Skip to main content

Advertisement

SpringerLink
Log in

Lipid-based antigen delivery systems

  • Review
  • Published:
Journal of Pharmaceutical Investigation Aims and scope Submit manuscript

Abstract

Lipid-based carriers, including liposomes and emulsions, have been studied as antigen delivery systems to improve humoral and cellular immune responses. Lipid-based delivery systems have been tailored based on the physicochemical properties of antigens and administration routes. Non-covalent encapsulation or chemical conjugation of antigens onto the surface of nanocarriers has been reported to load high amounts of antigen, protect antigens from degradation, and enhance cellular uptake by immune cells. Moreover, active targeting to antigen-presenting cells can be achieved through surface modification of lipid-based nanostructures. Antigens, which include proteins, peptides and nucleic acids, have been delivered by appropriate lipid-based delivery systems, and antigen-loaded lipid nanoparticles have been shown to cause greater immune responses compared with naked antigens. For in vivo applications, both invasive and non-invasive routes have been adopted for vaccination with antigen-loaded lipid nanocarriers. In this review, we address recent progress, current status, and clinical applications of lipid-based antigen delivery systems.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Alving CR, Beck Z, Matyas GR, Rao M (2016) Liposomal adjuvants for human vaccines. Expert Opin Drug Deliv 25:1–10

    Article  Google Scholar 

  • Barnier-Quer C, Elsharkawy A, Romeijn S, Kros A, Jiskoot W (2013) Adjuvant effect of cationic liposomes for subunit influenza vaccine: influence of antigen loading method, cholesterol and immune modulators. Pharmaceutics 5(3):392–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barouch DH (2008) Challenges in the development of an HIV-1 vaccine. Nature 455:613–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bioley G, Lassus A, Bussat P, Terrettaz J, Tranquart F, Corthésy B (2012) Gas-filled microbubble-mediated delivery of antigen and the induction of immune responses. Biomaterials 33:5935–5946

    Article  CAS  PubMed  Google Scholar 

  • Bioley G, Zehn D, Lassus A, Terrettaz J, Tranquart F, Corthésy B (2013) The effect of vaccines based on ovalbumin coupled to gas-filled microbubbles for reducing infection by ovalbumin-expressing Listeria monocytogenes. Biomaterials 34:5423–5430

    Article  CAS  PubMed  Google Scholar 

  • Bogers WM, Oostermeijer H, Mooij P, Koopman G, Verschoor EJ, Davis D, Ulmer JB, Brito LA, Cu Y, Banerjee K, Otten GR, Burke B, Dey A, Heeney JL, Shen X, Tomaras GD, Labranche C, Montefiori DC, Liao HX, Haynes B, Geall AJ, Barnett SW (2015) Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion. J Infect Dis 211:947–955

    Article  PubMed  Google Scholar 

  • Bovier PA (2008) Epaxal: a virosomal vaccine to prevent hepatitis A infection. Expert Rev Vaccines 7:1141–1150

    Article  CAS  PubMed  Google Scholar 

  • Brito LA, Chan M, Shaw CA, Hekele A, Carsillo T, Schaefer M, Archer J, Seubert A, Otten GR, Beard CW, Dey AK, Lilja A, Valiante NM, Mason PW, Mandl CW, Barnett SW, Dormitzer PR, Ulmer JB, Singh M, O’Hagan DT, Geall AJ (2014) A cationic nanoemulsion for the delivery of next-generation RNA vaccines. Mol Ther 22:2118–2129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carneiro C, Correia A, Collins T, Vilanova M, Pais C, Gomes AC, Real Oliveira ME, Sampaio P (2015) DODAB:monoolein liposomes containing Candida albicans cell wall surface proteins: a novel adjuvant and delivery system. Eur J Pharm Biopharm 89:190–200

    Article  CAS  PubMed  Google Scholar 

  • Chavoshian O, Biari N, Badiee A, Khamesipour A, Abbasi A, Saberi Z, Jalali SA, Jaafari MR (2013) Sphingomyelin liposomes containing soluble Leishmania major antigens induced strong Th2 immune response in BALB/c mice. Iran J Basic Med Sci 16(9):965–972

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen L, Zhu J, Li Y, Lu J, Gao L, Xu H, Fan M, Yang X (2013) Enhanced nasal mucosal delivery and immunogenicity of anti-caries DNA vaccine through incorporation of anionic liposomes in chitosan/DNA complexes. PLoS One 8(8):e71953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • D’Acremont V, Herzog C, Genton B (2006) Immunogenicity and safety of a virosomal hepatitis A vaccine (Epaxal) in the elderly. J Travel Med 13:78–83

