Current status of mucosal vaccines against SARS-CoV2: a hope for protective immunity

References

• WHO Coronavirus (COVID-19) Dashboard, World Health Organization. [cited 21 Jun 2022] Available from: https://covid19.who.int/
   Google Scholar
• Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020;369(6499):50–54.
   PubMed Web of Science ®Google Scholar
• Coronavirus (COVID-19) Vaccinations, Our World In Data. [cited 21 Jun 2022] Available from: https://ourworldindata.org/covid-vaccinations
   Google Scholar
• Tenforde MW, Self WH, Adams K, et al. Influenza and other viruses in the acutely Ill (IVY) network. association between mRNA vaccination and COVID-19 hospitalization and disease severity. Jama. 2021 Nov 23;326(20):2043–2054.
   PubMed Web of Science ®Google Scholar
• Ibarrondo FJ, Hofmann C, Fulcher JA, et al., Primary, recall, and decay kinetics of SARS-CoV-2 vaccine antibody responses. ACS Nano. 2021;15(7): 11180–11191.
   PubMed Web of Science ®Google Scholar
• Kupferschmidt K. Where did ‘weird’ Omicron come from? Science. 2021;374(6572):1179.
   PubMed Web of Science ®Google Scholar
• Sun S, Cai Y, Song TZ, et al. Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2. Cell Res. 2021;31(9):1011–1023.
   PubMed Web of Science ®Google Scholar
• Jangra S, De Vrieze J, Choi A, et al., Sterilizing Immunity against SARS-CoV-2 infection in mice by a single-shot and lipid amphiphile imidazoquinoline TLR7/8 agonist-adjuvanted recombinant spike protein vaccine. Angew Chem Int Ed Engl. 2021;60(17): 9467–9473. .
   PubMed Web of Science ®Google Scholar
• Mouro V, Fischer A. Dealing with a mucosal viral pandemic: lessons from COVID-19 vaccines. Mucosal Immunol. 2022 Apr;15(4):584–594.
   PubMed Web of Science ®Google Scholar
• Butler SE, Crowley AR, Natarajan H, et al. Distinct features and functions of systemic and mucosal humoral immunity among SARS-CoV-2 convalescent individuals. Front Immunol. 2021 Jan 28;11:618685. doi: 10.3389/fimmu.2020.618685. PMID: 33584712; PMCID: PMC7876222.
   PubMed Web of Science ®Google Scholar
• Russell MW, Mestecky J. Mucosal immunity: the missing link in comprehending SARS-CoV-2 infection and transmission. Front Immunol. 2022 Aug 17;13:957107. DOI:10.3389/fimmu.2022.957107.
   PubMed Web of Science ®Google Scholar
• Kar S, Devnath P, Emran TB, et al. Oral and intranasal vaccines against SARS-CoV-2: current progress, prospects, advantages, and challenges. Immun Inflamm Dis. 2022;10(4):e604.
   PubMed Web of Science ®Google Scholar
• Karczmarzyk K, Kęsik-Brodacka M. Attacking the intruder at the gate: prospects of mucosal anti SARS-CoV-2 vaccines. Pathogens. 2022;11(2):117.
   PubMed Web of Science ®Google Scholar
• Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184(4):861–880.
   PubMed Web of Science ®Google Scholar
• Sun L, Wang X, Saredy J, et al. Innate-adaptive immunity interplay and redox regulation in immune response. Redox Biol. 2020;37:101759.
   PubMed Web of Science ®Google Scholar
• Li M, Wang Y, Sun Y, et al. Mucosal vaccines: strategies and challenges. Immunol Lett. 2020;217:116–125.
   PubMed Web of Science ®Google Scholar
• García-Hernández AL, Rubio-Infante N, Moreno-Fierros L. Mucosal immunology and oral vaccination. In: Rosales-Mendoza S, editor. Genetically engineered plants as a source of vaccines against wide spread diseases. New York: Springer; 2014. p. 15–42.
   Google Scholar
• Rosales-Mendoza S, González-Ortega O. The mucosal immune system: an outlook for nanovaccines development. In: Rosales-Mendoza S, González-Ortega O, editors. Nanovaccines. Cham: Springer; 2019. p. 15–35.
   Google Scholar
• Trincado V, Gala RP, Morales JO. Buccal and sublingual vaccines: a review on oral mucosal immunization and delivery systems. Vaccines (Basel). 2021;9(10):1177.
   PubMed Web of Science ®Google Scholar
• Lavelle EC, Ward RW. Mucosal vaccines - fortifying the frontiers. Nat Rev Immunol. 2022;22(4):236–250.
   PubMed Web of Science ®Google Scholar
• Mörbe UM, Jørgensen PB, Fenton TM, et al. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal Immunol. 2021;14(4):793–802.
   PubMed Web of Science ®Google Scholar
• Komban RJ, Strömberg A, Biram A, et al. Activated Peyer’s patch B cells sample antigen directly from M cells in the subepithelial dome. Nat Commun. 2019;10(1):2423.
   PubMedGoogle Scholar
• Fenton TM, Jørgensen PB, Niss K, et al. Immune profiling of human gut-associated lymphoid tissue identifies a role for isolated lymphoid follicles in priming of region-specific immunity. Immunity. 2020;52(3):557–570.e6.
   PubMed Web of Science ®Google Scholar
• Layhadi JA, Shamji MH. Uncovering the immunological properties of isolated lymphoid follicles. Allergy. 2021;76(4):1292–1293.
   PubMed Web of Science ®Google Scholar
• Jørgensen PB, Fenton TM, Mörbe UM, et al. Identification, isolation and analysis of human gut-associated lymphoid tissues. Nat Protoc. 2021;16(4):2051–2067.
   PubMed Web of Science ®Google Scholar
• Houston SA, Cerovic V, Thomson C, et al. The lymph nodes draining the small intestine and colon are anatomically separate and immunologically distinct. Mucosal Immunol. 2016;9(2):468–478.
   PubMed Web of Science ®Google Scholar
• Lamichhane A, Azegamia T, Kiyonoa H. The mucosal immune system for vaccine development. Vaccine. 2014;32(49):6711–6723.
   PubMed Web of Science ®Google Scholar
• Sepahi A, Salinas I. The evolution of nasal immune systems in vertebrates. