Skip to main content

Advertisement

SpringerLink
Log in

Physicochemical properties of particulate vaccine adjuvants: their pivotal role in modulating immune responses

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

Abstract

Vaccine adjuvants enhance immunogenic responses of antigens and increase potency of vaccines. Physicochemical properties of particulate vaccine adjuvants namely, particle size, surface charge, hydrophobicity, shape and composition play an important role to determine their activity and potency. Various studies have been done using different types of particulate vaccine adjuvants to correlate their physicochemical properties with immune responses. Generally, change in particle size does not show any trend in modulation of immunogenicity, however, it directly influences on cellular uptake of particles, leading to alteration of cytokine profile and induction of Th1 and/or Th2 responses. Usually, positively charged adjuvant particles undergo higher cellular uptake than negatively charged particles and hydrophobic particles undergo cellular uptake more efficiently than hydrophilic particles. Furthermore, shape and composition of adjuvant particles also influence on immune responses. This review gives an insight into the impact of particle size, surface charge, hydrophobicity, shape and composition of particulate vaccine adjuvants in modulating immune responses.

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

(redrawn and modified from Zhao et al. 2014)

Similar content being viewed by others

References

  • Agarwal R, Singh V, Jurney P, Shi L, Sreenivasan SV, Roy K (2013) Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms. Proc Natl Acad Sci 110:17247–17252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akagi T, Baba M, Akashi M (2012) Biodegradable nanoparticles as vaccine adjuvants and delivery systems: regulation of immune responses by nanoparticle-based vaccine. In: Kunugi S, Yamaoka T (eds) Polymers in nanomedicine. Springer, Berlin, pp 31–64

    Google Scholar 

  • Aucouturier J, Dupuis L, Ganne V (2001) Adjuvants designed for veterinary and human vaccines. Vaccine 19:2666–2672

    Article  CAS  PubMed  Google Scholar 

  • Badiee A, Khamesipour A, Samiei A, Soroush D, Shargh VH, Kheiri MT, Barkhordari F, Mc Master WR, Mahboudi F, Jaafari MR (2012) The role of liposome size on the type of immune response induced in BALB/c mice against leishmaniasis: rgp63 as a model antigen. Exp Parasitol 132:403–409

    Article  CAS  PubMed  Google Scholar 

  • Bastola R, Noh G, Keum T, Bashyal S, Seo JE, Choi J, Oh Y, Cho Y, Lee S (2017) Vaccine adjuvants: smart components to boost the immune system. Arch Pharmacal Res 40:1238–1248

    Article  CAS  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 

  • Burakova Y, Madera R, McVey S, Schlup JR, Shi J (2018) Adjuvants for animal vaccines. Viral Immunol 31:11–22

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Liu Y, Wang L, Liu Y, Zhang W, Fan B, Ma X, Yuan Q, Ma G, Su Z (2014) Enhanced humoral and cell-mediated immune responses generated by cationic polymer-coated PLA microspheres with adsorbed HBsAg. Mol Pharm 11:1772–1784

    Article  CAS  PubMed  Google Scholar 

  • Chithrani BD, Ghazani AA, Chan WCW (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668

    Article  CAS  PubMed  Google Scholar 

  • Foged C (2011) Subunit vaccines of the future: the need for safe, customized and optimized particulate delivery systems. Ther Deliv 2:1057–1077

    Article  CAS  PubMed  Google Scholar 

  • Freitas E, Marinho AC, Albuquerque D, Teles L, Sindeaux M, Salles MT, Sousa DC, Lima MM, da Guia Silva M, Fernandes D (2013) Adjuvant activity of peanut, cottonseed and rice oils on cellular and humoral response. VacciMonitor 22:4–9

    CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Henriksen-Lacey M, Devitt A, Perrie Y (2011) The vesicle size of DDA: TDB liposomal adjuvants plays a role in the cell-mediated immune response but has no significant effect on antibody production. J Control Release 154:131–137