    Article  PubMed  Google Scholar 

  • Eskandari F, Talesh GA, Parooie M, Jaafari MR, Khamesipour A, Saberi Z, Abbasi A, Badiee A (2014) immunoliposomes containing soluble Leishmania antigens (SLA) as a novel antigen delivery system in murine model of leishmaniasis. Exp Parasitol 146:78–86

    Article  CAS  PubMed  Google Scholar 

  • Fan Y, Sahdev P, Ochyl LJ, Akerberg J, Moon JJ (2015) Cationic liposome-hyaluronic acid hybrid nanoparticles for intranasal vaccination with subunit antigens. J Control Release 208:121–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Firouzmand H, Badiee A, Khamesipour A, Heravi Shargh V, Alavizadeh SH, Abbasi A, Jaafari MR (2013) Induction of protection against leishmaniasis in susceptible BALB/c mice using simple DOTAP cationic nanoliposomes containing soluble Leishmania antigen (SLA). Acta Trop 128:528–535

    Article  CAS  PubMed  Google Scholar 

  • Ghaffar KA, Giddam AK, Zaman M, Skwarczynski M, Toth I (2014) Liposomes as nanovaccine delivery systems. Curr Top Med Chem 14:1194–1208

    Article  PubMed  Google Scholar 

  • Giddam AK, Zaman M, Skwarczynski M, Toth I (2012) Liposome-based delivery system for vaccine candidates: constructing an effective formulation. Nanomedicine (Lond) 7:1877–1893

    Article  CAS  Google Scholar 

  • Glück R, Mischler R, Brantschen S, Just M, Althaus B, Cryz SJ Jr (1992) Immunopotentiating reconstituted influenza virus virosome vaccine delivery system for immunization against hepatitis A. J Clin Invest 90:2491–2495

    Article  PubMed  PubMed Central  Google Scholar 

  • Herzog C, Hartmann K, Künzi V, Kürsteiner O, Mischler R, Lazar H, Glück R (2009) Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine. Vaccine 27:4381–4387

    Article  CAS  PubMed  Google Scholar 

  • Hjálmsdóttir Á, Bühler C, Vonwil V, Roveri M, Håkerud M, Wäckerle-Men Y, Gander B, Johansen P (2016) Cytosolic delivery of liposomal vaccines by means of the concomitant photosensitization of phagosomes. Mol Pharm. doi:10.1021/acs.molpharmaceut.5b00394

    PubMed  Google Scholar 

  • Hu Y, Zheng H, Huang W, Zhang CA (2014) Novel and efficient nicotine vaccine using nano-lipoplex as a delivery vehicle. Hum Vaccin Immunother 10(1):64–72

    Article  CAS  PubMed  Google Scholar 

  • Kallert S, Zenk SF, Walther P, Grieshober M, Weil T, Stenger S (2015) Liposomal delivery of lipoarabinomannan triggers Mycobacterium tuberculosis specific T-cells. Tuberculosis (Edinb). 95:452–462

    Article  CAS  PubMed  Google Scholar 

  • Lanzi A, Fehres CM, de Gruijl TD, van Kooyk Y, Mastrobattista E (2014) Effects of antigen-expressing immunostimulatory liposomes on chemotaxis and maturation of dendritic cells in vitro and in human skin explants. Pharm Res 31(2):516–526

    Article  CAS  PubMed  Google Scholar 

  • Li P, Chen S, Jiang Y, Jiang J, Zhang Z, Sun X (2013) Dendritic cell targeted liposomes-protamine-DNA complexes mediated by synthetic mannosylated cholesterol as a potential carrier for DNA vaccine. Nanotechnology 24:295101

    Article  PubMed  Google Scholar 

  • Malik B, Gupta RK, Rath G, Goyal AK (2014) Development of pH responsive novel emulsion adjuvant for oral immunization and in vivo evaluation. Eur J Pharm Biopharm 87:589–597

    Article  CAS  PubMed  Google Scholar 

  • Mischler R, Metcalfe IC (2002) Inflexal V a trivalent virosome subunit influenza vaccine: production. Vaccine 20:B17–B23

    Article  CAS  PubMed  Google Scholar 

  • Sahdev P, Ochyl LJ, Moon JJ (2014) Biomaterials for nanoparticle vaccine delivery systems. Pharm Res 31:2563–2582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwendener RA (2014) Liposomes as vaccine delivery systems: a review of the recent advances. Ther Adv Vaccines 2:159–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Senchi K, Matsunaga S, Hasegawa H, Kimura H, Ryo A (2013) Development of oligomannose-coated liposome-based nasal vaccine against human parainfluenza virus type 3. Front Microbiol 4:346

