Skip to main content
SpringerLink
Log in
Book cover

Influenza Pathogenesis and Control - Volume II pp 343–369Cite as

Skin Immunization with Influenza Vaccines

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 386))

Abstract

Problems with existing influenza vaccines include the strain specificity of the immune response, resulting in the need for frequent reformulation in response to viral antigenic drift. Even in years when the same influenza strains are prevalent, the duration of immunity is limited, and results in the need for annual revaccination. The immunogenicity of the present split or subunit vaccines is also lower than that observed with whole inactivated virus, and the vaccines are not very effective in high risk groups such as the young or the elderly. Vaccine coverage is incomplete, due in part to concerns about the use of hypodermic needles for delivery. Alternative approaches for vaccination are being developed which address many of these concerns. Here we review new approaches which focus on skin immunization, including the development of needle-free delivery systems which use stable dry formulations and induce stronger and longer-lasting immune responses.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abdelsadik A, Trad A (2011) Toll-like receptors on the fork roads between innate and adaptive immunity. Hum Immunol 72:1188–1193. doi:10.1016/j.humimm.2011.08.015

    Article  CAS  PubMed  Google Scholar 

  • Alarcon JB, Hartley AW, Harvey NG, Mikszta JA (2007) Preclinical evaluation of microneedle technology for intradermal delivery of influenza vaccines. Clin Vaccine Immunol 14:375–381. doi:10.1128/CVI.00387-06

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Albrecht CM, Sweitzer NK, Johnson MR, Vardeny O (2014) Lack of persistence of influenza vaccine antibody titers in patients with heart failure. J Card Fail 20:105–109. doi:10.1016/j.cardfail.2013.12.008

    Article  CAS  PubMed  Google Scholar 

  • Ansaldi F, Valle L, de Florentiis D, Parodi V, Murdaca G, Bruzzone B, Durando P, Setti M, Icardi G (2012) Phase 4 randomized trial of intradermal low-antigen-content inactivated influenza vaccine versus standard-dose intramuscular vaccine in HIV-1-infected adults. Hum Vaccin Immunother 8:1048–1052. doi:10.4161/hv.20347

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Atkinson WL, Pickering LK, Schwartz B, Weniger BG, Iskander JK, Watson JC (2002) General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR Recomm Rep 51:1–35

    PubMed  Google Scholar 

  • Auewarakul P, Kositanont U, Sornsathapornkul P, Tothong P, Kanyok R, Thongcharoen P (2007) Antibody responses after dose-sparing intradermal influenza vaccination. Vaccine 25:659–63. doi:10.1016/j.vaccine.2006.08.026

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    Article  CAS  PubMed  Google Scholar 

  • Belshe RB, Newman FK, Cannon J, Duane C, Treanor J, Van Hoecke C, Howe BJ, Dubin G (2004) Serum antibody responses after intradermal vaccination against influenza. N Engl J Med 351:2286–94. doi:10.1056/NEJMoa043555

  • Belshe RB, Newman FK, Wilkins K, Graham IL, Babusis E, Ewell M, Frey SE (2007) Comparative immunogenicity of trivalent influenza vaccine administered by intradermal or intramuscular route in healthy adults. Vaccine 25:6755–6763. doi:10.1016/j.vaccine.2007.06.066

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beran J, Ambrozaitis A, Laiskonis A, Mickuviene N, Bacart P, Calozet Y, Demanet E, Heijmans S, Van Belle P, Weber F, Salamand C (2009) Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial. BMC Med 7:13. doi:10.1186/1741-7015-7-13

  • Boger WP, Liu OC (1957) Subcutaneous and intradermal vaccination with Asian influenza vaccine. J Am Med Assoc 165:1687–1689

    Article  CAS  PubMed  Google Scholar 

  • Bragstad K, Martel CJ, Thomsen JS, Jensen KL, Nielsen LP, Aasted B, Fomsgaard A (2011) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades. Influenza Other Respir Viruses 5:13–23. doi:10.1111/j.1750-2659.2010.00177.x

