Oral and nasal vaccination

current prospects, challenges, and impact of nanotechnology-based delivery systems





Mucosal vaccination; Oral vaccine; Nasal vaccine; Nanocarriers; Nano-vaccinology


Currently, mucosal vaccine administration has stood out as an easier and non-invasive application method. It can also be used to induce local and systemic immune responses. In the COVID-19 pandemic context, nasal and oral vaccines have been developed based on different technological platforms. This review addressed relevant aspects of mucosal vaccine administration, with emphasis on oral and nasal vaccinations, in addition to the importance of using nanotechnology-based delivery systems to enable these strategies.


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Afrough B, Dowall S, Hewson R. Emerging viruses and current strategies for vaccine intervention. Clin Exp Immunol. 2019;196(2):157-166.

Apolinário AC, Salata GC, Bianco AFR, Fukumori C, Lopes LB. Abrindo a caixa de pandora dos nanomedicamentos: há realmente muito mais ‘espaço lá embaixo’. Quím Nova. 2020;43(2): 212-225.

Ashraf MU, Kim Y, Kumar S, Seo D, Ashraf M, Bae YS. COVID-19 Vaccines (Revisited) and oral-mucosal vector system as a potential vaccine platform. Vaccines (Basel). 2021;9(2):171.

Boushehri MAS, Dietrich D, Lamprecht A. Nanotechnology as a platform for the development of injectable parenteral formulations: a comprehensive review of the know-hows and state of the art. Pharmaceutics. 2020;12(6):510.

Braz L, Guimarães DT, Vaz MRF, Nóbrega FF, de F. Contributions of biotechnology in the development and production of first, second and third generation vaccines. Rev Health Sci. 2014;3(30):189-206.

Caetano LA, Almeida AJ, Gonćalves LM. Approaches to tuberculosis mucosal vaccine development using nanoparticles and microparticles: a review. J Biomed Nanotechnol. 2014;10(9):2295-316.

Coffey JW, Gaiha GD, Traverso G. Oral biologic delivery: advances toward oral subunit, DNA, and mRNA vaccines and the potential for mass vaccination during pandemics. Annu Rev Pharmacol Toxicol. 2021;61:517-540.

Contera S, Bernardino JS, Tetley TD. Biotechnology, nanotechnology and medicine. Emerg Top Life Sci. 2020;4(6):551-554.

Corthésy B, Bioley G. Lipid-based particles: versatile delivery systems for mucosal vaccination against infection. Front Immunol. 2018;9:431.

Davitt CJ, Lavelle EC. Delivery strategies to enhance oral vaccination against enteric infections. Adv Drug Deliv Rev. 2015;91:52-69.

De Magistris MT. Mucosal delivery of vaccine antigens and its advantages in pediatrics. Adv Drug Deliv Rev . 2006;58(1):52-67.

Diniz MDO, Ferreira LCS. Biotechnology applied to the development of vaccines. Estudos Avançados. 2010;24(70):19-30.

Du Y, Xu Y, Feng J, Hu L, Zhang Y, Zhang B, et al. Intranasal administration of a recombinant RBD vaccine-induced protective immunity against SARS-CoV-2 in mouse. Vaccine. 2021;39(16):2280-2287.

Fernandes J, Lanzarini NM, Homma A, Lemos ERS. Vaccines. Rio de Janeiro: Editora Fiocruz, 2021.

Fries CN, Curvino EJ, Chen JL, Permar SR, Fouda GG, Collier JH. Advances in nanomaterial vaccine strategies to address infectious diseases impacting global health. Nat Nanotechnol. 2021;16(4):1-14.

Govindaraju K, Dilip Itroutwar P, Veeramani V, Ashok Kumar T, Tamilselva S. Application of nanotechnology in diagnosis and disease management of White Spot Syndrome Virus (WSSV) in aquaculture. J Clust Sci. 2020;31:1163- 1171.

Han HJ, Nwagwu C, Anyim O, Ekweremadu C, Kim S. COVID-19 and cancer: From basic mechanisms to vaccine development using nanotechnology. Int Immunopharmacol. 2021;90:107247.