    Article  CAS  PubMed  Google Scholar 

  • Iyer V, Cayatte C, Guzman B, Schneider-Ohrum K, Matuszak R, Snell A, Rajani GM, McCarthy MP, Muralidhara B (2015) Impact of formulation and particle size on stability and immunogenicity of oil-in-water emulsion adjuvants. Human Vaccines Immunother 11:1853–1864

    Article  Google Scholar 

  • Jansen T, Hofmans MPM, Theelen MJG, Manders F, Schijns VEJC (2006) Structure-and oil type-based efficacy of emulsion adjuvants. Vaccine 24:5400–5405

    Article  CAS  PubMed  Google Scholar 

  • Jin SE, Hwang SJ (2017) Ocular delivery systems for the administration of antibody therapeutics. J Pharm Investig 47:373–382

    Article  CAS  Google Scholar 

  • Liu Y, Yin Y, Wang L, Zhang W, Chen X, Yang X, Xu J, Ma G (2013) Surface hydrophobicity of microparticles modulates adjuvanticity. J Mater Chem B 1:3888–3896

    Article  CAS  PubMed  Google Scholar 

  • Mann JFS, Shakir E, Carter KC, Mullen AB, Alexander J, Ferro VA (2009) Lipid vesicle size of an oral influenza vaccine delivery vehicle influences the Th1/Th2 bias in the immune response and protection against infection. Vaccine 27:3643–3649

    Article  CAS  PubMed  Google Scholar 

  • Marasini N, Skwarczynski M, Toth I (2017) Intranasal delivery of nanoparticle-based vaccines. Ther Deliv 8:151–167

    Article  CAS  PubMed  Google Scholar 

  • Nakanishi T, Kunisawa J, Hayashi A, Tsutsumi Y, Kubo K, Nakagawa S, Nakanishi M, Tanaka K, Mayumi T (1999) Positively charged liposome functions as an efficient immunoadjuvant in inducing cell-mediated immune response to soluble proteins. J Control Release 61:233–240

    Article  CAS  PubMed  Google Scholar 

  • Oyewumi MO, Kumar A, Cui Z (2010) Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Expert Rev Vaccines 9:1095–1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park YM, Lee SJ, Kim YS, Lee MH, Cha GS, Jung ID, Kang TH, Han HD (2013) Nanoparticle-based vaccine delivery for cancer immunotherapy. Immune Netw 13:177–183

    Article  PubMed  PubMed Central  Google Scholar 

  • Schreiber HA, Prechl J, Jiang H, Zozulya A, Fabry Z, Denes F, Sandor M (2010) Using carbon magnetic nanoparticles to target, track, and manipulate dendritic cells. J Immunol Methods 356:47–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah RR, O’Hagan DT, Amiji MM, Brito LA (2014) The impact of size on particulate vaccine adjuvants. Nanomedicine 9:2671–2681

    Article  CAS  PubMed  Google Scholar 

  • Shah RR, Brito LA, O’Hagan DT, Amiji MM (2015a) Emulsions as vaccine adjuvants. In: Foged C, Rades T, Perrie Y, Hook S (eds) Subunit vaccine delivery. Springer, New York, pp 59–76

    Google Scholar 

  • Shah RR, Dodd S, Schaefer M, Ugozzoli M, Singh M, Otten GR, Amiji MM, O’Hagan DT, Brito LA (2015b) The development of self-emulsifying oil-in-water emulsion adjuvant and an evaluation of the impact of droplet size on performance. J Pharm Sci 104:1352–1361

    Article  CAS  PubMed  Google Scholar 

  • Sharma G, Valenta DT, Altman Y, Harvey S, Xie H, Mitragotri S, Smith JW (2010) Polymer particle shape independently influences binding and internalization by macrophages. J Control Release 147:408–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva AL, Rosalia RA, Varypataki E, Sibuea S, Ossendorp F, Jiskoot W (2015) Poly-(lactic-co-glycolic-acid)-based particulate vaccines: particle uptake by dendritic cells is a key parameter for immune activation. Vaccine 33:847–854

