REVIEW

Innate endogenous adjuvants prime to desirable immune responses via mucosal routes

  • Xiaoguang Wang , 1,2 ,
  • Delong Meng 3
Expand
  • 1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  • 2. School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
  • 3. School of Biology and Environmental Science, University College Dublin, Dublin, Ireland

Received date: 29 Oct 2014

Accepted date: 18 Nov 2014

Published date: 01 Apr 2015

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Vaccination is an effective strategy to prevent infectious or immune related diseases, which has made remarkable contribution in human history. Recently increasing attentions have been paid to mucosal vaccination due to its multiple advantages over conventional ways. Subunit or peptide antigens are more reasonable immunogens for mucosal vaccination than live or attenuated pathogens, however adjuvants are required to augment the immune responses. Many mucosal adjuvants have been developed to prime desirable immune responses to different etiologies. Compared with pathogen derived adjuvants, innate endogenous molecules incorporated into mucosal vaccines demonstrate prominent adjuvanticity and safety. Nowadays, cytokines are broadly used as mucosal adjuvants for participation of signal transduction of immune responses, activation of innate immunity and polarization of adaptive immunity. Desired immune responses are promptly and efficaciously primed on basis of specific interactions between cytokines and corresponding receptors. In addition, some other innate molecules are also identified as potent mucosal adjuvants. This review focuses on innate endogenous mucosal adjuvants, hoping to shed light on the development of mucosal vaccines.

Cite this article

Xiaoguang Wang , Delong Meng . Innate endogenous adjuvants prime to desirable immune responses via mucosal routes[J]. Protein & Cell, 2015 , 6(3) : 170 -184 . DOI: 10.1007/s13238-014-0125-1

1
Abraham E, Shah S (1992) Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-speciflc pulmonary secretory antibody-response. J Immunol149: 3719-3726

2
Arulanandam BP, Metzger DW (1999) Modulation of mucosal and systemic immunity by intranasal interleukin 12 delivery. Vaccine17: 252-260

DOI

3
Arulanandam BP, O’Toole M, Metzger DW (1999) Intranasal interleukin-12 is a powerful adjuvant for protective mucosal immunity. J Infect Dis180: 940-949

DOI

4
Arulanandam BP, Lynch JM, Briles DE, Hollingshead S, Metzger DW (2001) Intranasal vaccination with pneumococcal surface protein A and interleukin-12 augments antibody-mediated opsonization and protective immunity against Streptococcus pneumoniae infection. Infect Immun69: 6718-6724

DOI

5
Baca-Estrada ME, Foldvari M, Snider M (1999) Induction of mucosal immune responses by administration of liposomeantigen formulations and interleukin-12. J Interferon Cytokine Res19: 455-462

DOI

6
Baggiolini M, Dahinden CA (1994) CC chemokines in allergic inflammation. Immunol Today15: 127-133

DOI

7
Baqar S, Pacheco ND, Rollwagen FM (1993) Modulation of mucosal immunity against Campylobacter jejuni by orally-administered cytokines. Antimicrob Agents Chemother37: 2688-2692

DOI

8
Baron SD, Singh R, Metzger DW (2007) Inactivated Francisella tularensis live vaccine strain protects against respiratory tularemia by intranasal vaccination in an immunoglobulin A-dependent fashion. Infect Immun75: 2152-2162

DOI

9
Batten M, Groom J, Cachero TG, Qian F, Schneider P, Tschopp J, Browning JL, Mackay F (2000) BAFF mediates survival of peripheral immature B lymphocytes. J Exp Med192: 1453-1465

DOI

10
Beilharz MW, Cummins MJ, Bennett AL, Cummins JM (2010) Oromucosal administration of interferon to humans. Pharmaceuticals3: 323-344

DOI

11
Bermudez-Humaran LG, Cortes-Perez NG, Lefevre F, Guimaraes V, Rabot S, Alcocer-Gonzalez JM, Gratadoux JJ, Rodriguez-Padilla C, Tamez-Guerra RS, Corthier G (2005) A novel mucosal vaccine based on live lactococci expressing E7 antigen and IL-12 induces systemic and mucosal immune responses and protects mice against human papillomavirus type 16-induced tumors. J Immunol175: 7297-7302

