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Review

Demystifying particle-based oral vaccines

&
Pages 1455-1472 | Received 25 Apr 2021, Accepted 18 Jun 2021, Published online: 06 Jul 2021

References

  • Shakya AK, Chowdhury MYE, Tao W, et al. Mucosal vaccine delivery: current state and a pediatric perspective. J Control Release. 2016 Oct 28;240:394–413.
  • Li M, Wang Y, Sun Y, et al. Mucosal vaccines: strategies and challenges. Immunol Lett. 2020;217:116–125.
  • Holmgren J, Czerkinsky C. Mucosal immunity and vaccines. Nat Med. 2005 Apr;11(4 Suppl):S45–53.
  • Iwasaki A. Exploiting mucosal immunity for antiviral vaccines. Annu Rev Immunol. 2016;34(1):575–608.
  • Sulczewski FB, Liszbinski RB, PRT R, et al. Nanoparticle vaccines against viral infections. Arch Virol. 2018;163(9):2313–2325.
  • World Health O. Polio vaccines: WHO position paper. Wkly Epidemiol Rec. 2014;89(9):73–92.
  • Pokharkar V, Bhumkar D, Suresh K, et al. Gold nanoparticles as a potential carrier for transmucosal vaccine delivery. J Biomed Nanotechnol. 2011 Feb;7(1):57–59.
  • Dewangan HK, Pandey T, Maurya L, et al. Rational design and evaluation of HBsAg polymeric nanoparticles as antigen delivery carriers. Int J Biol Macromol. 2018 May;111:804–812.
  • Khanifar J, Hosseini RH, Kazemi R, et al. Prevention of EHEC infection by chitosan nano-structure coupled with synthetic recombinant antigen. J Microbiol Methods. 2019 Feb;157:100–107.
  • Atwe SU, Ma Y, Gill HS. Pollen grains for oral vaccination. J Control Release. 2014Nov 28;194(194):45–52.
  • Uddin MJ, Gill HS. From allergen to oral vaccine carrier: a new face of ragweed pollen. Int J Pharm. 2018 Jul 10; 545(1–2):286–294.
  • Storni T, Kündig TM, Senti G, et al. Immunity in response to particulate antigen-delivery systems. Adv Drug Deliv Rev. 2005 Jan 10;57(3):333–355.
  • Rice-Ficht AC, Arenas-Gamboa AM, Kahl-McDonagh MM, et al. Polymeric particles in vaccine delivery. Curr Opin Microbiol. 2010 Feb 01;13(1):106–112.
  • Westwood A, Healey GD, Williamson ED, et al. Activation of dendritic cells by microparticles containing Bacillus anthracis protective antigen. Vaccine. 2005 May 31;23(29):3857–3863.
  • Johansen P, Storni T, Rettig L, et al. Antigen kinetics determines immune reactivity. PNAS. 2008;105(13):5189–5194. 03/24 07/05/received.
  • Sharp FA, Ruane D, Claass B, et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome [10.1073/pnas.0804897106]. PNAS. 2009;106(3):870.
  • Sasaki S, Okuda K. The Use of Conventional Immunologic Adjuvants in DNA Vaccine Preparations. In: Lowrie DB, Whalen RG, editors. DNA Vaccines: methods and Protocols. Totowa, NJ: Humana Press; 2000. p. 241–249.
  • Xiang SD, Scholzen A, Minigo G, et al. Pathogen recognition and development of particulate vaccines: does size matter? Methods. 2006 Sep 01;40(1):1–9.
  • Mörbe UM, Jørgensen PB, Fenton TM, et al. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal Immunol. 2021 March 22; https://doi.org/10.1038/s41385-021-00389-4.
  • O’Hagan DT, Palin KJ, Davis SS. Poly(butyl-2-cyanoacrylate) particles as adjuvants for oral immunization. Vaccine. 1989 Jun;7(3):213–216.
  • O’Hagan DT, Palin K, Davis SS, et al. Microparticles as potentially orally active immunological adjuvants. Vaccine. 1989 Oct;7(5):421–424.
  • Uchida T, Goto S. Oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin as vaccine formulation: particle size study. Biol Pharm Bull. 1994 Sep;17(9):1272–1276.
  • Heritage PL, Underdown BJ, Brook MA, et al. Oral administration of polymer-grafted starch microparticles activates gut-associated lymphocytes and primes mice for a subsequent systemic antigen challenge. Vaccine. 1998 Dec;16(20):2010–2017.
  • Prokop A, Kozlov E, Newman GW, et al. Water-based nanoparticulate polymeric system for protein delivery: permeability control and vaccine application. Biotechnol Bioeng. 2002 May 20;78(4):459–466.
  • Gomez S, Gamazo C, Roman BS, et al. Gantrez AN nanoparticles as an adjuvant for oral immunotherapy with allergens. Vaccine. 2007 Jul 20;25(29):5263–5271.
  • Garinot M, Fievez V, Pourcelle V, et al. PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. J Control Release. 2007 Jul 31;120(3):195–204.
  • Chen F, Zhang ZR, Yuan F, et al. In vitro and in vivo study of N-trimethyl chitosan nanoparticles for oral protein delivery. Int J Pharm. 2008 Feb 12;349(1–2):226–233.