    Article  CAS  PubMed  Google Scholar 

  • Brown H, Kasel JA, Freeman DM, Moise LD, Grose NP, Couch RB (1977) The immunizing effect of influenza A/New Jersey/76 (Hsw1N1) virus vaccine administered intradermally and intramuscularly to adults. J Infect Dis 136(Suppl):S466–471

    Article  PubMed  Google Scholar 

  • Bruyn HB, Meiklejohn G, Brainerd H (1949a) Influenza vaccine; a study of serologic responses and incidence of reactions following subcutaneous and intradermal inoculation. Am J Dis Child 77:149–163

    Article  CAS  PubMed  Google Scholar 

  • Bruyn HB, Meiklejohn G, Brainerd HD (1949b) Influenza vaccination; a comparison of antibody response obtained by various methods of administration. J Immunol 62:1–11

    CAS  PubMed  Google Scholar 

  • Chen D, Erickson CA, Endres RL, Periwal SB, Chu Q, Shu C, Maa YF, Payne LG (2001a) Adjuvantation of epidermal powder immunization. Vaccine 19:2908–2917

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Weis KF, Chu Q, Erickson C, Endres R, Lively CR, Osorio J, Payne LG (2001b) Epidermal powder immunization induces both cytotoxic T-lymphocyte and antibody responses to protein antigens of influenza and hepatitis B viruses. J Virol 75:11630–11640

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen D, Endres R, Maa YF, Kensil CR, Whitaker-Dowling P, Trichel A, Youngner JS, Payne LG (2003) Epidermal powder immunization of mice and monkeys with an influenza vaccine. Vaccine 21:2830–2836

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Burger M, Chu Q, Endres R, Zuleger C, Dean H, Payne LG (2004) Epidermal powder immunization: cellular and molecular mechanisms for enhancing vaccine immunogenicity. Virus Res 103:147–153. doi:10.1016/j.virusres.2004.02.027

    Article  CAS  PubMed  Google Scholar 

  • Choi HJ, Yoo DG, Bondy BJ, Quan FS, Compans RW, Kang SM, Prausnitz MR (2012) Stability of influenza vaccine coated onto microneedles. Biomaterials 33:3756–3769. doi:10.1016/j.biomaterials.2012.01.054

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Choi HJ, Bondy BJ, Yoo DG, Compans RW, Kang SM, Prausnitz MR (2013) Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles. J Control Release 166:159–171. doi:10.1016/j.jconrel.2012.12.002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Combadiere B, Vogt A, Mahe B, Costagliola D, Hadam S, Bonduelle O, Sterry W, Staszewski S, Schaefer H, van der Werf S, Katlama C, Autran B, Blume-Peytavi U (2010) Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial. PLoS One 5:e10818. doi:10.1371/journal.pone.0010818

    Article  PubMed Central  PubMed  Google Scholar 

  • Dean HJ, Chen D (2004) Epidermal powder immunization against influenza. Vaccine 23:681–686. doi:10.1016/j.vaccine.2004.06.041

    Article  CAS  PubMed  Google Scholar 

  • del Pilar Martin M, Seth S, Koutsonanos DG, Jacob J, Compans RW, Skountzou I (2010) Adjuvanted influenza vaccine administered intradermally elicits robust long-term immune responses that confer protection from lethal challenge. PLoS One 5:e10897. doi:10.1371/journal.pone.0010897

    Article  Google Scholar 

  • del Pilar Martin M, Weldon WC, Zarnitsyn VG, Koutsonanos DG, Akbari H, Skountzou I, Jacob J, Prausnitz MR, Compans RW (2012) Local response to microneedle-based influenza immunization in the skin. MBio 3:e00012–12. doi:10.1128/mBio.00012-12

    Google Scholar 

  • Depelsenaire AC, Meliga SC, McNeilly CL, Pearson FE, Coffey JW, Haigh OL, Flaim CJ, Frazer IH, Kendall MA (2014) Colocalization of cell death with antigen deposition in skin enhances vaccine immunogenicity. J Invest Dermatol. doi:10.1038/jid.2014.174

    PubMed  Google Scholar 

  • Ding Z, Verbaan FJ, Bivas-Benita M, Bungener L, Huckriede A, van den Berg DJ, Kersten G, Bouwstra JA (2009) Microneedle arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice. J Control Release 136:71–78. doi:10.1016/j.jconrel.2009.01.025

