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Intralymphatic Vaccination

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Gene Vaccines

Abstract

The immune response is initiated by dendritic cells and other antigen-presenting cells. These cells are present in nearly all organs and tissues of the body, so that theoretically any organ or tissue could serve as a route for vaccine administration. The choice of route is therefore mainly based on practical aspects. Using conventional needle and syringe the subcutaneous or intramuscular route are standard. The dermis and especially the epidermis are technically more difficult to target, but are likely to gain more interest due to the recent development of micro-needle patches and needle free injection devices. Vaccine administration via mucosal surfaces such as nasal or oral vaccination represents another option for needle free vaccine administration.

While all the above mentioned routes of administration have been proven to work and protect against childhood diseases, influenza and many other infectious agents, the discussion and comparison of these different routes usually focuses on patient convenience, reduction of pain and distress for children, cost and on the possibility for mass vaccination. In this review, however, we would like to focus on how the route of administration can enhance the efficacy of vaccination, in clinical indications that are benefiting to a much lesser extent from conventional vaccination.

Especially in therapeutic vaccination, i.e., in a smaller patient number that already suffers from a disease, vaccination efficiency rather than convenience is the main issue. This is particularly the case in therapeutic cancer vaccines and in allergen specific immunotherapy. Intralymphatic vaccination is a strategy to maximize immunogenicity and therefore vaccine efficacy. The main part of this review will discuss this long known vaccination route and its clinical applicability in therapeutic vaccination, with a special focus on gene vaccines.

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References

  • Adamina M, Rosenthal R, Weber WP, Frey DM, Viehl CT, Bolli M, Huegli RW, Jacob AL, Heberer M, Oertli D, Marti W, Spagnoli GC, Zajac P (2010) Intranodal immunization with a vaccinia virus encoding multiple antigenic epitopes and costimulatory molecules in metastatic melanoma. Mol Ther 18(3):651–659

    Article  PubMed  CAS  Google Scholar 

  • Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC (2005) Prevalences of positive skin test responses to 10 common allergens in the US population: results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol 116(2):377–383

    Article  PubMed  Google Scholar 

  • Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811

    Article  PubMed  CAS  Google Scholar 

  • Barratt-Boyes SM, Watkins SC, Finn OJ (1997) Migration of cultured chimpanzee dendritic cells following intravenous and subcutaneous injection. Adv Exp Med Biol 417:71–75

    PubMed  CAS  Google Scholar 

  • Barratt-Boyes SM, Zimmer MI, Harshyne LA, Meyer EM, Watkins SC, Capuano S III, Murphey-Corb M, Falo LD Jr, Donnenberg AD (2000) Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J Immunol 164(5):2487–2495

    PubMed  CAS  Google Scholar 

  • Bogers WM, Bergmeier LA, Ma J, Oostermeijer H, Wang Y, Kelly CG, Ten Haaft P, Singh M, Heeney JL, Lehner T (2004a) A novel HIV-CCR5 receptor vaccine strategy in the control of mucosal SIV/HIV infection. AIDS 18(1):25–36

    Article  PubMed  Google Scholar 

  • Bogers WM, Bergmeier LA, Oostermeijer H, ten Haaft P, Wang Y, Kelly CG, Singh M, Heeney JL, Lehner T (2004b) CCR5 targeted SIV vaccination strategy preventing or inhibiting SIV infection. Vaccine 22(23–24):2974–2984

    Article  PubMed  CAS  Google Scholar 

  • Bot A, Stan AC, Inaba K, Steinman R, Bona C (2000) Dendritic cells at a DNA vaccination site express the encoded influenza nucleoprotein and prime MHC class I-restricted cytolytic lymphocytes upon adoptive transfer. Int Immunol 12(6):825–832

    Article  PubMed  CAS  Google Scholar 

  • Bourquin C, Anz D, Zwiorek K, Lanz AL, Fuchs S, Weigel S, Wurzenberger C, von der Borch P, Golic M, Moder S, Winter G, Coester C, Endres S (2008) Targeting CpG oligonucleotides to the lymph node by nanoparticles elicits efficient antitumoral immunity. J Immunol 181(5):2990–2998

    PubMed  CAS  Google Scholar 

  • Bousquet J, Lockey R, Malling HJ (1998) Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 102(4 Pt 1):558–562