  • Salman HH, Gamazo C, Agueros M, et al. Bioadhesive capacity and immunoadjuvant properties of thiamine-coated nanoparticles. Vaccine. 2007 Nov 23;25(48):8123–8132.
  • Berner VK, Sura ME, Hunter KW Jr. Conjugation of protein antigen to microparticulate beta-glucan from Saccharomyces cerevisiae: a new adjuvant for intradermal and oral immunizations. Appl Microbiol Biotechnol. 2008 Oct;80(6):1053–1061.
  • Kuo-Haller P, Cu Y, Blum J, et al. Vaccine delivery by polymeric vehicles in the mouse reproductive tract induces sustained local and systemic immunity. Mol Pharm. 2010 Oct 4;7(5):1585–1595.
  • Carvalho LV, Ruiz Rde C, Scaramuzzi K, et al. Immunological parameters related to the adjuvant effect of the ordered mesoporous silica SBA-15. Vaccine. 2010 Nov 23;28(50):7829–7836.
  • Malik B, Goyal AK, Markandeywar TS, et al. Microfold-cell targeted surface engineered polymeric nanoparticles for oral immunization. J Drug Target. 2012 Jan;20(1):76–84.
  • Wang T, Jiang H, Zhao Q, et al. 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. 2012 Oct 15;436(1–2):351–358.
  • Goldmann K, Ensminger SM, Spriewald BM. Oral gene application using chitosan-DNA nanoparticles induces transferable tolerance. Clin Vaccine Immunol. 2012 Nov;19(11):1758–1764.
  • Suksamran T, Ngawhirunpat T, Rojanarata T, et al. Methylated N-(4-N,N-dimethylaminocinnamyl) chitosan-coated electrospray OVA-loaded microparticles for oral vaccination. Int J Pharm. 2013 May 1;448(1):19–27.
  • De Smet R, Demoor T, Verschuere S, et al. beta-Glucan microparticles are good candidates for mucosal antigen delivery in oral vaccination. J Control Release. 2013 Dec 28;172(3):671–678.
  • Harde H, Agrawal AK, Jain S. Development of stabilized glucomannosylated chitosan nanoparticles using tandem crosslinking method for oral vaccine delivery. Nanomedicine (Lond). 2014 Nov;9(16):2511–2529.
  • Xu B, Zhang W, Chen Y, et al. Eudragit(R) L100-coated mannosylated chitosan nanoparticles for oral protein vaccine delivery. Int J Biol Macromol. 2018 Jul 1;113:534–542.
  • von Halling Laier C, Gibson B, van de Weert M, et al. Spray dried cubosomes with ovalbumin and Quil-A as a nanoparticulate dry powder vaccine formulation. Int J Pharm. 2018 Oct 25;550(1–2):35–44.
  • von Halling Laier C, Gibson B, Moreno JAS, et al. Microcontainers for protection of oral vaccines, in vitro and in vivo evaluation. J Control Release. 2019 Jan 28;294:91–101.
  • Snook JD, Chesson CB, Peniche AG, et al. Peptide nanofiber-CaCO3 composite microparticles as adjuvant-free oral vaccine delivery vehicles. J Mater Chem B. 2016 Mar 7; 4(9):1640–1649.
  • Rajkannan R, Dhanaraju MD, Gopinath D, et al. Development of hepatitis B oral vaccine using B-cell epitope loaded PLG microparticles. Vaccine. 2006 Jun 12; 24(24):5149–5157.
  • Jain AK, Goyal AK, Mishra N, et al. PEG-PLA-PEG block copolymeric nanoparticles for oral immunization against hepatitis B. Int J Pharm. 2010 Mar 15; 387(1–2):253–262.
  • Mishra N, Tiwari S, Vaidya B, et al. Lectin anchored PLGA nanoparticles for oral mucosal immunization against hepatitis B. J Drug Target. 2011 Jan;19(1):67–78.
  • Mishra N, Khatri K, Gupta M, et al. Development and characterization of LTA-appended chitosan nanoparticles for mucosal immunization against hepatitis B. Artif Cells Nanomed Biotechnol. 2014 Aug;42(4):245–255.
  • Shrestha B, Rath JP. Poly(vinyl alcohol)-coated chitosan microparticles act as an effective oral vaccine delivery system for hepatitis B vaccine in rat model. IET Nanobiotechnol. 2014 Dec;8(4):201–207.
  • Scaramuzzi K, Oliveira DC, Carvalho LV, et al. Nanostructured SBA-15 silica as an adjuvant in immunizations with hepatitis B vaccine. Einstein (Sao Paulo). 2011 Dec; 9(4):436–441.
  • Chen XY, Butt AM, Mohd Amin MCI. Molecular Evaluation of Oral Immunogenicity of Hepatitis B Antigen Delivered by Hydrogel Microparticles. Mol Pharm. 2019 Sep 3; 16(9):3853–3872.
  • Saraf S, Jain S, Sahoo RN, et al. Lipopolysaccharide derived alginate coated Hepatitis B antigen loaded chitosan nanoparticles for oral mucosal immunization. Int J Biol Macromol. 2020 Jul 1;154:466–476.
  • Karimi Bavandpour A, Bakhshi B, Najar-Peerayeh S. The roles of mesoporous silica and carbon nanoparticles in antigen stability and intensity of immune response against recombinant subunit B of cholera toxin in a rabbit animal model. Int J Pharm. 2020 Jan 5;573:118868.