    Article  CAS  PubMed  Google Scholar 

  • Dupasquier M, Stoitzner P, van Oudenaren A, Romani N, Leenen PJ (2004) Macrophages and dendritic cells constitute a major subpopulation of cells in the mouse dermis. J Invest Dermatol 123:876–879. doi:10.1111/j.0022-202X.2004.23427.x

    Article  CAS  PubMed  Google Scholar 

  • FaDA (FDA) (2011) FDA updated communication on use of jet injectors with inactivated influenza vaccines. Food and Drug Administration, Washington, DC

    Google Scholar 

  • Fernando GJ, Chen X, Prow TW, Crichton ML, Fairmaid EJ, Roberts MS, Frazer IH, Brown LE, Kendall MA (2010) Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model. PLoS One 5:e10266. doi:10.1371/journal.pone.0010266

    Article  PubMed Central  PubMed  Google Scholar 

  • Fernando GJ, Chen X, Primiero CA, Yukiko SR, Fairmaid EJ, Corbett HJ, Frazer IH, Brown LE, Kendall MA (2012) Nanopatch targeted delivery of both antigen and adjuvant to skin synergistically drives enhanced antibody responses. J Control Release 159:215–221. doi:10.1016/j.jconrel.2012.01.030

    Article  CAS  PubMed  Google Scholar 

  • Francis T, Magill TP (1937) The antibody response of human subjects vaccinated with the virus of human influenza. J Exp Med 65:251–259

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Frech SA, Kenney RT, Spyr CA, Lazar H, Viret JF, Herzog C, Gluck R, Glenn GM (2005) Improved immune responses to influenza vaccination in the elderly using an immunostimulant patch. Vaccine 23:946–950. doi:10.1016/j.vaccine.2004.06.036

    Article  CAS  PubMed  Google Scholar 

  • Frolov VG, Seid RC Jr, Odutayo O, Al-Khalili M, Yu J, Frolova OY, Vu H, Butler BA, Look JL, Ellingsworth LR, Glenn GM (2008) Transcutaneous delivery and thermostability of a dry trivalent inactivated influenza vaccine patch. Influenza Other Respir Viruses 2:53–60. doi:10.1111/j.1750-2659.2008.00040.x

    Article  CAS  PubMed  Google Scholar 

  • Fynan EF, Robinson HL, Webster RG (1993a) Use of DNA encoding influenza hemagglutinin as an avian influenza vaccine. DNA Cell Biol 12:785–789

    Article  CAS  PubMed  Google Scholar 

  • Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL (1993b) DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci USA 90:11478–11482

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Garg S, Hoelscher M, Belser JA, Wang C, Jayashankar L, Guo Z, Durland RH, Katz JM, Sambhara S (2007) Needle-free skin patch delivery of a vaccine for a potentially pandemic influenza virus provides protection against lethal challenge in mice. Clin Vaccine Immunol 14:926–928. doi:10.1128/CVI.00450-06

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gill HS, Denson DD, Burris BA, Prausnitz MR (2008) Effect of microneedle design on pain in human volunteers. Clin J Pain 24:585–594. doi:10.1097/AJP.0b013e31816778f9, 00002508-200809000-00005

  • Giudice EL, Campbell JD (2006) Needle-free vaccine delivery. Adv Drug Deliv Rev 58:68–89

    Article  CAS  PubMed  Google Scholar 

  • Glazier MM, Benenson AS, Wheeler RE (1956) Active immunization with influenza virus A and B in infants and children. Pediatrics 17:482–488

    CAS  PubMed  Google Scholar 

  • Glenn GM, Kenney RT, Ellingsworth LR, Frech SA, Hammond SA, Zoeteweij JP (2003) Transcutaneous immunization and immunostimulant strategies: capitalizing on the immunocompetence of the skin. Expert Rev Vaccines 2:253–267