Illum L. Nanoparticulate systems for nasal delivery of drugs: a real improvement over simple systems? J Pharm Sci. 2007;96(3):473-83.

Islam MA, Firdous J, Choi YJ, Yun CH, Cho CS. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review. Int J Nanomed. 2012;7:6077-93.

Jia Y, Krishnan L, Omri A. Nasal and pulmonary vaccine delivery using particulate carriers. Expert Opin Drug Deliv. 2015;12(6):993-1008.

Jiao H, Yang H, Zhao D, Chen J, Zhang Q, Liang J, et al. Design and immune characterization of a novel Neisseria gonorrhoeae DNA vaccine using bacterial ghosts as vector and adjuvant. Vaccine. 2018;36(30):4532-4539.

Jin Z, Gao S, Cui X, Sun D, Zhao K. Adjuvants and delivery systems based on polymeric nanoparticles for mucosal vaccines. Int J Pharm. 2019;572:118731.

Jiskoot W, Kersten GFA, Mastrobattista E. Vaccines. Pharm Biotechnol. 2013;27:439-457.

Kalam MA, Khan AA, Alshamsan A. Non-invasive administration of biodegradable nano-carrier vaccines. Am J Transl Res. 2017;9(1):15-35.

Kang SH, Hong SJ, Lee YK, Cho S. Oral vaccine delivery for intestinal immunity-biological basis, barriers, delivery system, and M cell targeting. Polymers (Basel). 2018;10(9):948.

Kang ML, Cho CS, Yoo HS. Application of chitosan microspheres for nasal delivery of vaccines. Biotechnol Adv. 2009;27(6):857-865.

Köping-Höggård M, Sánchez A, Alonso MJ. Nanoparticles as carriers for nasal vaccine delivery. Expert Rev Vaccines. 2005;4(2):185-96.

Kour P, Rath G, Sharma G, Goyal AK. Recent advancement in nanocarriers for oral vaccination. Artif Cells Nanomed Biotechnol. 2018;46( Sup3):S1102-S1114.

Li M, Zhao M, Fu Y, Li Y, Gong T, Zhang Z, et al. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways. J Controlled Release. 2016;228:9-19.

Li YD, Chi WY, Su JH, Ferrall L, Hung CF, Wu TC. Coronavirus vaccine development: from SARS and MERS to COVID-19. J Biomed Sci. 2020;27(1):104.

Marasini N, Skwarczynski M, Toth I. Intranasal delivery of nanoparticle-based vaccines. Ther Deliv. 2017;8(3):151-167.

Mato LY. Nasal route for vaccine and drug delivery: Features and current opportunities. Int J Pharm . 2019;572:118813.

Mehrabi M, Montazeri H, Mohamadpour Dounighi N, Rashti A, Vakili-Ghartavol R. Chitosan-based nanoparticles in mucosal vaccine delivery. Arch Razi Inst. 2018;73(3):165-176.

Negahdaripour M, Golkar N, Hajighahramani N, Kianpour S, Nezafat N, Ghasemi Y. Harnessing self-assembled peptide nanoparticles in epitope vaccine design. Biotechnol Adv. 2017;35(5):575-596.

New RRC. Formulation technologies for oral vaccines. Clin Exp Immunol . 2019;198(2):153-169.

Pan L, Zhang Z, Lv J, Zhou P, Hu W, Fang Y, et al. 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 Nanomed. 2014;9:5603-18.

Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov. 2018;17(4):261-279.

Parker EP, Ramani S, Lopman BA, Church JA, Iturriza-Gómara M, Prendergast AJ, et al. Causes of impaired oral vaccine efficacy in developing countries. Future Microbiol. 2018;13(1):97-118.

Rai M, Bonde S, Yadav A, Plekhanova Y, Reshetilov A, Gupta I, et al. Nanotechnology-based promising strategies for the management of COVID-19: current development and constraints. Expert Rev Anti-infect Ther. 2020;20(10):1299-1308.