    Article  PubMed  CAS  Google Scholar 

  • Boyer P, Juillard G, Yamashiro C, McCarthy T (1976) Characterization of immune responses to tumor cells following intralymphatic immunization. Proc Am Assoc Cancer Res 17:69

    Google Scholar 

  • Brown K, Gao W, Alber S, Trichel A, Murphey-Corb M, Watkins SC, Gambotto A, Barratt-Boyes SM (2003) Adenovirus-transduced dendritic cells injected into skin or lymph node prime potent simian immunodeficiency virus-specific T cell immunity in monkeys. J Immunol 171(12):6875–6882

    PubMed  CAS  Google Scholar 

  • Carralot JP, Probst J, Hoerr I, Scheel B, Teufel R, Jung G, Rammensee HG, Pascolo S (2004) Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines. Cell Mol Life Sci 61(18):2418–2424

    Article  PubMed  CAS  Google Scholar 

  • Crameri R, Fluckiger S, Daigle I, Kundig T, Rhyner C (2007) Design, engineering and in vitro evaluation of MHC class-II targeting allergy vaccines. Allergy 62(2):197–206

    Article  PubMed  CAS  Google Scholar 

  • De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, Strijk SP, Ruers TJ, Boerman OC, Oyen WJ, Adema GJ, Punt CJ, Figdor CG (2003) Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res 63(1):12–17

    PubMed  Google Scholar 

  • de Vries IJ, Lesterhuis WJ, Barentsz JO, Verdijk P, van Krieken JH, Boerman OC, Oyen WJ, Bonenkamp JJ, Boezeman JB, Adema GJ, Bulte JW, Scheenen TW, Punt CJ, Heerschap A, Figdor CG (2005) Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23(11):1407–1413

    Article  PubMed  Google Scholar 

  • Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Noble W, Till SJ, Hamid QA, Nouri-Aria KT (1999) Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 341(7):468–475

    Article  PubMed  CAS  Google Scholar 

  • Finerty S, Stokes CR, Gruffydd-Jones TJ, Hillman TJ, Barr FJ, Harbour DA (2001) Targeted lymph node immunization can protect cats from a mucosal challenge with feline immunodeficiency virus. Vaccine 20(1–2):49–58

    Article  PubMed  CAS  Google Scholar 

  • Fong L, Brockstedt D, Benike C, Wu L, Engleman EG (2001) Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 166(6):4254–4259

    PubMed  CAS  Google Scholar 

  • Frey JR, Wenk P (1957) Experimental studies on the pathogenesis of contact eczema in the guinea-pig. Int Arch Allergy Appl Immunol 11(1–2):81–100

    Article  PubMed  CAS  Google Scholar 

  • Golden DB, Kwiterovich KA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM (1996) Discontinuing venom immunotherapy: outcome after five years. J Allergy Clin Immunol 97(2):579–587

    Article  PubMed  CAS  Google Scholar 

  • Greter M, Hofmann J, Becher B (2009) Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. PLoS Biol 7(5):e1000109

    Article  PubMed  Google Scholar 

  • Grover A, Kim GJ, Lizee G, Tschoi M, Wang G, Wunderlich JR, Rosenberg SA, Hwang ST, Hwu P (2006) Intralymphatic dendritic cell vaccination induces tumor antigen-specific, skin-homing T lymphocytes. Clin Cancer Res 12(19):5801–5808

    Article  PubMed  CAS  Google Scholar 

  • Guidry AJ, O’Brian CN, Oliver SP, Dowlen HH, Douglass LW (1994) Effect of whole Staphylococcus aureus and mode of immunization on bovine opsonizing antibodies to capsule. J Dairy Sci 77:2965–2974

    Article  PubMed  CAS  Google Scholar 

  • Heinzerling L, Basch V, Maloy K, Johansen P, Senti G, Wuthrich B, Storni T, Kundig TM (2006) Critical role for DNA vaccination frequency in induction of antigen-specific cytotoxic responses. Vaccine 24(9):1389–1394

    Article  PubMed  CAS  Google Scholar 

  • Imvision Therapeutics (2009) Positive phase I clinical results for treatment of cat dander allergy. http://www.imvision-therapeutics.com