    Article  CAS  PubMed  Google Scholar 

  • Guebre-Xabier M, Hammond SA, Ellingsworth LR, Glenn GM (2004) Immunostimulant patch enhances immune responses to influenza virus vaccine in aged mice. J Virol 78:7610–7618. doi:10.1128/JVI.78.14.7610-7618.2004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hilleman MR, Flatley FJ, Anderson SA, Luecking ML, Levinson DJ (1958) Antibody response in volunteers to Asian influenza vaccine. J Am Med Assoc 166:1134–1140

    Article  CAS  PubMed  Google Scholar 

  • Hoft DF, Blazevic A, Abate G, Hanekom WA, Kaplan G, Soler JH, Weichold F, Geiter L, Sadoff JC, Horwitz MA (2008) A new recombinant bacille Calmette-Guerin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers. J Infect Dis 198:1491–1501. doi:10.1086/592450

    Article  PubMed Central  PubMed  Google Scholar 

  • Hung IF, Levin Y, To KK, Chan KH, Zhang AJ, Li P, Li C, Xu T, Wong TY, Yuen KY (2012) Dose sparing intradermal trivalent influenza (2010/2011) vaccination overcomes reduced immunogenicity of the 2009 H1N1 strain. Vaccine 30:6427–6435. doi:10.1016/j.vaccine.2012.08.014

    Article  CAS  PubMed  Google Scholar 

  • Icardi G, Orsi A, Ceravolo A, Ansaldi F (2012) Current evidence on intradermal influenza vaccines administered by Soluvia licensed micro injection system. Hum Vaccin Immunother 8:67–75. doi:10.4161/hv.8.1.18419

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ismach A (1960) Jet injector. http://www.scienceheroes.com/index.php?option=com_content&view=article&id=166&Itemid=165

  • Itano AA, McSorley SJ, Reinhardt RL, Ehst BD, Ingulli E, Rudensky AY, Jenkins MK (2003) Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity 19:47–57

    Article  CAS  PubMed  Google Scholar 

  • Jackson LA, Austin G, Chen RT, Stout R, DeStefano F, Gorse GJ, Newman FK, Yu O, Weniger BG, Vaccine Safety Datalink Study G (2001) Safety and immunogenicity of varying dosages of trivalent inactivated influenza vaccine administered by needle-free jet injectors. Vaccine 19:4703–4709

    Google Scholar 

  • Jones S, Evans K, McElwaine-Johnn H, Sharpe M, Oxford J, Lambkin-Williams R, Mant T, Nolan A, Zambon M, Ellis J, Beadle J, Loudon PT (2009) DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial. Vaccine 27:2506–2512. doi:10.1016/j.vaccine.2009.02.061

    Article  CAS  PubMed  Google Scholar 

  • Kim YC, Quan FS, Compans RW, Kang SM, Prausnitz MR (2010a) Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. J Control Release 142:187–95. doi: 10.1016/j.jconrel.2009.10.013, S0168-3659(09)00708-1

  • Kim YC, Quan FS, Compans RW, Kang SM, Prausnitz MR (2010b) Formulation of microneedles coated with influenza virus-like particle vaccine. AAPS PharmSciTech 11:1193–1201. doi:10.1208/s12249-010-9471-3

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim YC, Quan FS, Compans RW, Kang SM, Prausnitz MR (2011) Stability kinetics of influenza vaccine coated onto microneedles during drying and storage. Pharm Res 28:135–144. doi:10.1007/s11095-010-0134-6

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim YC, Jarrahian C, Zehrung D, Mitragotri S, Prausnitz MR (2012) Delivery systems for intradermal vaccination. Curr Top Microbiol Immunol 351:77–112. doi:10.1007/82_2011_123

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim YK, Eun BW, Kim NH, Kang EK, Lee BS, Kim DH, Lim JS (2013) Comparison of immunogenicity and reactogenicity of split versus subunit influenza vaccine in Korean children aged 6-35 months. Scand J Infect Dis 45:460–468. doi:10.3109/00365548.2012.755267

    Article  PubMed  Google Scholar 

  • Kommareddy S, Baudner BC, Oh S, Kwon SY, Singh M, O’Hagan DT (2012) Dissolvable microneedle patches for the delivery of cell-culture-derived influenza vaccine antigens. J Pharm Sci 101:1021–1027. doi:10.1002/jps.23019