DOI

12
Bertley FMN, Kozlowski PA, Wang SW, Chappelle J, Patel J, Sonuyi O, Mazzara G, Monteflori D, Carville A, Mansfleld KG (2004) Control of simian/human immunodeflciency virus viremia and disease progression after IL-2-augmented DNA-modifled vaccinia virus Ankara nasal vaccination in nonhuman primates. J Immunol172: 3745-3757

DOI

13
Boyaka PN, Marinaro M, Jackson RJ, Menon S, Kiyono H, Jirillo E, McGhee JR (1999) IL-12 is an effective adjuvant for induction of mucosal immunity. J Immunol162: 122-128

14
Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, Van Deventer SJH, Neirynck S, Peppelenbosch MP, Steidler L (2006) A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn’s disease. Clin Gastroenterol Hepatol4: 754-759

DOI

15
Bracci L, Canini I, Puzelli S, Sestili P, Venditti M, Spada M, Donatelli I, Belardelli F, Proietti E (2005) 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. Vaccine23: 2994-3004

DOI

16
Bracci L, Canini I, Venditti M, Spada M, Puzelli S, Donatelli I, Belardelli F, Proietti E (2006) Type I IFN as a vaccine adjuvant for both systemic and mucosal vaccination against influenza virus. Vaccine24: S56-S57

DOI

17
Bracci L, La Sorsa V, Belardelli F, Proietti E (2008) Type I interferons as vaccine adjuvants against infectious diseases and cancer. Expert Rev Vaccines7: 373-381

DOI

18
Braciak TA, Gallichan WS, Graham FL, Richards CD, Ramsay AJ, Rosenthal KL, Gauldie J (2000) Recombinant adenovirus vectors expressing interleukin-5 and-6 speciflcally enhance mucosal immunoglobulin A responses in the lung. Immunology101: 388-396

DOI

19
Bradney CP, Sempowski GD, Liao HX, Haynes BF, Staats HF (2002) Cytokines as adjuvants for the induction of anti-human immunodeflciency virus peptide immunoglobulin G (IgG) and IgA antibodies in serum and mucosal secretions after nasal immunization. J Virol76: 517-524

DOI

20
Brogden KA, Heidari M, Sacco RE, Palmquist D, Guthmiller JM, Johnson GK, Jia HP, Tack BF, McCray PB (2003) Defensininduced adaptive immunity in mice and its potential in preventing periodontal disease. Oral Microbiol Immunol18: 95-99

DOI

21
Bukreyev A, Belyakov IM, Berzofsky JA, Murphy BR, Collins PL (2001) Granulocyte-macrophage colony-stimulating factor expressed by recombinant respiratory syncytial virus attenuates viral replication and increases the level of pulmonary antigenpresenting cells. J Virol75: 12128-12140

DOI

22
Cao M, Sasaki O, Yamada A, Imanishi J (1992) Enhancement of the protective effect of inactivated influenza virus vaccine by cytokines. Vaccine10: 238-242

DOI

23
Chodaczek G, Zimecki M, Lukasiewicz J, Lugowski C (2006) A complex of lactoferrin with monophosphoryl lipid A is an efflcient adjuvant of the humoral and cellular immune response in mice. Med Microbiol Immunol195: 207-216

DOI

24
Chun S, Daheshia M, Lee S, Eo SK, Rouse BT (1999) Distribution fate and mechanism of immune modulation following mucosal delivery of plasmid DNA encoding IL-10. J Immunol163: 2393-2402

25
Couch RB, Atmar RL, Cate TR, Quarles JM, Keitel WA, Arden NH, Wells J, Nino D, Wyde PR (2009) Contrasting effects of type I interferon as a mucosal adjuvant for influenza vaccine in mice and humans. Vaccine27: 5344-5348

DOI

26
Cox E, Verdonck F, Vanrompay D, Goddeeris B (2006) Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa. Vet Res37: 511-539