Rhee JH. Current and new approaches for mucosal vaccine delivery. Mucosal Vaccines. 2020:325-56.

Riese P, Sakthivel P, Trittel S, Guzmán CA. Intranasal formulations: promising strategy to deliver vaccines. Expert Opin Drug Deliv . 2014;11(10):1619-34.

Rockwell PG. (Ed.). Vaccine science and immunization guideline: a practical guide for primary care. Cham: Springer International Publishing, 2017.

Roco MC. Nanotechnology: convergence with modern biology and medicine. Curr Opin Biotechnol. 2003;14(3):337-46.

Sasso E, D’Alise AM, Zambrano N, Scarselli E, Folgori A, Nicosia A. New viral vectors for infectious diseases and cancer. Semin Immunol. 2020;50:101430.

Shahiwala A, Vyas TK, Amiji MM. Nanocarriers for systemic and mucosal vaccine delivery. Recent Pat Drug Deliv Formul. 2007;1(1):1-9.

Skwarczynski M, Toth I. Non-invasive mucosal vaccine delivery: advantages, challenges and the future. Expert Opin Drug Deliv . 2020;17(4):435-437.

Srivastava A, Gowda DV, Madhunapantula SV, Shinde CG, Iyer M. Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles. APMIS. 2015;123(4):275-88.

Thakur A, Foged C. Nanoparticles for mucosal vaccine delivery. Nanoeng Biomater Adv Drug Delivery. 2020:603-46.

Tlaxca JL, Ellis S, Remmele RL Jr. Live attenuated and inactivated viral vaccine formulation and nasal delivery: potential and challenges. Adv Drug Delivery Rev. 2015;93: 56-78.

Van der Weken H, Cox E, Devriendt B. Advances in oral subunit vaccine design. Vaccines (Basel) . 2020;9(1):1.

Vela Ramirez JE, Sharpe LA, Peppas NA. Current state and challenges in developing oral vaccines. Adv Drug Delivery Rev . 2017;114:116-131.

Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M. Understanding modern-day vaccines: what you need to know. Ann Med. 2018;50(2):110-120.

Wallis J, Shenton DP, Carlisle RC. Novel approaches for the design, delivery and administration of vaccine technologies. Clin Exp Immunol . 2019;196(2):189-204.

Woodrow KA, Bennett KM, Lo DD. Mucosal vaccine design and delivery. Annu Rev Biomed Eng. 2012;14:17-46. Epub. 2012 Apr 18.

Yusuf H, Kett V. Current prospects and future challenges for nasal vaccine delivery. Hum Vaccin Immunother. 2017;13(1):34-45.

Zhang R, Billingsley MM, Mitchell MJ. Biomaterials for vaccine-based cancer immunotherapy. J Controlled Release . 2018a;292:256-276.

Zhang L, Yang W, Hu C, Wang Q, Wu Y. Properties and applications of nanoparticle/microparticle conveyors with adjuvant characteristics suitable for oral vaccination. Int J Nanomed. 2018b;13:2973-2987.

Zhang Y, Li M, Du G, Chen X, Sun X. Advancedoral vaccine delivery strategies for improving the immunity. Adv Drug Deliv Rev . 2021 Oct;177:113928.

Zheng Z, Diaz-Arévalo D, Guan H, Zeng M. Noninvasive vaccination against infectious diseases. Hum Vaccin Immunother . 2018;14(7):1717-1733.

Zhou J, Kroll AV, Holay W, Fang RH, Zhang L. Biomimetic nanotechnology toward personalized vaccines. Adv Mater. 2019;32(13):1901255.

Zhu M, Wang R, Nie G. Applications of nanomaterials as vaccine adjuvants. Hum Vaccin Immunother . 2014;10 (9):2761-2774.




How to Cite

Paiva, N. F., & Vicentini, F. (2023). Oral and nasal vaccination: current prospects, challenges, and impact of nanotechnology-based delivery systems. Brazilian Journal of Pharmaceutical Sciences, 59, e21769. https://doi.org/10.1590/s2175-97902023e21769