Expert Rev. Vaccines 7(8), 1257-1276 (2008).
79. McShane H, Pathan AA, Sander CR, Goonetilleke NP, Fletcher HA, Hill AV. Boosting BCG with MVA85A: the first candidate subunit vaccine for tuberculosis in clinical trials. Tuberculosis (Edinb.) 85(1-2), 47-52 (2005).
80. Santosuosso M, McCormick S, Zhang X, Zganiacz A, Xing Z. Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis. Infect. Immun. 74(8), 4634-4643 (2006).
81. Brandt L, Oettinger T, Holm A, Andersen AB, Andersen P. Key epitopes on the ESAT-6 antigen recognized in mice during the recall of protective immunity to Mycobacterium tuberculosis. J. Immunol. 157(8), 3527-3533 (1996).
82. Lycke N. From toxin to adjuvant: the rational design of a vaccine adjuvant vector, CTA1-DD/ISCOM. Cell Microbiol. 6(1), 23-32 (2004).
83. Mowat AM, Donachie AM, Jagewall S et al. CTA1-DD-immune stimulating complexes: a novel, rationally designed combined mucosal vaccine adjuvant effective with nanogram doses of antigen. J. Immunol. 167(6), 3398-3405 (2001).
84. Andersen CS, Dietrich J, Agger EM, Lycke NY, Lovgren K, Andersen P. The combined CTA1-DD/ISCOMs vector is an effective intranasal adjuvant for boosting prior Mycobacterium bovis BCG immunity to Mycobacterium tuberculosis. Infect. Immun. 75(1), 408-416 (2007).
85. Eriksson AM, Schon KM, Lycke NY. The cholera toxin-derived CTA1-DD vaccine adjuvant administered intranasally does not cause inflammation or accumulate in the nervous tissues. J. Immunol. 173(5), 3310-3319 (2004).
86. Goonetilleke NP, McShane H, Hannan CM, Anderson RJ, Brookes RH, Hill AV. Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guerin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J. Immunol. 171(3), 1602-1609 (2003).
87. McShane H, Pathan AA, Sander CR et al. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat. Med. 10(11), 1240-1244 (2004).
88. Giudice EL, Campbell JD. Needle-free vaccine delivery. Adv. Drug Deliv. Rev. 58(1), 68-89 (2006).
89. Glenn GM, Taylor DN, Li X, Frankel S, Montemarano A, Alving CR. Transcutaneous immunization: a human vaccine delivery strategy using a patch. Nat. Med. 6(12), 1403-1406 (2000).
90. Belyakov IM, Hammond SA, Ahlers JD, Glenn GM, Berzofsky JA. Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells. J. Clin. Invest. 113(7), 998-1007 (2004).
91. Chang SY, Cha HR, Igarashi O et al. Cutting edge: Langerin + dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk. J. Immunol. 180(7), 4361-4365 (2008).
92. Glenn GM, Villar CP, Flyer DC et al. Safety and immunogenicity of an enterotoxigenic Escherichia coli vaccine patch containing heat-labile toxin: use of skin pretreatment to disrupt the stratum corneum. Infect. Immun. 75(5), 2163-2170 (2007).
93. Steinsland H, Valentiner-Branth P, Gjessing HK, Aaby P, Molbak K, Sommerfelt H. Protection from natural infections with enterotoxigenic Escherichia coli: longitudinal study. Lancet 362(9380), 286-291 (2003).
94. Streatfield SJ, Howard JA. Plant-based vaccines. Int. J. Parasitol. 33(5-6), 479-493 (2003).
95. Ma JK, Drake PM, Christou P. The production of recombinant pharmaceutical proteins in plants. Nat. Rev. Genet. 4(10), 794-805 (2003).
96. Streatfield SJ. Mucosal immunization using recombinant plant-based oral vaccines. Methods 38(2), 150-157 (2006).
97. Haq TA, Mason HS, Clements JD, Arntzen CJ. Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 268(5211), 714-716 (1995).