  • Ghaffari Marandi BH, Zolfaghari MR, Kazemi R, et al. Immunization against Vibrio cholerae, ETEC, and EHEC with chitosan nanoparticle containing LSC chimeric protein. Microb Pathog. 2019 Sep;134:103600.
  • Pastor M, Esquisabel A, Marquinez I, et al. Cellulose acetate phthalate microparticles containing Vibrio cholerae: steps toward an oral cholera vaccine. J Drug Target. 2014 Jul;22(6):478–487.
  • Pastor M, Esquisabel A, Talavera A, et al. An approach to a cold chain free oral cholera vaccine: in vitro and in vivo characterization of Vibrio cholerae gastro-resistant microparticles. Int J Pharm. 2013 [2013 May 1];448(1):247–258.
  • Stertman L, Lundgren E, Sjoholm I. Starch microparticles as a vaccine adjuvant: only uptake in Peyer’s patches decides the profile of the immune response. Vaccine. 2006Apr 24; 24(17):3661–3668.
  • Yeh M, Chiang C. Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles: in vitro release and oral vaccination. J Microencapsul. 2004 Feb;21(1):91–106.
  • Yeh MK, Liu YT, Chen JL, et al. Oral immunogenicity of the inactivated Vibrio cholerae whole-cell vaccine encapsulated in biodegradable microparticles. J Control Release. 2002 Aug 21;82(2–3)237–247.
  • Ushijima H, Machida S, Nomura A, et al. Immune responses against norovirus GII.4 virus-like particles in mice. Acta Virol. 2016;60(4):339–346.
  • Zhang X, Buehner NA, Hutson AM, et al. Tomato is a highly effective vehicle for expression and oral immunization with Norwalk virus capsid protein. Plant Biotechnol J. 2006 Jul;4(4):419–432.
  • Huang Z, Elkin G, Maloney BJ, et al. Virus-like particle expression and assembly in plants: hepatitis B and Norwalk viruses. Vaccine. 2005Mar 7; 23(15):1851–1858.
  • Nicollier-Jamot B, Ogier A, Piroth L, et al. Recombinant virus-like particles of a norovirus (genogroup II strain) administered intranasally and orally with mucosal adjuvants LT and LT(R192G) in BALB/c mice induce specific humoral and cellular Th1/Th2-like immune responses. Vaccine. 2004 Mar 12; 22(9–10):1079–1086.
  • Tacket CO, Sztein MB, Losonsky GA, et al. Humoral, mucosal, and cellular immune responses to oral Norwalk virus-like particles in volunteers. Clin Immunol. 2003 Sep;108(3):241–247.
  • Periwal SB, Kourie KR, Ramachandaran N, et al. A modified cholera holotoxin CT-E29H enhances systemic and mucosal immune responses to recombinant Norwalk virus-virus like particle vaccine. Vaccine. 2003 Jan 17;21(5–6):376–385.
  • Tacket CO, Mason HS, Losonsky G, et al. Human immune responses to a novel norwalk virus vaccine delivered in transgenic potatoes. J Infect Dis. 2000 Jul;182(1):302–305.
  • Mason HS, Ball JM, Shi JJ, et al. Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc Natl Acad Sci U S A. 1996 May 28; 93(11):5335–5340.
  • van der Lubben IM, Kersten G, Fretz MM, et al. Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine. 2003 Mar 28; 21(13–14):1400–1408.
  • Rydell N, Sjoholm I. Oral vaccination against diphtheria using polyacryl starch microparticles as adjuvant. Vaccine. 2004 Mar 12; 22(9–10):1265–1274.
  • Rydell N, Sjoholm I. Mucosal vaccination against diphtheria using starch microparticles as adjuvant for cross-reacting material (CRM197) of diphtheria toxin. Vaccine. 2005 Apr 15; 23(21):2775–2783.
  • Rydell N, Stertman L, Stalenheim G, et al. Use of an oral diphtheria vaccine in human. Vaccine. 2006 Aug 14; 24(33–34):5928–5930.
  • Chudina T, Labyntsev A, Manoilov K, et al. Cellobiose-coated poly(lactide-co-glycolide) particles loaded with diphtheria toxoid for per os immunization. Croat Med J. 2015 Apr;56(2):85–93.
  • Harde H, Siddhapura K, Agrawal AK, et al. Divalent toxoids loaded stable chitosan-glucomannan nanoassemblies for efficient systemic, mucosal and cellular immunostimulatory response following oral administration. Int J Pharm. 2015 Jun 20; 487(1–2):292–304.
  • Shukla A, Mishra V, Bhoop BS, et al. Alginate coated chitosan microparticles mediated oral delivery of diphtheria toxoid Part A. Systematic optimization, development and characterization. Int J Pharm. 2015 Nov 10; 495(1):220–233.
  • Vandamme K, Melkebeek V, Cox E, et al. Adjuvant effect of Gantrez(R)AN nanoparticles during oral vaccination of piglets against F4+enterotoxigenic Escherichia coli. Vet Immunol Immunopathol. 2011 Feb 15; 139(2–4):148–155.
