Nanovaccines pp 61-103 | Cite as

PLGA-Based Mucosal Nanovaccines

  • Sergio Rosales-Mendoza
  • Omar González-Ortega


Poly(D,L-lactic-co-glycolic acid) (PLGA or PLG) is a linear copolymer composed of lactic and glycolic acids with biodegradability and biocompatibility properties recognized by the FDA. PLGA nanoparticles have been applied in vaccinology as antigen delivery vehicles capable of protecting antigens from degradation and being efficiently captured by antigen presenting cells. The current status on the development of PLGA-based nanovaccines is presented in this chapter and the key perspectives for this topic identified. Bacterial, viral, and allergic diseases have been targeted by using PLGA-based formulations. For most of the candidates enhanced humoral responses providing immunoprotection against experimental pathogen challenges has been achieved. Enhancement of cytotoxic lymphocyte responses has also been proven, generating relevant perspectives in the field of cancer immunotherapy. The promising findings from the evaluations of PLGA-based nanovaccines justifies the completion of preclinical evaluations for many candidates and, given the experience on the use of PLGA in the biomedical field, the beginning of clinical trials is anticipated in the short term. Therefore, among the currently available nanomaterials, PLGA nanoparticles are one of the most promising for the development of nanovaccines.


Poly(D,L-lactic-co-glycolic acid) Nanovaccine HIV/AIDS Hepatitis B Diphtheria Helicobacter pylori Enterotoxigenic E. coli 