98. Tacket CO, Mason HS, Losonsky G, Estes MK, Levine MM, Arntzen CJ. Human immune responses to a novel norwalk virus vaccine delivered in transgenic potatoes. J. Infect. Dis. 182(1), 302-305 (2000).
99. Tacket CO, Pasetti MF, Edelman R, Howard JA, Streatfield S. Immunogenicity of recombinant LT-B delivered orally to humans in transgenic corn. Vaccine 22(31-32), 4385-4389 (2004).
100. Nochi T, Takagi H, Yuki Y et al. Ricebased mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination. Proc. Natl Acad. Sci. USA 104(26), 10986-10991 (2007). •• First cold chain- and needle-free vaccine using rice-based delivery system.
101. Brayden DJ, Jepson MA, Baird AW. Keynote review: intestinal Peyer's patch M cells and oral vaccine targeting. Drug Discov. Today 10(17), 1145-1157 (2005).
102. Sharma R, Schumacher U, Adam E. Lectin histochemistry reveals the appearance of M-cells in Peyer's patches of SCID mice after syngeneic normal bone marrow transplantation. J. Histochem. Cytochem. 46(2), 143-148 (1998).
103. Helander A, Silvey KJ, Mantis NJ et al. The viral sigma1 protein and glycoconjugates containing a2-3-linked sialic acid are involved in type 1 reovirus adherence to M cell apical surfaces. J. Virol. 77(14), 7964-7977 (2003).
104. Manocha M, Pal PC, Chitralekha KT et al. Enhanced mucosal and systemic immune response with intranasal immunization of mice with HIV peptides entrapped in PLG microparticles in combination with Ulex Europaeus-I lectin as M cell target. Vaccine 23(48-49), 5599-5617 (2005).
105. Wu Y, Wang X, Csencsits KL, Haddad A, Walters N, Pascual DW. M cell-targeted DNA vaccination. Proc. Natl Acad. Sci. USA 98(16), 9318-9323 (2001).
106. Nochi T, Yuki Y, Matsumura A et al. A novel M cell-specific carbohydratetargeted mucosal vaccine effectively induces antigen-specific immune responses. J. Exp. Med. 204(12), 2789-2796 (2007). • M-cell-targeted vaccine using the first M cell-specific monoclonal antibody.
107. Agostinis F, Tellarini L, Canonica GW, Falagiani P, Passalacqua G. Safety of sublingual immunotherapy with a monomeric allergoid in very young children. Allergy, 60(1), 133 (2005).
108. Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and metaanalysis. Allergy, 60(1), 4-12 (2005).
109. Kweon MN, Yamamoto M, Watanabe F et al. A nontoxic chimeric enterotoxin adjuvant induces protective immunity in both mucosal and systemic compartments with reduced IgE antibodies. J. Infect. Dis. 186(9), 1261-1269 (2002).
110. Song JH, Nguyen HH, Cuburu N et al. Sublingual vaccination with influenza virus protects mice against lethal viral infection. Proc. Natl Acad. Sci. USA 105(5), 1644-1649 (2008). • One of the few experimental studies on sublingual vaccination.
111. Mutsch M, Zhou W, Rhodes P et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. N. Engl. J. Med. 350(9), 896-903 (2004).
112. van Ginkel FW, Jackson RJ, Yuki Y, McGhee JR. Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J. Immunol. 165(9), 4778-4782 (2000).
113. Kaisho T, Akira S. Toll-like receptors as adjuvant receptors. Biochim. Biophys. Acta 1589(1), 1-13 (2002).
114. Varmus H, Klausner R, Zerhouni E, Acharya T, Daar AS, Singer PA. Public health. Grand Challenges in Global Health. Science 302(5644), 398-399 (2003).
115. Curtiss RI, Cardineau CA. Oral immunisation by transgenic plants. US patent 5686079 (1998).