  • Vandamme K, Melkebeek V, Cox E, et al. Influence of polymer hydrolysis on adjuvant effect of Gantrez(R)AN nanoparticles: implications for oral vaccination. Eur J Pharm Biopharm. 2011 Oct;79(2):392–398.
  • Hosseini ZS, Amani J, Baghbani Arani F, et al. Immunogenicity of the nanovaccine containing intimin recombinant protein in the BALB/c mice. Clin Exp Vaccine Res. 2018 Jan;7(1):51–60.
  • Noroozi N, Gargari SLM, Nazarian S, et al. Immunogenicity of enterotoxigenic Escherichia coli outer membrane vesicles encapsulated in chitosan nanoparticles. Iran J Basic Med Sci. 2018 Mar;21(3):284–291.
  • Hajizade A, Salmanian AH, Amani J, et al. EspA-loaded mesoporous silica nanoparticles can efficiently protect animal model against enterohaemorrhagic E. coli O157: H7. Artif Cells Nanomed Biotechnol. 2018;46(sup3):S1067–S1075.
  • Almasian P, Amani J, Arani FB, et al. Preparation of chitosan nanoparticle containing recombinant StxB antigen of EHEC and evaluation its immunogenicity in BALB/c mice. Iran J Microbiol. 2018 Dec;10(6):361–370.
  • Global, regional, and national age&#x. 2013;sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385(9963):117–171.
  • Chen SC, Jones DH, Fynan EF, et al. Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles. J Virol. 1998 Jul;72(7):5757–5761.
  • Herrmann JE, Chen SC, Jones DH, et al. Immune responses and protection obtained by oral immunization with rotavirus VP4 and VP7 DNA vaccines encapsulated in microparticles. Virology. 1999 Jun 20; 259(1):148–153.
  • Kim SY, Doh HJ, Ahn JS, et al. Induction of mucosal and systemic immune response by oral immunization with Hpylori lysates encapsulated in poly(D,L-lactide-co-glycolide) microparticles. Vaccine. 1999 Feb 12; 17(6):607–616.
  • Kim SY, Doh HJ, Jang MH, et al. Oral immunization with Helicobacter pylori-loaded poly(D, L-lactide-co-glycolide) nanoparticles. Helicobacter. 1999 Mar;4(1):33–39.
  • Rose RC, Lane C, Wilson S, et al. Oral vaccination of mice with human papillomavirus virus-like particles induces systemic virus-neutralizing antibodies. Vaccine. 1999 Apr 23; 17(17):2129–2135.
  • Li T, Takeda N, Miyamura T. Oral administration of hepatitis E virus-like particles induces a systemic and mucosal immune response in mice. Vaccine. 2001 May 14; 19(25–26):3476–3484.
  • Rebelatto MC, Guimond P, Bowersock TL, et al. Induction of systemic and mucosal immune response in cattle by intranasal administration of pig serum albumin in alginate microparticles. Vet Immunol Immunopathol. 2001 Nov;83(1–2):93–105.
  • Carcaboso AM, Hernandez RM, Igartua M, et al. Immune response after oral administration of the encapsulated malaria synthetic peptide SPf66. Int J Pharm. 2003 Jul 24; 260(2):273–282.
  • Chew JL, Wolfowicz CB, Mao HQ, et al. Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice. Vaccine. 2003 Jun 20; 21(21–22):2720–2729.
  • Takamura S, Niikura M, Li TC, et al. DNA vaccine-encapsulated virus-like particles derived from an orally transmissible virus stimulate mucosal and systemic immune responses by oral administration. Gene Ther. 2004 Apr;11(7):628–635.
  • Zhang H, Huang Y, Fayad R, et al. Induction of mucosal and systemic neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) by oral immunization with bovine Papillomavirus-HIV-1 gp41 chimeric virus-like particles. J Virol. 2004 Aug; 78(15):8342–8348.
  • Roth-Walter F, Scholl I, Untersmayr E, et al. Mucosal targeting of allergen-loaded microspheres by Aleuria aurantia lectin. Vaccine. 2005 Apr 15; 23(21):2703–2710.
  • Li GP, Liu ZG, Liao B, et al. Induction of Th1-type immune response by chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen Der p 2 for oral vaccination in mice. Cell Mol Immunol. 2009 Feb; 6(1):45–50.
  • Zhang GG, Li DX, Zhang HH, et al. Enhancement of mucosal immune response against the M2eHBc+ antigen in mice with the fusion expression products of LTB and M2eHBc+ through mucosal immunization route. Vet Res Commun. 2009 Oct; 33(7):735–747.
  • Camacho AI, de Souza J, Sanchez-Gomez S, et al. Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice. Vaccine. 2011 Oct 26; 29(46):8222–8229.
  • Nayak B, Ray AR, Panda AK, et al. Improved immunogenicity of biodegradable polymer particles entrapped rotavirus vaccine. J Biomater Appl. 2011 Jan;25(5):469–496.
  • Chablani L, Tawde SA, Akalkotkar A, et al. Formulation and evaluation of a particulate oral breast cancer vaccine. J Pharm Sci. 2012 Oct;101(10):3661–3671.
  • Shastri PN, Kim MC, Quan FS, et al. Immunogenicity and protection of oral influenza vaccines formulated into microparticles. J Pharm Sci. 2012 Oct;101(10):3623–3635.