  • Johansen P, Haffner AC, Koch F, Zepter K, Erdmann I, Maloy K, Simard JJ, Storni T, Senti G, Bot A, Wuthrich B, Kundig TM (2005) Direct intralymphatic injection of peptide vaccines enhances immunogenicity. Eur J Immunol 35(2):568–574

    Article  PubMed  CAS  Google Scholar 

  • Juillard GJ, Boyer PJ (1977) Intralymphatic immunization: current status. Eur J Cancer 13(4–5):439–440

    PubMed  CAS  Google Scholar 

  • Juillard GJ, Boyer PJ, Snow HD (1976) Intralymphatic infusion of autochthonous tumor cells in canine lymphoma. Int J Radiat Oncol Biol Phys 1(5–6):497–503

    Article  PubMed  CAS  Google Scholar 

  • Juillard GJ, Boyer PJ, Yamashiro CH, Snow HD, Weisenburger TH, McCarthy T, Miller RJ (1977) Regional intralymphatic infusion (ILI) of irradiated tumor cells with evidence of distant effects. Cancer 39(1):126–130

    Article  PubMed  CAS  Google Scholar 

  • Juillard GJ, Boyer PJ, Yamashiro CH (1978) A phase I study of active specific intralymphatic immunotherapy (ASILI). Cancer 41(6):2215–2225

    Article  PubMed  CAS  Google Scholar 

  • Juillard GJ, Boyer PJ, Niewisch H, Hom M (1979) Distribution and consequences of cell suspensions following intralymphatic infusion. Bull Cancer 66(3):217–228

    PubMed  CAS  Google Scholar 

  • Karrer U, Althage A, Odermatt B, Roberts CW, Korsmeyer SJ, Miyawaki S, Hengartner H, Zinkernagel RM (1997) On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(−)/–) mutant mice. J Exp Med 185(12):2157–2170

    Article  PubMed  CAS  Google Scholar 

  • Kawabata S, Miller CJ, Lehner T, Fujihashi K, Kubota M, McGhee JR, Imaoka K, Hioi T, Kiyono H (1998) Induction of Th2 cytokine expression for p27-specific IgA B-cell responses after targeted lymph node immunization with simian immunodeficiency virus in rhesus macaques. J Infect Dis 177:26–33

    Article  PubMed  CAS  Google Scholar 

  • Klavinskis LS, Bergmeier LA, Gao L, Mitchell E, Ward RG, Layton G, Brookes R, Meyers NJ, Lehner T (1996) Mucosal or targeted lymph node immunization of macaques with a particulate SIVp27 protein elicits virus-specific CTL in the genito-rectal mucosa and draining lymph nodes. J Immunol 157(6):2521–2527

    PubMed  CAS  Google Scholar 

  • Koopman G, Bogers WM, van Gils M, Koornstra W, Barnett S, Morein B, Lehner T, Heeney JL (2007) Comparison of intranasal with targeted lymph node immunization using PR8-Flu ISCOM adjuvanted HIV antigens in macaques. J Med Virol 79(5):474–482

    Article  PubMed  CAS  Google Scholar 

  • Kreiter S, Selmi A, Diken M, Koslowski M, Britten CM, Huber C, Tureci O, Sahin U (2010) Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity. Cancer Res 70(22):9031–9040

    Article  PubMed  CAS  Google Scholar 

  • Kundig TM, Bachmann MF, DiPaolo C, Simard JJ, Battegay M, Lother H, Gessner A, Kuhlcke K, Ohashi PS, Hengartner H et al (1995) Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science 268(5215):1343–1347

    Article  PubMed  CAS  Google Scholar 

  • Landolt GA, Hussey SB, Kreutzer K, Quintana A, Lunn DP (2010) Low-dose DNA vaccination into the submandibular lymph nodes in ponies. Vet Rec 167(8):302–303

    Article  PubMed  CAS  Google Scholar 

  • Lehner T, Bergmeier LA, Tao L, Panagiotidi C, Klavinskis LS, Hussain L, Ward RG, Meyers N, Adams SE, Gearing AJ et al (1994) Targeted lymph node immunization with simian immunodeficiency virus p27 antigen to elicit genital, rectal, and urinary immune responses in nonhuman primates. J Immunol 153(4):1858–1868