    Article  PubMed  PubMed Central  Google Scholar 

  • Smith DM, Simon JK, Baker JR Jr (2013) Applications of nanotechnology for immunology. Nat Rev Immunol 13:592–605

    Article  CAS  PubMed  Google Scholar 

  • Takagi A, Kobayashi N, Taneichi M, Uchida T, Akatsuka T (2013) Coupling to the surface of liposomes alters the immunogenicity of hepatitis C virus-derived peptides and confers sterile immunity. Biochem Biophys Res Commun 430:183–189

    Article  CAS  PubMed  Google Scholar 

  • Trentini MM, de Oliveira FM, Gaeti MP, Batista AC, Lima EM, Kipnis A, Junqueira-Kipnis AP (2014) Microstructured liposome subunit vaccines reduce lung inflammation and bacterial load after Mycobacterium tuberculosis infection. Vaccine 32(34):4324–4332

    Article  CAS  PubMed  Google Scholar 

  • Tyagi RK, Garg NK, Jadon R, Sahu T, Katare OP, Dalai SK, Awasthi A, Marepally SK (2015) Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P. falciparum surface antigen, MSP-119. Vaccine 33:4630–4638

    Article  CAS  PubMed  Google Scholar 

  • Usonis V, Bakasénas V, Valentelis R, Katiliene G, Vidzeniene D, Herzog C (2003) Antibody titres after primary and booster vaccination of infants and young children with a virosomal hepatitis A vaccine (Epaxal). Vaccine 21:4588–4592

    Article  CAS  PubMed  Google Scholar 

  • Wang HW, Jiang PL, Lin SF, Lin HJ, Ou KL, Deng WP, Lee LW, Huang YY, Liang PH, Liu DZ (2013) Application of galactose-modified liposomes as a potent antigen presenting cell targeted carrier for intranasal immunization. Acta Biomater 9:5681–5688

    Article  CAS  PubMed  Google Scholar 

  • Wang N, Wang T, Zhang M, Chen R, Niu R, Deng Y (2014a) Mannose derivative and lipid A dually decorated cationic liposomes as an effective cold chain free oral mucosal vaccine adjuvant-delivery system. Eur J Pharm Biopharm 88:194–206

    Article  CAS  PubMed  Google Scholar 

  • Wang N, Wang T, Zhang M, Chen R, Deng Y (2014b) Using procedure of emulsification-lyophilization to form lipid A-incorporating cochleates as an effective oral mucosal vaccine adjuvant-delivery system (VADS). Int J Pharm 468:39–49

    Article  CAS  PubMed  Google Scholar 

  • Watarai S, Iwase T, Tajima T, Yuba E, Kono K (2013) Efficiency of pH-sensitive fusogenic polymer-modified liposomes as a vaccine carrier. Sci World J 2013:903234

    Article  Google Scholar 

  • Wilschut J (2009) Influenza vaccines: the virosome concept. Immunol Lett 21(122):118–121

    Article  Google Scholar 

  • Woelbing F, Kostka SL, Moelle K, Belkaid Y, Sunderkoetter C, Verbeek S, Waisman A, Nigg AP, Knop J, Udey MC, Stebut E (2006) Uptake of Leishmania major by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity. J Exp Med 203:177–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong PT, Wang SH, Ciotti S, Makidon PE, Smith DM, Fan Y, Schuler CF 4th, Baker JR Jr (2014) Formulation and characterization of nanoemulsion intranasal adjuvants: effects of surfactant composition on mucoadhesion and immunogenicity. Mol Pharm 11:531–544

    Article  CAS  PubMed  Google Scholar 

  • Zhen Y, Wang N, Gao Z, Ma X, Wei B, Deng Y, Wang T (2015) Multifunctional liposomes constituting microneedles induced robust systemic and mucosal immunoresponses against the loaded antigens via oral mucosal vaccination. Vaccine 33:4330–4340

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work has been financially supported by a Grant from the Korean Health Technology R&D Project (No. HI15C2842), Ministry of Health & Welfare, Republic of Korea. These authors (JY Park, G Shim, MG Kim, and YK Oh) declare that they have no conflict of interest. This article does not contain any studies with human and animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, South Korea

    Joo Yeon Park, Mi-Gyeong Kim, Gayong Shim & Yu-Kyoung Oh

Authors
  1. Joo Yeon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mi-Gyeong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gayong Shim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu-Kyoung Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Gayong Shim or Yu-Kyoung Oh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, J.Y., Kim, MG., Shim, G. et al. Lipid-based antigen delivery systems. Journal of Pharmaceutical Investigation 46, 295–304 (2016). https://doi.org/10.1007/s40005-016-0246-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-016-0246-z

Keywords

Search

Navigation