  • Zhai Y, Zhong Z, Zariffard M, et al. Bovine papillomavirus-like particles presenting conserved epitopes from membrane-proximal external region of HIV-1 gp41 induced mucosal and systemic antibodies. Vaccine. 2013 Nov 4; 31(46)5422–5429.
  • Guillen D, Moreno-Mendieta S, Perez R, et al. Starch granules as a vehicle for the oral administration of immobilized antigens. Carbohydr Polym. 2014 Nov 4;112(112):210–215.
  • Jiang T, Singh B, Li HS, et al. Targeted oral delivery of BmpB vaccine using porous PLGA microparticles coated with M cell homing peptide-coupled chitosan. Biomaterials. 2014 Feb;35(7):2365–2373.
  • Moreno-Mendieta SA, Guillen D, Espitia C, et al. A novel antigen-carrier system: the mycobacterium tuberculosis acr protein carried by raw starch microparticles. Int J Pharm. 2014 Oct 20; 474(1–2):241–248.
  • Abkar M, Lotfi AS, Amani J, et al. Survey of Omp19 immunogenicity against Brucella abortus and Brucella melitensis: influence of nanoparticulation versus traditional immunization. Vet Res Commun. 2015 Dec; 39(4):217–228.
  • Biswas S, Chattopadhyay M, Sen KK, et al. Development and characterization of alginate coated low molecular weight chitosan nanoparticles as new carriers for oral vaccine delivery in mice. Carbohydr Polym. 2015 May 5;121(121):403–410.
  • Harde H, Agrawal AK, Jain S. Tetanus toxoids loaded glucomannosylated chitosan based nanohoming vaccine adjuvant with improved oral stability and immunostimulatory response. Pharm Res. 2015 Jan;32(1):122–134.
  • Singh B, Maharjan S, Jiang T, et al. Combinatorial approach of antigen delivery using M cell-homing peptide and mucoadhesive vehicle to enhance the efficacy of oral vaccine. Mol Pharm. 2015 Nov 2; 12(11):3816–3828.
  • Tan Z, Liu W, Liu H, et al. Oral Helicobacter pylori vaccine-encapsulated acid-resistant HP55/PLGA nanoparticles promote immune protection. Eur J Pharm Biopharm. 2017 Feb;111:33–43.
  • Costa MM, Esteves C, Castedo JL, et al. A challenging coexistence of central diabetes insipidus and cerebral salt wasting syndrome: a case report. J Med Case Rep. 2018 Jul 17; 12(1):212.
  • Ren Z, Zhao Y, Liu J, et al. Inclusion of membrane-anchored LTB or flagellin protein in H5N1 virus-like particles enhances protective responses following intramuscular and oral immunization of mice. Vaccine. 2018 Sep 25; 36(40)5990–5998.
  • Tabrizi NM, Amani J, Ebrahimzadeh M, et al. Preparation and evaluation of chitosan nanoparticles containing CtxB antigen against Vibrio cholera. Microb Pathog. 2018 Nov;124:170–177.
  • Qi X, Lu Q, Hu J, et al. Spontaneous C-cleavage of a truncated intein as fusion tag to produce tag-free VP1 inclusion body nanoparticle vaccine against CVB3-induced viral myocarditis by the oral route. Microb Cell Fact. 2019 Apr 4; 18(1):66.
  • Marasini N, Giddam AK, Ghaffar KA, et al. Multilayer engineered nanoliposomes as a novel tool for oral delivery of lipopeptide-based vaccines against group A Streptococcus. Nanomedicine (Lond). 2016 May;11(10):1223–1236.
  • Bartlett S, Eichenberger RM, Nevagi RJ, et al. Lipopeptide-based oral vaccine against hookworm infection. J Infect Dis. 2020 Mar 2; 221(6):934–942.
  • Lai YH, D’Souza MJ. Formulation and evaluation of an oral melanoma vaccine. J Microencapsul. 2007 May;24(3):235–252.
  • Lee DY, Nurunnabi M, Kang SH, et al. Oral Gavage Delivery of PR8 Antigen with beta-Glucan-Conjugated GRGDS Carrier to Enhance M-Cell Targeting Ability and Induce Immunity. Biomacromolecules. 2017 Apr 10; 18(4):1172–1179.
  • Mao R, Chen Y, Wu Q, et al. Oral delivery of single-chain insulin (SCI-59) analog by bacterium-like particles (BLPs) induces oral tolerance and prevents autoimmune diabetes in NOD mice. Immunol Lett. 2019 Oct;214:37–44.
  • Yeboah KG, D’Souza MJ. Evaluation of albumin microspheres as oral delivery system for Mycobacterium tuberculosis vaccines. J Microencapsul. 2009 Mar;26(2):166–179.
  • Jones DH, Corris S, McDonald S, et al. Poly(DL-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and mucosal antibody responses to encoded protein after oral administration. Vaccine. 1997 Jun;15(8):814–817.
  • Jones DH, Clegg JC, Farrar GH. Oral delivery of micro-encapsulated DNA vaccines. Dev Biol Stand. 1998;92:149–155.
  • Roy K, Mao HQ, Huang SK, et al. Oral gene delivery with chitosan--DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med. 1999 Apr;5(4):387–391.