DOI

27
De Magistnis MT (2006) Mucosal delivery of vaccine antigens and its advantages in pediatrics. Adv Drug Deliv Rev58: 52-67

DOI

28
Degre M, Bukholm G (1995) Orally administered interferon-gamma but not tumor necrosis factor-alpha suppress infection with Salmonella typhimurium in a mouse model. J Biol Regul Homeost Agents9: 15-20

29
Dinarello CA (2000) Proinflammatory cytokines. Chest118: 503-508

DOI

30
Drexler HG, Quentmeier H (2004) FLT3: receptor and ligand. Growth Factors22: 71-73

DOI

31
Egan MA, Chong SY, Hagen M, Megati S, Schadeck EB, Piacente P, Ma BJ, Monteflori DC, Haynes BF, Israel ZR (2004) A comparative evaluation of nasal and parenteral vaccine adjuvants to elicit systemic and mucosal HIV-1 peptide-speciflc humoral immune responses in cynomolgus macaques. Vaccine22: 3774-3788

DOI

32
Eo SK, Lee S, Chun S, Rouse BT (2001a) Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines. J Virol75: 569-578

DOI

33
Eo SK, Lee S, Kumaraguru U, Rouse BT (2001b) Immunopotentiation of DNA vaccine against herpes simplex virus via co-delivery of plasmid DNA expressing CCR7 ligands. Vaccine19: 4685-4693

DOI

34
Ferko B, Kittel C, Romanova J, Sereinig S, Katinger H, Egorov A (2006) Live attenuated influenza virus expressing human interleukin-2 reveals increased immunogenic potential in young and aged hosts. J Virol80: 11621-11627

DOI

35
Fukuiwa T, Sekine S, Kobayashi R, Suzuki H, Kataoka K, Gilbert RS, Kurono Y, Boyaka PN, Krieg AM, McGhee JR (2008) A combination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity. Vaccine26: 4849-4859

DOI

36
Giudice EL, Campbell JD (2006) Needle-free vaccine delivery. Adv Drug Deliv Rev58: 68-89

DOI

37
Griffln KF, Eyles JE, Spiers ID, Alpar HO, Williamson ED (2002) Protection against plague following immunisation with microencapsulated V antigen is reduced by co-encapsulation with IFNgamma or IL-4, but not IL-6. Vaccine20: 3650-3657

DOI

38
Gwinn WM, Kirwan SM, Wang SH, Ashcraft KA, Sparks NL, Doil CR, Tlusty TG, Casey LS, Hollingshead SK, Briles DE (2010) Effective induction of protective systemic immunity with nasally administered vaccines adjuvantedwith IL-1. Vaccine28: 6901-6914

DOI

39
Hanazawa T, Antuni JD, Kharitonov SA, Barnes PJ (2000) Intranasal administration of eotaxin increases nasal eosinophils and nitric oxide in patients with allergic rhinitis. J Allergy Clin Immunol105: 58-64

DOI

40
Hinc K, Stasilojc M, Piatek I, Peszynska-Sularz G, Isticato R, Ricca E, Obuchowski M, Iwanicki A (2014) Mucosal adjuvant activity of IL-2 presenting spores of Bacillus subtilis in a murine model of Helicobacter pylori vaccination. Plos One9: e95187

DOI

41
Holmgren J, Czerkinsky C (2005) Mucosal immunity and vaccines. Nat Med11: S45-S53

DOI

42
Holmgren J, Czerkinsky C, Eriksson K, Mharandi A (2003) Mucosal immunisation and adjuvants: a brief overview of recent advances and challenges. Vaccine21: S89-S95

DOI

43
Hu K, Luo S, Tong L, Huang X, Jin W, Huang W, Du T, Yan Y, He S, Griffln GE (2013) CCL19 and CCL28 augment mucosal and systemic immune responses to HIV-1 gp140 by mobilizing responsive immunocytes into secondary lymph nodes and mucosal tissue. J Immunol191: 1935-1947