    Article  CAS  PubMed  Google Scholar 

  • Kommareddy S, Baudner BC, Bonificio A, Gallorini S, Palladino G, Determan AS, Dohmeier DM, Kroells KD, Sternjohn JR, Singh M, Dormitzer PR, Hansen KJ, O’Hagan DT (2013) Influenza subunit vaccine coated microneedle patches elicit comparable immune responses to intramuscular injection in guinea pigs. Vaccine 31:3435–3441. doi:10.1016/j.vaccine.2013.01.050

    Article  CAS  PubMed  Google Scholar 

  • Koutsonanos DG, del Pilar Martin M, Zarnitsyn VG, Sullivan SP, Compans RW, Prausnitz MR, Skountzou I (2009) Transdermal influenza immunization with vaccine-coated microneedle arrays. PLoS One 4:e4773. doi:10.1371/journal.pone.0004773

    Article  PubMed Central  PubMed  Google Scholar 

  • Koutsonanos DG, del Pilar Martin M, Zarnitsyn VG, Jacob J, Prausnitz MR, Compans RW, Skountzou I (2011) Serological memory and long-term protection to novel H1N1 influenza virus after skin vaccination. J Infect Dis 204:582–591. doi:10.1093/infdis/jir094

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Koutsonanos DG, Vassilieva EV, Stavropoulou A, Zarnitsyn VG, Esser ES, Taherbhai MT, Prausnitz MR, Compans RW, Skountzou I (2012) Delivery of subunit influenza vaccine to skin with microneedles improves immunogenicity and long-lived protection. Sci Rep 2:357. doi:10.1038/srep00357

    Article  PubMed Central  PubMed  Google Scholar 

  • Kunzi V, Klap JM, Seiberling MK, Herzog C, Hartmann K, Kursteiner O, Kompier R, Grimaldi R, Goudsmit J (2009) Immunogenicity and safety of low dose virosomal adjuvanted influenza vaccine administered intradermally compared to intramuscular full dose administration. Vaccine 27:3561–3567. doi:10.1016/j.vaccine.2009.03.062

    Article  PubMed  Google Scholar 

  • Laurent PE, Bonnet S, Alchas P, Regolini P, Mikszta JA, Pettis R, Harvey NG (2007) Evaluation of the clinical performance of a new intradermal vaccine administration technique and associated delivery system. Vaccine 25:8833–8842. doi:10.1016/j.vaccine.2007.10.020, S0264-410X(07)01156-5

  • Locati M, Allavena P, Sozzani S, Mantovanii A (2000) Shaping and tuning of the chemokine system by regulation of receptor expression and signaling: dendritic cells as a paradigm. J Neuroimmunol 107:174–177

    Article  CAS  PubMed  Google Scholar 

  • Mantoux C (1909) Tuberculin intradermo reactions in the treatment of tuberculosis: Intradermi-tuberculisation. Comptes Rendus Hebdomadaires Des Seances De L Academie Des Sci 148:996–998

    Google Scholar 

  • Matsuo K, Hirobe S, Yokota Y, Ayabe Y, Seto M, Quan YS, Kamiyama F, Tougan T, Horii T, Mukai Y, Okada N, Nakagawa S (2012) Transcutaneous immunization using a dissolving microneedle array protects against tetanus, diphtheria, malaria, and influenza. J Control Release 160:495–501. doi:10.1016/j.jconrel.2012.04.001

    Article  CAS  PubMed  Google Scholar 

  • Moylett EH, Hanson IC (2004) Mechanistic actions of the risks and adverse events associated with vaccine administration. J Allergy Clin Immunol 114:1010–20; quiz 1021

    Google Scholar 

  • Norman JJ, Arya JM, McClain MA, Frew PM, Meltzer MI, Prausnitz MR (2014) Microneedle patches: usability and acceptability for self-vaccination againt influenza. Vaccine. 32(16):1856–62. doi: 10.1016/j.vaccine.2014.01.076. Epub 2014 Feb 11. PMID: 24530146 [PubMed - in process]