  • Guetard D, Greco R, Cervantes Gonzalez M, et al. Immunogenicity and tolerance following HIV-1/HBV plant-based oral vaccine administration. Vaccine. 2008 Aug 18; 26(35):4477–4485.
  • Manrique M, Kozlowski PA, Cobo-Molinos A, et al. Immunogenicity of a vaccine regimen composed of simian immunodeficiency virus DNA, rMVA, and viral particles administered to female rhesus macaques via four different mucosal routes. J Virol. 2013 Apr;87(8):4738–4750.
  • Bivas-Benita M, Laloup M, Versteyhe S, et al. Generation of Toxoplasma gondii GRA1 protein and DNA vaccine loaded chitosan particles: preparation, characterization, and preliminary in vivo studies. Int J Pharm. 2003 Nov 6; 266(1–2):17–27.
  • Maloy KJ, Donachie AM, O’Hagan DT, et al. Induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in poly(lactide-co-glycolide) microparticles. Immunology. 1994 Apr;81(4):661–667.
  • Challacombe SJ, Rahman D, O’Hagan DT. Salivary, gut, vaginal and nasal antibody responses after oral immunization with biodegradable microparticles. Vaccine. 1997 Feb;15(2):169–175.
  • Delgado A, Lavelle EC, Hartshorne M, et al. PLG microparticles stabilised using enteric coating polymers as oral vaccine delivery systems. Vaccine. 1999 Jul 16; 17(22):2927–2938.
  • Wikingsson L, Sjoholm I. Polyacryl starch microparticles as adjuvant in oral immunisation, inducing mucosal and systemic immune responses in mice. Vaccine. 2002 Sep 10; 20(27–28):3355–3363.
  • Gutierro I, Hernandez RM, Igartua M, et al. Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine. 2002 Nov 22; 21(1–2):67–77.
  • Stertman L, Strindelius L, Sjoholm I. Starch microparticles as an adjuvant in immunisation: effect of route of administration on the immune response in mice. Vaccine. 2004 Jul 29; 22(21–22):2863–2872.
  • Jain S, Sharma RK, Vyas SP. Chitosan nanoparticles encapsulated vesicular systems for oral immunization: preparation, in-vitro and in-vivo characterization. J Pharm Pharmacol. 2006 Mar;58(3):303–310.
  • Hurtado-Lopez P, Murdan S. An investigation into the adjuvanticity and immunogenicity of zein microspheres being researched as drug and vaccine carriers. J Pharm Pharmacol. 2006 Jun;58(6):769–774.
  • Ahire VJ, Sawant KK, Doshi JB, et al. Chitosan microparticles as oral delivery system for tetanus toxoid. Drug Dev Ind Pharm. 2007 Oct;33(10):1112–1124.
  • Holmdahl L. A misleading meta-analysis of seprafilm. World J Surg. 2008 Aug;32(8):1888–1889. author reply 1890–1.
  • Heritage PL, Loomes LM, Jianxiong J, et al. Novel polymer-grafted starch microparticles for mucosal delivery of vaccines. Immunology. 1996 May;88(1):162–168.
  • Chattaraj SC, Rathinavelu A, Das SK. Biodegradable microparticles of influenza viral vaccine: comparison of the effects of routes of administration on the in vivo immune response in mice. J Control Release. 1999 Mar 29; 58(2):223–232.
  • Bhowmik T, D’Souza B, Uddin MN, et al. Oral delivery of microparticles containing plasmid DNA encoding hepatitis-B surface antigen. J Drug Target. 2012 May;20(4):364–371.
  • O’Neal CM, Crawford SE, Estes MK, et al. Rotavirus virus-like particles administered mucosally induce protective immunity. J Virol. 1997 Nov;71(11):8707–8717.
  • Jung T, Kamm W, Breitenbach A, et al. 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. 2001 Mar;18(3):352–360.
  • Ren JM, Zou QM, Wang FK, et al. PELA microspheres loaded H. pylori lysates and their mucosal immune response. World J Gastroenterol. 2002 Dec;8(6):1098–1102.
  • Borges O, Tavares J, De Sousa A, et al. Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles. Eur J Pharm Sci. 2007 Dec;32(4–5):278–290.
  • Saluja V, Visser MR, van Roosmalen ML, et al. Gastro-intestinal delivery of influenza subunit vaccine formulation adjuvanted with Gram-positive enhancer matrix (GEM) particles. Eur J Pharm Biopharm. 2010 Nov;76(3):470–474.
  • Mangal S, Pawar D, Agrawal U, et al. Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine. Artif Cells Nanomed Biotechnol. 2014 Feb;42(1):47–57.
  • Mattila JP, Mirandola L, Chiriva-Internati M. Development of a M cell-targeted microparticulate platform, BSK02, for oral immunization against the ovarian cancer antigen, sperm protein 17. J Biomed Mater Res B Appl Biomater. 2019 Jan; 107(1):29–36.
  • Kofler N, Ruedl C, Rieser C, et al. Oral immunization with poly-(D,L-lactide-co-glycolide) and poly-(L-lactic acid) microspheres containing pneumotropic bacterial antigens. Int Arch Allergy Immunol. 1997 Aug;113(4):424–431.