DOI

44
Huber VC, Arulanandam BP, Arnaboldi PM, Elmore MK, Sheehan CE, Kallakury BV, Metzger DW (2003) Delivery of IL-12 intranasally leads to reduced IL-12-mediated toxicity. Int Immunopharmacol3: 801-809

DOI

45
Inoue T, Inoue Y, Nakamura T, Yoshida A, Inoue Y, Tano Y, Shimomura Y, Fujisawa Y, Aono A, Hayashi K (2002) The effect of immunization with herpes simplex virus glycoprotein D fused with interleukin-2 against murine herpetic keratitis. Jpn J Ophthalmol46: 370-376

DOI

46
Jang YS, Kim SH, Lee HY, Lee H, Kim J, Kim DH, Lee KY (2013) The cathelicidin LL-37 exerts its mucosal adjuvant activity via enhancing germinal center formation and dendritic cell maturation. J Immunol190: 124

47
Kalled SL (2006) Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody production. Semin Immunol18: 290-296

DOI

48
Kataoka K, McGhee JR, Kobayashi R, Fujihashi K, Shizukuishi S, Fujihashi K (2004) Nasal Flt3 ligand cDNA elicits CD11c(+)CD8 (+) dendritic cells for enhanced mucosal immunity. J Immunol172: 3612-3619

DOI

49
Kataoka K, Fujihashi K, Oma K, Fukuyama Y, Hollingshead SK, Sekine S, Kawabata S, Ito HO, Briles DE, Oishi K (2011) The nasal dendritic cell-targeting Flt3 ligand as a safe adjuvant elicits effective protection against fatal pneumococcal pneumonia. Infect Immun79: 2819-2828

DOI

50
Kaul D, Ogra PL (1998) Mucosal responses to parenteral and mucosal vaccines. Dev Biol Stand95: 141-146

51
Kayamuro H, Abe Y, Yoshioka Y, Katayama K, Nomura T, Yoshida T, Yamashita K, Yoshikawa T, Kawai Y, Mayumi T (2009a) The use of a mutant TNF-alpha as a vaccine adjuvant for the induction of mucosal immune responses. Biomaterials30: 5869-5876

DOI

52
Kayamuro H, Yoshioka Y, Abe Y, Katayama K, Yoshida T, Yamashita K, Yoshikawa T, Hiroi T, Itoh N, Kawai Y (2009b) TNF superfamily member, TL1A, is a potential mucosal vaccine adjuvant. Biochem Biophys Res Commun384: 296-300

DOI

53
Kayamuro H, Abe Y, Yoshioka Y, Katayama K, Yoshida T, Yamashita K, Yoshikawa T, Kawai Y, Mayumi T, Hiroi T (2010a) Mutant TNF-alpha, mTNF-K90R, is a novel candidate adjuvant for a mucosal vaccine against HIV. Pharmazie65: 254-256

54
Kayamuro H, Yoshioka Y, Abe Y, Arita S, Katayama K, Nomura T, Yoshikawa T, Kubota-Koketsu R, Ikuta K, Okamoto S (2010b) Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus. J Virol84: 12703-12712

DOI

55
Kayamuro H, Yoshioka Y, Abe Y, Katayama K, Arita S, Nomura T, Yoshikawa T, Itoh N, Kamada H, Tsunoda S (2011) Identiflcation of new candidates as mucosal vaccine adjuvant in TNF family cytokines. In: Advances in TNF family research, Springer New York, pp 299-304

DOI

56
Kim HD, Cao YP, Kong FK, Van Kampen KR, Lewis TL, Ma ZD, Tang DCC, Fukuchi KI (2005) Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid beta-protein and GM-CSF. Vaccine23: 2977-2986

DOI

57
Kodama S, Hirano T, Noda K, Abe N, Suzuki M (2010) A single nasal dose of fms-like tyrosine kinase receptor-3 ligand, but not peritoneal application, enhances nontypeable Haemophilus influenzae-speciflc long-term mucosal immune responses in the nasopharynx. Vaccine28: 2510-2516