  1. Adomako M, St-Hilaire S, Zheng Y, Eley J, Marcum RD, Sealey W, Donahower BC, Lapatra S, Sheridan PP (2012) Oral DNA vaccination of rainbow trout, Oncorhynchus mykiss (Walbaum), against infectious haematopoietic necrosis virus using PLGA [poly(D,L-lactic-co-glycolic acid)] nanoparticles. J Fish Dis 35(3):203–214CrossRefGoogle Scholar
  2. Barichello JM, Morishita M, Takayama K, Nagai T (1999) Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. Drug Dev Ind Pharm 25(4):471–476CrossRefGoogle Scholar
  3. Boyaka PN (2017) Inducing mucosal IgA: a challenge for vaccine adjuvants and delivery systems. J Immunol 199(1):9–16CrossRefGoogle Scholar
  4. Bussio JI, Molina-Perea C, González-Aramundiz JV (2018) Lower-sized chitosan Nanocapsules for transcutaneous antigen delivery. Nanomaterials (Basel) 26:8(9)Google Scholar
  5. Chen Q, Xu L, Liang C, Wang C, Peng R, Liu Z (2016) Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat Commun 7:13193CrossRefGoogle Scholar
  6. Chudina T, Labyntsev A, Manoilov K, Kolybo D, Komisarenko S (2015) Cellobiose-coated poly(lactide-co-glycolide) particles loaded with diphtheria toxoid for per os immunization. Croat Med J 56(2):85–93CrossRefGoogle Scholar
  7. Cohen-Sela E, Chorny M, Koroukhov N, Danenberg HD, Golomb G (2009) A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles. J Control Release 133(2):90–95CrossRefGoogle Scholar
  8. Conway MA, Madrigal-Estebas L, McClean S, Brayden DJ, Mills KH (2001) Protection against Bordetella pertussis infection following parenteral or oral immunization with antigens entrapped in biodegradable particles: effect of formulation and route of immunization on induction of Th1 and Th2 cells. Vaccine 19(15–16):1940–1950CrossRefGoogle Scholar
  9. Cruz LJ, Tacken PJ, Fokkink R, Joosten B, Stuart MC, Albericio F, Torensma R, Figdor CG (2010) Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro. J Control Release 144(2):118–126CrossRefGoogle Scholar
  10. Delgado A, Lavelle EC, Hartshorne M, Davis SS (1999) PLG microparticles stabilised using enteric coating polymers as oral vaccine delivery systems. Vaccine 17(22):2927–2938CrossRefGoogle Scholar
  11. Dubey S, Avadhani K, Mutalik S, Sivadasan SM, Maiti B, Paul J, Girisha SK, Venugopal MN, Mutoloki S, Evensen Ø, Karunasagar I, Munang’andu HM (2016) Aeromonas hydrophila OmpW PLGA nanoparticle Oral vaccine shows a dose-dependent protective immunity in Rohu (Labeo rohita). Vaccines (Basel) 4(2):pii: E21CrossRefGoogle Scholar
  12. Garinot M, Fiévez V, Pourcelle V, Stoffelbach F, des Rieux A, Plapied L, Theate I, Freichels H, Jérôme C, Marchand-Brynaert J, Schneider YJ, Préat V (2007) PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J Control Release 120(3):195–204CrossRefGoogle Scholar
  13. Ghotbi Z, Haddadi A, Hamdy S, Hung RW, Samuel J, Lavasanifar A (2011) Active targeting of dendritic cells with mannan-decorated PLGA nanoparticles. J Drug Target 19(4):281–292CrossRefGoogle Scholar
  14. Gornati L, Zanoni I, Granucci F (2018) Dendritic cells in the cross hair for the generation of tailored vaccines. Front Immunol 9:1484CrossRefGoogle Scholar
  15. Govender T, Stolnik S, Garnett MC, Illum L, Davis SS (1999) PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J Control Release 57(2):171–185CrossRefGoogle Scholar
  16. Gupta PN, Mahor S, Rawat A, Khatri K, Goyal A, Vyas SP (2006) Lectin anchored stabilized biodegradable nanoparticles for oral immunization 1. Development and in vitro evaluation. Int J Pharm 318(1–2):163–173CrossRefGoogle Scholar
  17. Gupta PN, Khatri K, Goyal AK, Mishra N, Vyas SP (2007) M-cell targeted biodegradable PLGA nanoparticles for oral immunization against hepatitis B. J Drug Target 15(10):701–713CrossRefGoogle Scholar
  18. Hayakawa Y, Godfrey DI, Smyth MJ (2004) α-Galactosylceramide: potential immunomodulatory activity and future application [general articles]. Curr Med Chem 11(2):241–252CrossRefGoogle Scholar
  19. Ho NI, Huis In’t Veld LGM, Raaijmakers TK, Adema GJ (2018) Adjuvants enhancing cross-presentation by dendritic cells: the key to more effective vaccines? Front Immunol 9:2874CrossRefGoogle Scholar
  20. Iranpour S, Nejati V, Delirezh N, Biparva P, Shirian S (2016) Enhanced stimulation of anti-breast cancer T cells responses by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated tumor antigens. J Exp Clin Cancer Res 35(1):168CrossRefGoogle Scholar
  21. Jahan ST, Sadat SM, Haddadi A (2018) Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine. Int J Nanomedicine 13:367–386CrossRefGoogle Scholar
  22. Jung T, Kamm W, Breitenbach A, Hungerer KD, Hundt E, Kissel T (2001) Tetanus toxoid loaded nanoparticles from sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide): evaluation of antibody response after oral and nasal application in mice. Pharm Res 18(3):352–360CrossRefGoogle Scholar
  23. Kaneko K, McDowell A, Ishii Y, Hook S (2017) Characterization and evaluation of stabilized particulate formulations as therapeutic oral vaccines for allergy. J Liposome Res 21:1–28Google Scholar
  24. Kim SY, Doh HJ, Ahn JS, Ha YJ, Jang MH, Chung SI, Park HJ (1999a) Induction of mucosal and systemic immune response by oral immunization with H. pylori lysates encapsulated in poly(D,L-lactide-co-glycolide) microparticles. Vaccine 17(6):607–616CrossRefGoogle Scholar