  • Ogunremi O, Pasick J, Berhane Y (2013) Needle-free delivery of an inactivated avian influenza H5N3 virus vaccine elicits potent antibody responses in chickens. Can J Vet Res 77:309–313

    CAS  PubMed Central  PubMed  Google Scholar 

  • Osterholm MT, Kelley NS, Sommer A, Belongia EA (2012) Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12:36–44. doi:10.1016/S1473-3099(11)70295-X

    Article  PubMed  Google Scholar 

  • Pearton M, Kang SM, Song JM, Anstey AV, Ivory M, Compans RW, Birchall JC (2010a) Changes in human Langerhans cells following intradermal injection of influenza virus-like particle vaccines. PLoS One 5:e12410. doi:10.1371/journal.pone.0012410

    Article  PubMed Central  PubMed  Google Scholar 

  • Pearton M, Kang SM, Song JM, Kim YC, Quan FS, Anstey A, Ivory M, Prausnitz MR, Compans RW, Birchall JC (2010b) Influenza virus-like particles coated onto microneedles can elicit stimulatory effects on Langerhans cells in human skin. Vaccine 28:6104-13. doi: 10.1016/j.vaccine.2010.05.055, S0264-410X(10)00764-4

  • Pearton M, Pirri D, Kang SM, Compans RW, Birchall JC (2013) Host responses in human skin after conventional intradermal injection or microneedle administration of virus-like-particle influenza vaccine. Adv Healthc Mater 2:1401–1410. doi:10.1002/adhm.201300006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Quan FS, Kim YC, Yoo DG, Compans RW, Prausnitz MR, Kang SM (2009) Stabilization of influenza vaccine enhances protection by microneedle delivery in the mouse skin. PLoS One 4:e7152. doi:10.1371/journal.pone.0007152

    Article  PubMed Central  PubMed  Google Scholar 

  • Quan FS, Kim YC, Compans RW, Prausnitz MR, Kang SM (2010a) Dose sparing enabled by skin immunization with influenza virus-like particle vaccine using microneedles. J Control Release 147:326–332. doi:10.1016/j.jconrel.2010.07.125

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Quan FS, Kim YC, Vunnava A, Yoo DG, Song JM, Prausnitz MR, Compans RW, Kang SM (2010b) Intradermal vaccination with influenza virus-like particles by using microneedles induces protection superior to that with intramuscular immunization. J Virol 84:7760-9. doi:10.1128/JVI.01849-09JVI.01849-09

  • Quan FS, Kim YC, Song JM, Hwang HS, Compans RW, Prausnitz MR, Kang SM (2013) Long-term protective immunity from an influenza virus-like particle vaccine administered with a microneedle patch. Clin Vaccine Immunol. doi:10.1128/CVI.00251-13

    PubMed Central  PubMed  Google Scholar 

  • Rao S, Kong WP, Wei CJ, Yang ZY, Nason M, Styles D, DeTolla LJ, Panda A, Sorrell EM, Song H, Wan H, Ramirez-Nieto GC, Perez D, Nabel GJ (2008) Multivalent HA DNA vaccination protects against highly pathogenic H5N1 avian influenza infection in chickens and mice. PLoS One 3:e2432. doi:10.1371/journal.pone.0002432

    Article  PubMed Central  PubMed  Google Scholar 

  • Raphael AP, Prow TW, Crichton ML, Chen X, Fernando GJ, Kendall MA (2010) Targeted, needle-free vaccinations in skin using multilayered, densely-packed dissolving microprojection arrays. Small 6:1785–1793. doi:10.1002/smll.201000326

    Article  CAS  PubMed  Google Scholar 

  • Riedel S (2005) Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent) 18:21–25

    Google Scholar 

  • Romani N, Tschachler E, Schuler G, Aberer W, Ceredig R, Elbe A, Wolff K, Fritsch PO, Stingl G (1985) Morphological and phenotypical characterization of bone marrow-derived dendritic Thy-1-positive epidermal cells of the mouse. J Invest Dermatol 85:91s–95s