  • Le Buanec H, Vetu C, Lachgar A, et al. Induction in mice of anti-Tat mucosal immunity by the intranasal and oral routes. Biomed Pharmacother. 2001 Jul;55(6):316–320.
  • Dea-Ayuela MA, Rama-Iniguez S, Torrado-Santiago S, et al. Microcapsules formulated in the enteric coating copolymer Eudragit L100 as delivery systems for oral vaccination against infections by gastrointestinal nematode parasites. J Drug Target. 2006 Sep; 14(8):567–575.
  • Akalkotkar A, Tawde SA, Chablani L, et al. Oral delivery of particulate prostate cancer vaccine: in vitro and in vivo evaluation. J Drug Target. 2012 May;20(4):338–346.
  • D’Souza B, Bhowmik T, Shashidharamurthy R, et al. Oral microparticulate vaccine for melanoma using M-cell targeting. J Drug Target. 2012 Feb;20(2):166–173.
  • Tawde SA, Chablani L, Akalkotkar A, et al. Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery. J Control Release. 2016 Aug ;235(235):147–154.
  • Chen Y, Wu J, Wang J, et al. Targeted delivery of antigen to intestinal dendritic cells induces oral tolerance and prevents autoimmune diabetes in NOD mice. Diabetologia. 2018 Jun;61(6):1384–1396.
  • Singh B, Maharjan S, Jiang T, et al. Attuning hydroxypropyl methylcellulose phthalate to oral delivery vehicle for effective and selective delivery of protein vaccine in ileum. Biomaterials. 2015 Aug;59:144–159.
  • O’Hagan DT, McGee JP, Holmgren J, et al. Biodegradable microparticles for oral immunization. Vaccine. 1993;11(2):149–154.
  • Bowersock TL, HogenEsch H, Torregrosa S, et al. Induction of pulmonary immunity in cattle by oral administration of ovalbumin in alginate microspheres. Immunol Lett. 1998 Jan;60(1):37–43.
  • Li TC, Suzaki Y, Ami Y, et al. Protection of cynomolgus monkeys against HEV infection by oral administration of recombinant hepatitis E virus-like particles. Vaccine. 2004 Jan 2; 22(3–4):370–377.
  • Tawde SA, Chablani L, Akalkotkar A, et al. Formulation and evaluation of oral microparticulate ovarian cancer vaccines. Vaccine. 2012 Aug 17; 30(38):5675–5681.
  • Baert K, De Geest BG, De Rycke R, et al. beta-glucan microparticles targeted to epithelial APN as oral antigen delivery system. J Control Release. 2015 Dec 28; 220(Pt A):149–159.
  • Pereira MA, Reboucas JS, Ferraz-Carvalho RS, et al. Poly(anhydride) nanoparticles containing cashew nut proteins can induce a strong Th1 and Treg immune response after oral administration. Eur J Pharm Biopharm. 2018 Jun;127:51–60.
  • Parenky AC, Akalkotkar A, Mulla NS, et al. Harnessing T-cell activity against prostate cancer: a therapeutic microparticulate oral cancer vaccine. Vaccine. 2019 Sep 24; 37(41):6085–6092.
  • Zhu Q, Talton J, Zhang G, et al. Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection. Nat Med. 2012 Aug;18(8):1291–1296.
  • Uddin AN, Bejugam NK, Gayakwad SG, et al. Oral delivery of gastro-resistant microencapsulated typhoid vaccine. J Drug Target. 2009 Aug;17(7):553–560.
  • Wang T, Zou M, Jiang H, et al. Synthesis of a novel kind of carbon nanoparticle with large mesopores and macropores and its application as an oral vaccine adjuvant. Eur J Pharm Sci. 2011 Dec 18; 44(5):653–659.
  • Shuttleworth G, Eckery DC, Awram P. Oral and intraperitoneal immunization with rotavirus 2/6 virus-like particles stimulates a systemic and mucosal immune response in mice. Arch Virol. 2005 Feb; 150(2):341–349.
  • Barhate G, Gautam M, Gairola S, et al. Quillaja saponaria extract as mucosal adjuvant with chitosan functionalized gold nanoparticles for mucosal vaccine delivery: stability and immunoefficiency studies. Int J Pharm. 2013 Jan 30; 441(1–2):636–642.
  • Barhate G, Gautam M, Gairola S, et al. Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment. J Pharm Sci. 2014 Nov;103(11):3448–3456.
  • Kaur M, Malik B, Garg T, et al. Development and characterization of guar gum nanoparticles for oral immunization against tuberculosis. Drug Deliv. 2015 May;22(3):328–334.
  • Du L, Yu Z, Pang F, et al. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses. Front Cell Infect Microbiol. 2018;8:7.
  • Bagheripour MJ, Ebrahimi F, Hajizade A, et al. Immunogenicity evaluation of rBoNT/E nanovaccine after mucosal administration. Iran J Basic Med Sci. 2019 Apr;22(4):353–359.
  • Camacho AI, Irache JM, de Souza J, et al. Nanoparticle-based vaccine for mucosal protection against Shigella flexneri in mice. Vaccine. 2013 Jul 11; 31(32):3288–3294.
  • Luo S, Liu W, Zeng Z, et al. Toxic adjuvants alter the function and phenotype of dendritic cells to initiate adaptive immune responses induced by oral Helicobacter pylori vaccines. Helicobacter. 2018 Dec;23(6):e12536.