DOI

58
Kodama S, Abe N, Hirano T, Suzuki M (2011) A single nasal dose of CCL20 chemokine induces dendritic cell recruitment and enhances nontypable Haemophilus influenzae-speciflc immune responses in the nasal mucosa. Acta Otolaryngol131: 989-996

DOI

59
Kokuryo S, Inoue H, Fukuizumi T, Tsujisawa T, Tominaga K, Fukuda J (2002) Evaluation of interleukin 1 as a mucosal adjuvant in immunization with Streptococcus sobrinus cells by tonsillar application in rabbits. Oral Microbiol Immunol 17: 163-171

DOI

60
Kruzel ML, Zimecki M (2002) Lactoferrin and immunologic dissonance: Clinical implications. Arch Immunol Ther Exp50: 399-410

61
Lee S, Gierynska M, Eo SK, Kuklin N, Rouse BT (2003) Influence of DNA encoding cytokines on systemic and mucosal immunity following genetic vaccination against herpes simplex virus. Microbes Infect5: 571-578

DOI

62
Levine MM (2003) Can needle-free administration of vaccines become the norm in global immunization? Nat Med9: 99-103

DOI

63
Lillard JW, Boyaka PN, Chertov O, Oppenheim JJ, McGhee JR (1999a) Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc Natl Acad Sci USA96: 651-656

DOI

64
Lillard JW, Boyaka PN, Hedrick JA, Zlotnik A, McGhee JR (1999b) Lymphotactin acts as an innate mucosal adjuvant. J Immunol162: 1959-1965

65
Lillard JW, Boyaka PN, Taub DD, McGhee JR (2001) RANTES potentiates antigen-speciflc mucosal immune responses. J Immunol166: 162-169

DOI

66
Lillard JW Jr, Singh UP, Boyaka PN, Singh S, Taub DD, McGhee JR (2003) MIP-1alpha and MIP-1beta differentially mediate mucosal and systemic adaptive immunity. Blood101: 807-814

DOI

67
Lu Y, Xin KQ, Hamajima K, Tsuji T, Aoki I, Yang J, Sasaki S, Fukushima J, Yoshimura T, Toda S (1999) Macrophage inflammatory protein-1 alpha (MIP-1 alpha) expression plasmid enhances DNA vaccine-induced immune response against HIV-1. Clin Exp Immunol115: 335-341

DOI

68
Lynch JM, Briles DE, Metzger DW (2003) Increased protection against pneumococcal disease by mucosal administration of conjugate vaccine plus interleukin-12. Infect Immun71: 4780-4788

DOI

69
Manrique M, Kozlowski PA, Cobo-Molinos A, Wang SW, Wilson RL, Monteflori DC, Mansfleld KG, Carville A, Aldovini A(2011) Long-term control of simian immunodeflciency virus (mac251) viremia to undetectable levels in half of infected female rhesus macaques nasally vaccinated with simian immunodeflciency virus DNA/ recombinant modifled vaccinia virus ankara. J Immunol186: 3581-3593

DOI

70
Marinaro M, Boyaka PN, Jackson RJ, Finkelman FD, Kiyono H, Jirillo E, McGhee JR (1999) Use of intranasal IL-12 to target predominantly Th1 responses to nasal and Th2 responses to oral vaccines given with cholera toxin. J Immunol162: 114-121

71
McBride S, Hoebe K, Georgel P, Janssen E (2006) Cell-associated double-stranded RNA enhances antitumor activity through the production of type IIFN. J Immunol177: 6122-6128

DOI

72
Mcghee JR, Mestecky J, Dertzbaugh MT, Eldridge JH, Hirasawa M, Kiyono H (1992) The mucosal immune system from fundamental concepts to vaccine development. Vaccine10: 75-88

DOI

73
McNeela EA, Mills KHG (2001) Manipulating the immune system: humoral versus cell-mediated immunity. Adv Drug Deliver Rev51: 43-54

DOI

74
Meritet JF, Maury C, Tovey MG (2001) Effect of oromucosal administration of IFN-alpha on allergic sensitization and the hypersensitive inflammatory response in animals sensitized to ragweed pollen. J Interferon Cytokine Res21: 583-593