    Article  CAS  PubMed  Google Scholar 

  • Romani N, Flacher V, Tripp CH, Sparber F, Ebner S, Stoitzner P (2012) Targeting skin dendritic cells to improve intradermal vaccination. Curr Top Microbiol Immunol 351:113–138. doi:10.1007/82_2010_118

    CAS  PubMed  Google Scholar 

  • Sencer DJ, Millar JD (2006) Reflections on the 1976 swine flu vaccination program. Emerg Infect Dis 12:29–33. doi:10.3201/eid1201.051007

    Article  PubMed Central  PubMed  Google Scholar 

  • Skountzou I, Kang SM (2009) Transcutaneous immunization with influenza vaccines. Curr Top Microbiol Immunol 333:347–368. doi:10.1007/978-3-540-92165-3_17

    CAS  PubMed  Google Scholar 

  • Skountzou I, Quan FS, Jacob J, Compans RW, Kang SM (2006) Transcutaneous immunization with inactivated influenza virus induces protective immune responses. Vaccine 24:6110–6119. doi:10.1016/j.vaccine.2006.05.014

    Article  CAS  PubMed  Google Scholar 

  • Song JM, Kim YC, Barlow PG, Hossain MJ, Park KM, Donis RO, Prausnitz MR, Compans RW, Kang SM (2010a) Improved protection against avian influenza H5N1 virus by a single vaccination with virus-like particles in skin using microneedles. Antiviral Res 88:244–247. doi:10.1016/j.antiviral.2010.09.001

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Song JM, Kim YC, Lipatov AS, Pearton M, Davis CT, Yoo DG, Park KM, Chen LM, Quan FS, Birchall JC, Donis RO, Prausnitz MR, Compans RW, Kang SM (2010b) Microneedle delivery of H5N1 influenza virus-like particles to the skin induces long-lasting B- and T-cell responses in mice. Clin Vaccine Immunol 17:1381–1389. doi:10.1128/CVI.00100-10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Song JM, Kim YC, O E Compans RW, Prausnitz RW, Kang (2012) DNA vaccination in the skin using microneedles improves protection against influenza. Mol Ther 20:1472–1480. doi:10.1038/mt.2012.69

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sozzani S, Allavena P, Vecchi A, Mantovani A (2000) Chemokines and dendritic cell traffic. J Clin Immunol 20:151–260

    Article  CAS  PubMed  Google Scholar 

  • Sparber F, Tripp CH, Hermann M, Romani N, Stoitzner P (2010) Langerhans cells and dermal dendritic cells capture protein antigens in the skin: possible targets for vaccination through the skin. Immunobiology 215:770–779. doi:10.1016/j.imbio.2010.05.014

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sullivan SP, Koutsonanos DG, del Pilar Martin M, Lee JW, Zarnitsyn V, Choi SO, Murthy N, Compans RW, Skountzou I, Prausnitz MR (2010) Dissolving polymer microneedle patches for influenza vaccination. Nat Med 16:915–920. doi:10.1038/nm.2182

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tauraso NM, Gleckman R, Pedreira FA, Sabbaj J, Yahwak R, Madoff MA (1969) Effect of dosage and route of inoculation upon antigenicity of inactivated influenza virus vaccine (Hong Kong strain) in man. Bull World Health Organ 41:507–516

    CAS  PubMed Central  PubMed  Google Scholar 

  • Teunissen MBM (2012) Intradermal Immunization. Current topics in microbiology and immunology, vol 351

    Google Scholar 

  • Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S (2000) Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12:71–81

    Article  CAS  PubMed  Google Scholar 

  • Van Damme P, Oosterhuis-Kafeja F, Van der Wielen M, Almagor Y, Sharon O, Levin Y (2009) Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine 27:454–459. doi:10.1016/j.vaccine.2008.10.077

    Article  PubMed  Google Scholar 

  • Van Gelder DW, Greenspan FS, Dufresne NE (1947) Influenza vaccination; comparison of intracutaneous and subcutaneous methods. U S Nav Med Bull 47:197–206

    Google Scholar 

  • Van Kampen KR, Shi Z, Gao P, Zhang J, Foster KW, Chen DT, Marks D, Elmets CA, Tang DC (2005) Safety and immunogenicity of adenovirus-vectored nasal and epicutaneous influenza vaccines in humans. Vaccine 23:1029–1036. doi:10.1016/j.vaccine.2004.07.043