  • Akbari MR, Saadati M, Honari H, et al. IpaD-loaded N-trimethyl chitosan nanoparticles can efficiently protect guinea pigs against shigella flexneri. Iran J Immunol. 2019 Sep;16(3):212–224.
  • Eldridge JH, Hammond CJ, Meulbroek JA, et al. Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the peyer’s patches. J Control Release. 1990;11(1–3):205–214.
  • Saeed MI, Omar AR, Hussein MZ, et al. Development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human Enterovirus-71 vaccine encapsulated carrier. Hum Vaccin Immunother. 2015;11(10):2414–2424.
  • Rajkannan R, Arul V, Malar EJ, et al. Preparation, physiochemical characterization, and oral immunogenicity of Abeta(1-12), Abeta(29-40), and Abeta(1-42) loaded PLG microparticles formulations. J Pharm Sci. 2009 Jun; 98(6):2027–2039.
  • Plana-Duran J, Bastons M, Rodriguez MJ, et al. Oral immunization of rabbits with VP60 particles confers protection against rabbit hemorrhagic disease. Arch Virol. 1996;141(8):1423–1436.
  • Shi W, Liu J, Huang Y, et al. Papillomavirus pseudovirus: a novel vaccine to induce mucosal and systemic cytotoxic T-lymphocyte responses. J Virol. 2001 Nov;75(21):10139–10148.
  • Kumar MNVR, Muzzarelli RAA, Muzzarelli C, et al. Chitosan Chemistry and Pharmaceutical Perspectives. Chem Rev. 2004 Dec 01;104(12):6017–6084.
  • Brayden DJ. Oral vaccination in man using antigens in particles: current status. Eur J Pharm Sci. 2001 Jan 01;14(3):183–189.
  • Islam MA, Firdous J, Choi Y-J, et al. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review. Int J Nanomedicine. 2012 December 13;7(7):6077–6093.
  • Jung T, Kamm W, Breitenbach A, et al. Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake? Eur J Pharm Sci. 2000 July 03;50(1):147–160.
  • Hori M, Onishi H, Machida Y. Evaluation of Eudragit-coated chitosan microparticles as an oral immune delivery system. Int J Pharm. 2005 Jun 13; 297(1–2):223–234.
  • van der Lubben IM, Verhoef JC, Borchard G, et al. Chitosan for mucosal vaccination. Adv Drug Deliv Rev. 2001 November 05;52(2):139–144.
  • Sinha VR, Singla AK, Wadhawan S, et al. Chitosan microspheres as a potential carrier for drugs. Int J Pharm. 2004 Apr 15; 274(1–2):1–33.
  • Makadia HK, Siegel SJ. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers (Basel). 2011;3(3):1377–1397.
  • Zeltins A. Construction and Characterization of Virus-Like Particles: a Review. Mol Biotechnol. 2013 Jan 01;53(1):92–107.
  • Bachmann MF, Dyer MR. Therapeutic vaccination for chronic diseases: a new class of drugs in sight [Perspective]. Nat Rev Drug Discov. 2004 Jan 01;3(1):81. online.
  • Bachmann MF, Rohrer UH, Kundig TM, et al. The influence of antigen organization on B cell responsiveness [10.1126/science.8248784]. Science. 1993;262(5138):1448.
  • Takamura S, Niikura M, Li TC, et al. DNA vaccine-encapsulated virus-like particles derived from an orally transmissible virus stimulate mucosal and systemic immune responses by oral administration [Research Article]. Gene Ther. 2004 Feb 19;11(7):628. online.
  • McElrath MJ. Selection of potent immunological adjuvants for vaccine construction. Semin Cancer Biol. 1995 December 01;6(6):375–385.
  • Chen XY, Butt AM, Mohd Amin MCI. Enhanced paracellular delivery of vaccine by hydrogel microparticles-mediated reversible tight junction opening for effective oral immunization. J Control Release. 2019 Oct; 311-312:50–64.
  • Ma T, Wang L, Yang T, et al. M-cell targeted polymeric lipid nanoparticles containing a Toll-like receptor agonist to boost oral immunity. Int J Pharm. 2014 Oct 1; 473(1–2):296–303.
  • Sahu KK, Kaurav M, Pandey RS. Chylomicron mimicking solid lipid nanoemulsions encapsulated enteric minicapsules targeted to colon for immunization against hepatitis B. Int Immunopharmacol. 2019 Jan; 66:317–329.
  • Freytag LC, Clements JD. Mucosal adjuvants. Vaccine. 2005 Mar 7; 23(15):1804–1813.
  • Cohen JA, Beaudette TT, Tseng WW, et al. T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the effect of particle size. Bioconjugate Chem. 2009 Jan;20(1):111–119.
  • Borst J, Ahrends T, Bąbała N, et al. CD4+ T cell help in cancer immunology and immunotherapy. Nat Rev Immunol. 2018 October 01;18(10):635–647.
  • Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. Npj Vaccines. 2019 February 08;4(1):7.
  • Pfaar O, Creticos PS, Kleine-Tebbe J, et al. One Hundred Ten Years of Allergen Immunotherapy: a Broad Look Into the Future. J Allergy Clin Immunol Pract. 2021 May 01;9(5):1791–1803.

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