DOI

75
Mutsch M, Zhou WG, Rhodes P, Bopp M, Chen RT, Linder T, Spyr C, Steffen R (2004) Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. New Engl J Med350: 896-903

DOI

76
Namangala B, Inoue N, Kohara J, Kuboki N, Sakurai T, Hayashida K, Sugimoto C (2006) Evidence for the immunostimulatory effects of low-dose orally delivered human IFN-alpha in cattle. J Interferon Cytokine Res26: 675-681

DOI

77
Nambiar JK, Ryan AA, Kong CU, Britton WJ, Triccas JA (2010) Modulation of pulmonary DC function by vaccine-encoded GMCSF enhances protective immunity against Mycobacterium tuberculosis infection. Eur J Immunol40: 153-161

DOI

78
Niethammer AG, Xiang R, Ruehlmann JM, Lode HN, Dolman CS, Gillies SD, Reisfeld RA (2001) Targeted interleukin 2 therapy enhances protective immunity induced by an autologous oral DNA vaccine against murine melanoma. Cancer Res 61: 6178-6184

79
Oh YK, Park JS, Yoon H, Kim CK (2003) Enhanced mucosal and systemic immune responses to a vaginal vaccine coadministered with RANTES-expressing plasmid DNA using in situ-gelling mucoadhesive delivery system. Vaccine21: 1980-1988

DOI

80
O’Hagan DT, Rappuoli R (2004) Novel approaches to vaccine delivery. Pharm Res21: 1519-1530

DOI

81
Okada E, Sasaki S, Ishii N, Aoki I, Yasuda T, Nishioka K, Fukushima J, Miyazaki J, Wahren B, Okuda K (1997) Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens. J Immunol159: 3638-3647

82
Pabst R, Luhrmann A, Steinmetz I, Tschernig T (2003) A single intratracheal dose of the growth factor Fms-like tyrosine kinase receptor-3 ligand induces a rapid differential increase of dendritic cells and lymphocyte subsets in lung tissue and bronchoalveolar lavage, resulting in an increased local antibody production. J Immunol171: 325-330

DOI

83
Parker JN, Pflster LA, Quenelle D, Gillespie GY, Markert JM, Kern ER, Whitley RJ (2006) Genetically engineered herpes simplex viruses that express IL-12 or GM-CSF as vaccine candidates. Vaccine24: 1644-1652

DOI

84
Pockley AG, Montgomery PC (1991) In vivo adjuvant effect of interleukins 5 and 6 on rat tear IgA antibody responses. Immunology73: 19-23

85
Proietti E, Bracci L, Puzelli S, Di Pucchio T, Sestili P, De Vincenzi E, Venditti M, Capone I, Seif I, De Maeyer E (2002) Type I IFN as a natural adjuvant for a protective immune response: lessons from the influenza vaccine model. J Immunol169: 375-383

DOI

86
Ramsay AJ, Kohonencorish M (1993) Interleukin-5 expressed by a recombinant virus vector enhances speciflc mucosal IgA responses in vivo. Eur J Immunol23: 3141-3145

DOI

87
Ramsburg E, Publicover J, Buonocore L, Poholek A, Robek M, Palin A, Rose JK (2005) A vesicular stomatitis virus recombinant expressing granulocyte-macrophage colony-stimulating factor induces enhanced T-cell responses and is highly attenuated for replication in animals. J Virol79: 15043-15053

DOI

88
Sabirov A, Metzger DW (2006) Intranasal vaccination of neonatal mice with polysaccharide conjugate vaccine for protection against pneumococcal otitis media. Vaccine24: 5584-5592

DOI

89
Scheerlinck JPY (2001) Genetic adjuvants for DNA vaccines. Vaccine19: 2647-2656

DOI

90
Sekine S, Kataoka K, Fukuyama Y, Adachi Y, Davydova J, Yamamoto M, Kohayashi R, Fujihashi K, Suzuki H, Curiel DT (2008) A novel adenovirus expressing Flt3 ligand enhances mucosal immunity by inducing mature nasopharyngeal-associated lymphoreticular tissue dendritic cell migration. J Immunol180: 8126-8134