    Article  PubMed  Google Scholar 

  • Wang BZ, Gill HS, He C, Ou C, Wang L, Wang YC, Feng H, Zhang H, Prausnitz MR, Compans RW (2014) Microneedle delivery of an M2e-TLR5 ligand fusion protein to skin confers broadly cross-protective influenza immunity. J Control Release 178:1–7. doi:10.1016/j.jconrel.2014.01.002

    Article  CAS  PubMed  Google Scholar 

  • Weir E, Hatch K (2004) Preventing cold chain failure: vaccine storage and handling. Cmaj 171:1050

    Article  PubMed Central  PubMed  Google Scholar 

  • Weldon WC, del Pilar Martin MP, Zarnitsyn V, Wang B, Koutsonanos D, Skountzou I, Prausnitz MR, Compans RW (2011) Microneedle vaccination with stabilized recombinant influenza virus hemagglutinin induces improved protective immunity. Clin Vaccine Immunol 18:647–654. doi:10.1128/CVI.00435-10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weldon WC, Zarnitsyn VG, Esser ES, Taherbhai MT, Koutsonanos DG, Vassilieva EV, Skountzou I, Prausnitz MR, Compans RW (2012) Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine. PLoS One 7:e41501. doi:10.1371/journal.pone.0041501

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weller TH, Cheever FS, Enders JF (1948) Immunologic reactions following the intradermal inoculation of influenza A and B vaccine. Proc Soc Exp Biol Med 67:96–101

    Article  CAS  PubMed  Google Scholar 

  • Weniger BG, Glenn GM (2013) Cutaneous vaccination: antigen delivery into or onto the skin. Vaccine 31:3389–3391. doi:10.1016/j.vaccine.2013.05.048

    Article  CAS  PubMed  Google Scholar 

  • WHO (WHO) (2005) Solutions: Choosing Technologies for Safe Injections. Accessed 2011-05-06 2011

    Google Scholar 

  • Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    Article  CAS  PubMed  Google Scholar 

  • Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, McCausland M, Skountzou I, Hornig M, Lipkin WI, Mehta A, Razavi B, Del Rio C, Zheng NY, Lee JH, Huang M, Ali Z, Kaur K, Andrews S, Amara RR, Wang Y, Das SR, O’Donnell CD, Yewdell JW, Subbarao K, Marasco WA, Mulligan MJ, Compans R, Ahmed R, Wilson PC (2011) Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 208:181–93. doi: 10.1084/jem.20101352, S0166-3542(10)00705-9

  • Yewdell JW, Bennink JR, Smith GL, Moss B (1985) Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci USA 82:1785–1789

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu Q, Zarnitsyn VG, Ye L, Wen Z, Gao Y, Pan L, Skountzou I, Gill HS, Prausnitz MR, Yang C, Compans RW (2009) Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge. Proc Natl Acad Sci USA 106:7968–7973. doi:10.1073/pnas.0812652106

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ms. Erin-Joi Collins for her valuable assistance in the preparation and submission of this manuscript. Research by the authors was supported in part by the U.S. Department of Health and Human Services contract HHSN272201400006C (NIAID Centers of Excellence for Influenza Research and Surveillance) and the National Institutes of Health grant U01EB012495 (M. Prausnitz, PI).

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, CNR Building, 1518 Clifton Road, Atlanta, GA, 30322, USA

    Ioanna Skountzou & Richard W. Compans

Authors
  1. Ioanna Skountzou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard W. Compans
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ioanna Skountzou .

Editor information

Editors and Affiliations

  1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA

    Michael B. A. Oldstone

  2. IDepartment of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA

    Richard W. Compans

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Skountzou, I., Compans, R.W. (2014). Skin Immunization with Influenza Vaccines. In: Oldstone, M., Compans, R. (eds) Influenza Pathogenesis and Control - Volume II. Current Topics in Microbiology and Immunology, vol 386. Springer, Cham. https://doi.org/10.1007/82_2014_407

Download citation

Publish with us

Policies and ethics

Search

Navigation