    PubMed  CAS  Google Scholar 

  • Lehner T, Wang Y, Cranage M, Bergmeier LA, Mitchell E, Tao L, Hall G, Dennis M, Cook N, Brookes R, Klavinskis L, Jones I, Doyle C, Ward R (1996) Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques. Nat Med 2(7):767–775

    Article  PubMed  CAS  Google Scholar 

  • Lehner T, Mitchell E, Bergmeier L, Singh M, Spallek R, Cranage M, Hall G, Dennis M, Villinger F, Wang Y (2000) The role of gammadelta T cells in generating antiviral factors and ­beta-chemokines in protection against mucosal simian immunodeficiency virus infection. Eur J Immunol 30(8):2245–2256

    Article  PubMed  CAS  Google Scholar 

  • Lesimple T, Moisan A, Carsin A, Ollivier I, Mousseau M, Meunier B, Leberre C, Collet B, Quillien V, Drenou B, Lefeuvre-Plesse C, Chevrant-Breton J, Toujas L (2003) Injection by various routes of melanoma antigen-associated macrophages: biodistribution and clinical effects. Cancer Immunol Immunother 52(7):438–444

    Article  PubMed  CAS  Google Scholar 

  • Lesimple T, Neidhard EM, Vignard V, Lefeuvre C, Adamski H, Labarriere N, Carsin A, Monnier D, Collet B, Clapisson G, Birebent B, Philip I, Toujas L, Chokri M, Quillien V (2006) Immunologic and clinical effects of injecting mature peptide-loaded dendritic cells by intralymphatic and intranodal routes in metastatic melanoma patients. Clin Cancer Res 12(24):7380–7388

    Article  PubMed  CAS  Google Scholar 

  • Lockey RF (2001) “ARIA”: global guidelines and new forms of allergen immunotherapy. J Allergy Clin Immunol 108(4):497–499

    Article  PubMed  CAS  Google Scholar 

  • Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC (1987) Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol 79(4):660–677

    Article  PubMed  CAS  Google Scholar 

  • Lockey RF, Turkeltaub PC, Olive ES, Hubbard JM, Baird-Warren IA, Bukantz SC (1990) The hymenoptera venom study. III: safety of venom immunotherapy. J Allergy Clin Immunol 86(5):775–780

    Article  PubMed  CAS  Google Scholar 

  • Mackensen A, Krause T, Blum U, Uhrmeister P, Mertelsmann R, Lindemann A (1999) Homing of intravenously and intralymphatically injected human dendritic cells generated in vitro from CD34+ hematopoietic progenitor cells. Cancer Immunol Immunother 48(2–3):118–122

    Article  PubMed  CAS  Google Scholar 

  • Maloy KJ, Erdmann I, Basch V, Sierro S, Kramps TA, Zinkernagel RM, Oehen S, Kundig TM (2001) Intralymphatic immunization enhances DNA vaccination. Proc Natl Acad Sci USA 98(6):3299–3303

    Article  PubMed  CAS  Google Scholar 

  • Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF (2008) Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol 38(5):1404–1413

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Gomez JM, Johansen P, Erdmann I, Senti G, Crameri R, Kundig TM (2009a) Intralymphatic injections as a new administration route for allergen-specific immunotherapy. Int Arch Allergy Immunol 150(1):59–65

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Gomez JM, Johansen P, Rose H, Steiner M, Senti G, Rhyner C, Crameri R, Kundig TM (2009b) Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy. Allergy 64(1):172–178

    Article  PubMed  CAS  Google Scholar 

  • Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, Koivikko A, Koller DY, Niggemann B, Norberg LA, Urbanek R, Valovirta E, Wahn U (2002) Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 109(2):251–256

    Article  PubMed  Google Scholar 

  • Morse MA, Coleman RE, Akabani G, Niehaus N, Coleman D, Lyerly HK (1999) Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res 59(1):56–58

    PubMed  CAS  Google Scholar 

  • Nilsson BO, Svalander PC, Larsson A (1987) Immunization of mice and rabbits by intrasplenic deposition of nanogram quantities of protein attached to Sepharose beads or nitrocellulose paper strips. J Immunol Methods 99(1):67–75

    Article  PubMed  CAS  Google Scholar 

  • Norman PS (2004) Immunotherapy: 1999–2004. J Allergy Clin Immunol 113(6):1013–1023; quiz 1024