DOI

91
Shanmugham LN, Petrarca C, Frydas S, Donelan J, Castellani ML, Boucher W, Madhappan B, Tete S, Falasca K, Conti P (2006) IL-15 an immunoregulatory and anti-cancer cytokine. Recent advances. J Exp Clin Cancer Res25: 529-536

92
Staats HF, Ennis FA (1999) IL-1 is an effective adjuvant for mucosal and systemic immune responses when coadministered with protein immunogens. J Immunol162: 6141-6147

93
Staats HF, Bradney CP, Gwinn WM, Jackson SS, Sempowski GD, Liao HX, Letvin NL, Haynes BF (2001) Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization. J Immunol167: 5386-5394

DOI

94
Steidler L, Robinson K, Chamberlain L, Schofleld KM, Remaut E, Le Page RW, Wells JM (1998) Mucosal delivery of murine interleukin-2 (IL-2) and IL-6 by recombinant strains of Lactococcus lactis coexpressing antigen and cytokine. Infect Immun66: 3183-3189

95
Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E (2000) Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science289: 1352-1355

DOI

96
Sui Y, Gagnon S, Dzutsev A, Zhu Q, Yu H, Hogg A, Wang Y, Xia Z, Belyakov IM, Venzon D (2011) TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4(+) memory T cell loss in SIVmac251-challenged rhesus macaques. Vaccine30: 59-68

DOI

97
Sun K, Salmon SL, Lotz SA, Metzger DW (2007) Interleukin-12 promotes gamma interferon-dependent neutrophil recruitment in the lung and improves protection against respiratory Streptococcus pneumoniae infection. Infect Immun75: 1196-1202

DOI

98
Tertilt C, Joh J, Krause A, Chou PG, Schneeweiss K, Crystal RG, Worgall S (2009) Expression of B-cell activating factor enhances protective immunity of a vaccine against Pseudomonas aeruginosa. Infect Immun77: 3044-3055

DOI

99
Thompson AL, Staats HF (2011) Cytokines: the future of intranasal vaccine adjuvants. Clin Dev Immunol2011: 289597

DOI

100
Thompson AL, Johnson BT, Sempowski GD, Gunn MD, Hou B, DeFranco AL, Staats HF (2012) Maximal adjuvant activity of nasally delivered IL-1 alpha requires adjuvant-responsive CD11c (+) cells and does not correlate with adjuvant-induced in vivo cytokine production. J Immunol188: 2834-2846

DOI

101
Toka FN, Rouse BT (2005) Mucosal application of plasmid-encoded IL-15 sustains a highly protective anti-Herpes simplex virus immunity. J Leukoc Biol78: 178-186

DOI

102
Toka FN, Gierynska M, Rouse BT (2003) Codelivery of CCR7 ligands as molecular adjuvants enhances the protective immune response against herpes simplex virus type 1. J Virol77: 12742-12752

DOI

103
Toka FN, Pack CD, Rouse BT (2004) Molecular adjuvants for mucosal immunity. Immunol Rev199: 100-112

DOI

104
Tovey MG (2002) Oromucosal cytokine therapy: mechanism(s) of action. Taehan Kan Hakhoe Chi8: 125-131

105
Tovey MG, Maury C (1999) Oromucosal interferon therapy: marked antiviral and antitumor activity. J Interferon Cytokine Res19: 145-155

DOI

106
Tovey MG, Lallemand C, Thyphronitis G (2008) Adjuvant activity of type I interferons. Biol Chem389: 541-545

DOI

107
Trinchieri G (1995) Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-speciflc adaptive immunity. Annu Rev Immunol13: 251-276

DOI

108
Van Roey GA, Arias MA, Tregoning JS, Rowe G, Shattock RJ (2012) Thymic stromal lymphopoietin (TSLP) acts as a potent mucosal adjuvant for HIV-1 gp140 vaccination in mice. Eur J Immunol42: 353-363