  25. Kim SY, Doh HJ, Jang MH, Ha YJ, Chung SI, Park HJ (1999b) Oral immunization with helicobacter pylori-loaded poly(D, L-lactide-co-glycolide) nanoparticles. Helicobacter 4(1):33–39CrossRefGoogle Scholar
  26. Kim H, Griffith T, Panyam J (2019) Poly(D,L-lactide-co-glycolide) nanoparticles as a vaccine delivery platform for TLR7/8 agonist-based cancer vaccine. J Pharmacol Exp Ther 370(3):715–724. Scholar
  27. Lactel (2019) Absorbable polymers. Visited on 2019
  28. Lee PW, Pokorski JK (2018) Poly(lactic-co-glycolic acid) devices: production and applications for sustained protein delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol. Scholar
  29. Liu W, Wen S, Shen M, Shi X (2014) Doxorubicin-loaded poly (lactic-co-glycolic acid) hollow microcapsules for targeted drug delivery to cancer cells. New J Chem 38(8):3917–3924CrossRefGoogle Scholar
  30. Ma T, Wang L, Yang T, Ma G, Wang S (2014) M-cell targeted polymeric lipid nanoparticles containing a toll-like receptor agonist to boost oral immunity. Int J Pharm 473(1–2):296–303CrossRefGoogle Scholar
  31. Ma YP, Ke H, Liang ZL, Ma JY, Hao L, Liu ZX (2017) Protective efficacy of cationic-PLGA microspheres loaded with DNA vaccine encoding the sip gene of Streptococcus agalactiae in tilapia. Fish Shellfish Immunol 66:345–353CrossRefGoogle Scholar
  32. McConnell EL, Basit AW, Murdan S (2008) Colonic antigen administration induces significantly higher humoral levels of colonic and vaginal IgA, and serum IgG compared to oral administration. Vaccine 26(5):639–646CrossRefGoogle Scholar
  33. Mishra N, Tiwari S, Vaidya B, Agrawal GP, Vyas SP (2011) Lectin anchored PLGA nanoparticles for oral mucosal immunization against hepatitis B. J Drug Target 19(1):67–78CrossRefGoogle Scholar
  34. Nazarian S, Gargari SL, Rasooli I, Hasannia S, Pirooznia N (2014) A PLGA-encapsulated chimeric protein protects against adherence and toxicity of enterotoxigenic Escherichia coli. Microbiol Res 169(2–3):205–212CrossRefGoogle Scholar
  35. Niborski V, Li Y, Brennan F, Lane M, Torché AM, Remond M, Bonneau M, Riffault S, Stirling C, Hutchings G, Takamatsu H, Barnett P, Charley B, Schwartz-Cornil I (2006) Efficacy of particle-based DNA delivery for vaccination of sheep against FMDV. Vaccine 24(49–50):7204–7213CrossRefGoogle Scholar
  36. Pan L, Zhang Z, Lv J, Zhou P, Hu W, Fang Y, Chen H, Liu X, Shao J, Zhao F, Ding Y, Lin T, Chang H, Zhang J, Zhang Y, Wang Y (2014) Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles. Int J Nanomedicine 9:5603–5618CrossRefGoogle Scholar
  37. Sarti F, Perera G, Hintzen F, Kotti K, Karageorgiou V, Kammona O, Kiparissides C, Bernkop-Schnürch A (2011) In vivo evidence of oral vaccination with PLGA nanoparticles containing the immunostimulant monophosphoryl lipid A. Biomaterials 32(16):4052–4057CrossRefGoogle Scholar
  38. Silva AL, Soema PC, Slütter B, Ossendorp F, Jiskoot W (2016) PLGA particulate delivery systems for subunit vaccines: linking particle properties to immunogenicity. Hum Vaccin Immunother 12(4):1056–1069CrossRefGoogle Scholar
  39. Tan Z, Liu W, Liu H, Li C, Zhang Y, Meng X, Tang T, Xi T, Xing Y (2017) Oral helicobacter pylori vaccine-encapsulated acid-resistant HP55/PLGA nanoparticles promote immune protection. Eur J Pharm Biopharm 111:33–43CrossRefGoogle Scholar
  40. Wang G, Pan L, Zhang Y, Wang Y, Zhang Z, Lü J, Zhou P, Fang Y, Jiang S (2011) Intranasal delivery of cationic PLGA nano/microparticles-loaded FMDV DNA vaccine encoding IL-6 elicited protective immunity against FMDV challenge. PLoS One 6(11):e27605CrossRefGoogle Scholar
  41. Wang Y, Wen Q, Choi S (2016a) FDA’s regulatory science program for generic PLA/PLGA-based drug products. Am Pharm Rev 19(4):5–9Google Scholar
  42. Wang Y, Li P, Truong-Dinh Tran T, Zhang J, Kong L (2016b) Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer. Nanomaterials 6(2):26CrossRefGoogle Scholar
  43. WHO (2013) Global vaccine action plan 2011–2020. World Health OrganizationGoogle Scholar
  44. Xu Y, Kim CS, Saylor DM, Koo D (2017) Polymer degradation and drug delivery in PLGA-based drug-polymer applications: a review of experiments and theories. J Biomed Mater Res B Appl Biomater 105(6):1692–1716CrossRefGoogle Scholar
  45. Yang X, Lian K, Meng T, Liu X, Miao J, Tan Y, Yuan H, Hu F (2018) Immune adjuvant targeting micelles allow efficient dendritic cell migration to lymph nodes for enhanced cellular immunity. ACS Appl Mater Interfaces 10(39):33532–33544. Scholar
  46. Zhang L, Zeng Z, Hu C, Bellis SL, Yang W, Su Y, Zhang X, Wu Y (2016) Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines. Biomaterials 77:307–319CrossRefGoogle Scholar
  47. Zhu Q, Talton J, Zhang G, Cunningham T, Wang Z, Waters RC, Kirk J, Eppler B, Klinman DM, Sui Y, Gagnon S, Belyakov IM, Mumper RJ, Berzofsky JA (2012) Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection. Nat Med 18(8):1291–1296CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sergio Rosales-Mendoza
    • 1
  • Omar González-Ortega
    • 2
  1. 1.Facultad de Ciencias Químicas, Centro de Investigación en Ciencias de la Salud y BiomedicinaUniversidad Autónoma de San Luis PotosíSan Luis PotosíMexico
  2. 2.Facultad de Ciencias QuímicasUniversidad Autónoma de San Luis Potosí San Luis PotosíMexico

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