    Article  CAS  PubMed  Google Scholar 

  • Soema PC, Willems GJ, Jiskoot W, Amorij JP, Kersten GF (2015) Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach. Eur J Pharm Biopharm 94:427–435

    Article  CAS  PubMed  Google Scholar 

  • Tabata Y, Inoue Y, Ikada Y (1996) Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres. Vaccine 14:1677–1685

    Article  CAS  PubMed  Google Scholar 

  • Thiele L, Merkle HP, Walter E (2003) Phagocytosis and phagosomal fate of surface-modified microparticles in dendritic cells and macrophages. Pharm Res 20:221–228

    Article  CAS  PubMed  Google Scholar 

  • Thomas C, Rawat A, Hope-Weeks L, Ahsan F (2011) Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine responses to hepatitis B vaccine. Mol Pharm 8:405–415

    Article  CAS  PubMed  Google Scholar 

  • Vallhov H, Gabrielsson S, Strømme M, Scheynius A, Garcia-Bennett AE (2007) Mesoporous silica particles induce size dependent effects on human dendritic cells. Nano Lett 7:3576–3582

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Jiang H, Zhao Q, Wang S, Zou M, Cheng G (2012) Enhanced mucosal and systemic immune responses obtained by porous silica nanoparticles used as an oral vaccine adjuvant: effect of silica architecture on immunological properties. Int J Pharm 436:351–358

    Article  CAS  PubMed  Google Scholar 

  • Wilkhu JS, McNeil SE, Anderson DE, Perrie Y (2013) Characterization and optimization of bilosomes for oral vaccine delivery. J Drug Target 21:291–299

    Article  CAS  PubMed  Google Scholar 

  • Xiang SD, Scholzen A, Minigo G, David C, Apostolopoulos V, Mottram PL, Plebanski M (2006) Pathogen recognition and development of particulate vaccines: does size matter? Methods 40:1–9

    Article  CAS  PubMed  Google Scholar 

  • Yoo JW, Doshi N, Mitragotri S (2010) Endocytosis and intracellular distribution of PLGA particles in endothelial cells: effect of particle geometry. Macromol Rapid Commun 31:142–148

    Article  CAS  PubMed  Google Scholar 

  • Yotsumoto S, Aramaki Y, Kakiuchi T, Tsuchiya S (2004) Induction of antigen-dependent interleukin-12 production by negatively charged liposomes encapsulating antigens. Vaccine 22:3503–3509

    Article  CAS  PubMed  Google Scholar 

  • Zaman M, Good MF, Toth I (2013) Nanovaccines and their mode of action. Methods 60:226–231

    Article  CAS  PubMed  Google Scholar 

  • Zhao L, Seth A, Wibowo N, Zhao CX, Mitter N, Yu C, Middelberg APJ (2014) Nanoparticle vaccines. Vaccine 32:327–337

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by Technology Development Program (Project No. 316093-2 and Project No. 316094-2) for Bio-industry, Ministry for Agriculture, Food and Rural Affairs, Republic of Korea.

Author information

Authors and Affiliations

  1. College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Dalseo-Gu, Daegu, 42601, Republic of Korea

    Rakesh Bastola & Sangkil Lee

Authors
  1. Rakesh Bastola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sangkil Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sangkil Lee.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflicts of interest.

Research involving human participants and/or animals

This article does not contain any studies with human and animal subjects performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bastola, R., Lee, S. Physicochemical properties of particulate vaccine adjuvants: their pivotal role in modulating immune responses. J. Pharm. Investig. 49, 279–285 (2019). https://doi.org/10.1007/s40005-018-0406-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-018-0406-4

Keywords

Search

Navigation