DOI

109
Vansnick J (1990) Interleukin-6: an overview. Annu Rev Immunol8: 253-278

DOI

110
Walker DM (2004) Oral mucosal immunology: an overview. Ann Acad Med Singap33: 27-30

111
Wang X, Zhang XY, Kang YM, Jin HL, Du XG, Zhao G, Yu Y, Li JY, Su BW, Huang C (2008) Interleukin-15 enhance DNA vaccine elicited mucosal and systemic immunity against foot and mouth disease virus. Vaccine26: 5135-5144

DOI

112
Watanabe Y, Matsumoto Y, Kikuchi R, Kiriyama M, Nakagawa K, Nomura H, Maruyama K, Matsumoto M (1995) Pharmacokinetics and pharmacodynamics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following intranasal administration in rabbits. J Drug Targ3: 231-238

DOI

113
Watford WT, Moriguchi M, Morinobu A, O’Shea JJ (2003) The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev14: 361-368

DOI

114
Weaver CT, Hatton RD, Mangan PR, Harrington LE (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol25: 821-852

DOI

115
Wierzbicki A, Kiszka I, Kaneko H, Kmieciak D, Wasik TJ, Gzyl J, Kaneko Y, Kozbor D (2002) Immunization strategies to augment oral vaccination with DNA and viral vectors expressing HIV envelope glycoprotein. Vaccine20: 1295-1307

DOI

116
Wijesundara DK, Xi Y, Ranasinghe C (2014) Unraveling the convoluted biological roles of type I interferons in infection and immunity: a way forward for therapeutics and vaccine design. Front Immunol5: 412

DOI

117
Williamson E, Westrich GT, Viney JL (1999) Modulating dendritic cells to optimize mucosal immunization protocols. J Immunol163: 3668-3675

118
Wright AKA, Christopoulou I, El Batrawy S, Limer J, Gordon SB (2011) rhIL-12 as adjuvant augments lung cell cytokine responses to pneumococcal whole cell antigen. Immunobiology216: 1143-1147

DOI

119
Xin KQ, Hamajima K, Sasaki S, Honsho A, Tsuji T, Ishii N, Cao XR, Lu Y, Fukushima J, Shapshak P (1998) Intranasal administration of human immunodeflciency virus type-1 (HIV-1) DNA vaccine with interleukin-2 expression plasmid enhances cellmediated immunity against HIV-1. Immunology94: 438-444

DOI

120
Xin KQ, Hamajima K, Sasaki S, Tsuji T, Watabe S, Okada E, Okuda K (1999a) IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA vaccine. Vaccine17: 858-866

DOI

121
Xin KQ, Lu Y, Hamajima K, Fukushima J, Yang J, Inamura K, Okuda K (1999b) Immunization of RANTES expression plasmid with a DNA vaccine enhances HIV-1-speciflc immunity. Clin Immunol92: 90-96

DOI

122
Xu LY, Yang JS, Huang YM, Levi M, Link H, Xiao BG (2000) Combined nasal administration of encephalitogenic myelin basic protein peptide 68-86 and IL-10 suppressed incipient experimental allergic encephalomyelitis in Lewis rats. Clin Immunol96: 205-211

DOI

123
Zhang X, Yu Q, Zhang X, Yang Q (2009) Co-administration of inactivated avian influenza virus with CpG or rIL-2 strongly enhances the local immune response after intranasal immunization in chicken. Vaccine27: 5628-5632

DOI

124
Zhang HX, Qiu YY, Zhao YH, Liu XT, Liu M, Yu AL (2014) Immunogenicity of oral vaccination with Lactococcus lactis derived vaccine candidate antigen (UreB) of Helicobacter pylon fused with the human interleukin 2 as adjuvant. Mol Cell Probes28: 25-30

DOI

125
Zhou M, Zhang G, Ren G, Gnanadurai CW, Li Z, Chai Q, Yang Y, Leyson CM, Wu W, Cui M (2013) Recombinant rabies viruses expressing GM-CSF or flagellin are effective vaccines for both intramuscular and oral immunizations. PLoS One8: e63384

DOI

Outlines

/