    Article  PubMed  CAS  Google Scholar 

  • Ochsenbein AF, Sierro S, Odermatt B, Pericin M, Karrer U, Hermans J, Hemmi S, Hengartner H, Zinkernagel RM (2001) Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 411(6841):1058–1064

    Article  PubMed  CAS  Google Scholar 

  • Pajno GB, Barberio G, De Luca F, Morabito L, Parmiani S (2001) Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. Clin Exp Allergy 31(9):1392–1397

    Article  PubMed  CAS  Google Scholar 

  • Pierson-Mullany LK, Jackola D, Blumenthal M, Rosenberg A (2000) Altered allergen binding capacities of Amb a 1-specific IgE and IgG4 from ragweed-sensitive patients receiving immunotherapy. Ann Allergy Asthma Immunol 84(2):241–243

    Article  PubMed  CAS  Google Scholar 

  • Quillien V, Moisan A, Carsin A, Lesimple T, Lefeuvre C, Adamski H, Bertho N, Devillers A, Leberre C, Toujas L (2005) Biodistribution of radiolabelled human dendritic cells injected by various routes. Eur J Nucl Med Mol Imag 32(7):731–741

    Article  CAS  Google Scholar 

  • Ribas A, Weber JS, Chmielowski B, Comin-Anduix B, Lu D, Douek M, Ragavendra N, Raman S, Seja E, Rosario D, Miles S, Diamond DC, Qiu Z, Obrocea M, Bot A (2011). Intra-lymph node prime-boost vaccination against Melan A and tyrosinase for the treatment of metastatic melanoma: results of a phase 1 clinical trial. Clin Cancer Res 17(9):2987-2996

    Google Scholar 

  • Rhyner C, Kundig T, Akdis CA, Crameri R (2007) Targeting the MHC II presentation pathway in allergy vaccine development. Biochem Soc Trans 35(Pt 4):833–834

    PubMed  CAS  Google Scholar 

  • Rosenberg SA, Yang JC, Restifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nat Med 10(9):909–915

    Article  PubMed  CAS  Google Scholar 

  • Scheel B, Aulwurm S, Probst J, Stitz L, Hoerr I, Rammensee HG, Weller M, Pascolo S (2006) Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA. Eur J Immunol 36(10):2807–2816

    Article  PubMed  CAS  Google Scholar 

  • Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wuthrich B, Crameri R, Graf N, Johansen P, Kundig TM (2008) Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci USA 105(46):17908–17912

    Article  PubMed  CAS  Google Scholar 

  • Senti G, Johansen P, Kundig TM (2009) Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol 9(6):537–543

    Article  PubMed  Google Scholar 

  • Sigel MB, Sinha YN, VanderLaan WP (1983) Production of antibodies by inoculation into lymph nodes. Methods Enzymol 93:3–12

    Article  PubMed  CAS  Google Scholar 

  • Smith KA, Tam VL, Wong RM, Pagarigan RR, Meisenburg BL, Joea DK, Liu X, Sanders C, Diamond D, Kundig TM, Qiu Z, Bot A (2009) Enhancing DNA vaccination by sequential injection of lymph nodes with plasmid vectors and peptides. Vaccine 27(19):2603–2615

    Article  PubMed  CAS  Google Scholar 

  • Smith KA, Qiu Z, Wong R, Tam VL, Tam BL, Joea DK, Quach A, Liu X, Pold M, Malyankar UM, Bot A (2011) Multivalent immunity targeting tumor-associated antigens by intra-lymph node DNA-prime, peptide-boost vaccination. Cancer Gene Ther 18(1):63–76

    Article  PubMed  CAS  Google Scholar 

  • Stewart GE II, Lockey RF (1992) Systemic reactions from allergen immunotherapy. J Allergy Clin Immunol 90(4 Pt 1):567–578

    Article  PubMed  Google Scholar 

  • Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF (2004) Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. J Immunol 172(3):1777–1785

    PubMed  CAS  Google Scholar 

  • Tagawa ST, Lee P, Snively J, Boswell W, Ounpraseuth S, Lee S, Hickingbottom B, Smith J, Johnson D, Weber JS (2003) Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with stage IV melanoma. Cancer 98(1):144–154

    Article  PubMed  CAS  Google Scholar 

  • The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee (1998) Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 351(9111):1225–1232

    Google Scholar 

  • Thomas R, Chambers M, Boytar R, Barker K, Cavanagh LL, MacFadyen S, Smithers M, Jenkins M, Andersen J (1999) Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy. Melanoma Res 9(5):474–481

    Article  PubMed  CAS  Google Scholar 

  • Till SJ, Francis JN, Nouri-Aria K, Durham SR (2004) Mechanisms of immunotherapy. J Allergy Clin Immunol 113(6):1025–1034, quiz 1035

    Article  PubMed  CAS  Google Scholar 

  • Varney VA, Gaga M, Frew AJ, Aber VR, Kay AB, Durham SR (1991) Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs. BMJ 302(6771):265–269

    Article  PubMed  CAS  Google Scholar 

  • Verlato G, Corsico A, Villani S, Cerveri I, Migliore E, Accordini S, Carolei A, Piccioni P, Bugiani M, Lo Cascio V, Marinoni A, Poli A, de Marco R (2003) Is the prevalence of adult asthma and allergic rhinitis still increasing? results of an Italian study. J Allergy Clin Immunol 111(6):1232–1238

    Article  PubMed  Google Scholar 

  • Vissers JL, van Esch BC, Hofman GA, Kapsenberg ML, Weller FR, van Oosterhout AJ (2004) Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model. J Allergy Clin Immunol 113(6):1204–1210

    Article  PubMed  CAS  Google Scholar 

  • von Beust BR, Johansen P, Smith KA, Bot A, Storni T, Kundig TM (2005) Improving the therapeutic index of CpG oligodeoxynucleotides by intralymphatic administration. Eur J Immunol 35(6):1869–1876

    Article  Google Scholar 

  • Weber J, Boswell W, Smith J, Hersh E, Snively J, Diaz M, Miles S, Liu X, Obrocea M, Qiu Z, Bot A (2008) Phase 1 trial of intranodal injection of a Melan-A/MART-1 DNA plasmid vaccine in patients with stage IV melanoma. J Immunother 31(2):215–223

    Article  PubMed  CAS  Google Scholar 

  • Weide B, Carralot JP, Reese A, Scheel B, Eigentler TK, Hoerr I, Rammensee HG, Garbe C, Pascolo S (2008) Results of the first phase I/II clinical vaccination trial with direct injection of mRNA. J Immunother 31(2):180–188

    Article  PubMed  CAS  Google Scholar 

  • Weide B, Pascolo S, Scheel B, Derhovanessian E, Pflugfelder A, Eigentler TK, Pawelec G, Hoerr I, Rammensee HG, Garbe C (2009) Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. J Immunother 32(5):498–507

    Article  PubMed  CAS  Google Scholar 

  • Wong RM, Smith KA, Tam VL, Pagarigan RR, Meisenburg BL, Quach AM, Carrillo MA, Qiu Z, Bot AI (2009) TLR-9 signaling and TCR stimulation co-regulate CD8(+) T cell-associated PD-1 expression. Immunol Lett 127(1):60–67

    Article  PubMed  CAS  Google Scholar 

  • Wuthrich B, Schindler C, Medici TC, Zellweger JP, Leuenberger P (1996) IgE levels, atopy markers and hay fever in relation to age, sex and smoking status in a normal adult Swiss population. SAPALDIA (Swiss study on air pollution and lung diseases in adults) team. Int Arch Allergy Immunol 111(4):396–402

    Article  PubMed  CAS  Google Scholar 

  • Zinkernagel RM (2000) Localization dose and time of antigens determine immune reactivity. Semin Immunol 12(3):163–171; discussion 257–344

    Article  PubMed  CAS  Google Scholar 

  • Zinkernagel RM, Ehl S, Aichele P, Oehen S, Kundig T, Hengartner H (1997) Antigen localisation regulates immune responses in a dose-and time-dependent fashion: a geographical view of immune reactivity. Immunol Rev 156:199–209

    Article  PubMed  CAS  Google Scholar 

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Kündig, T.M., Bot, A., Senti, G. (2012). Intralymphatic Vaccination. In: Thalhamer, J., Weiss, R., Scheiblhofer, S. (eds) Gene Vaccines. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0439-2_10

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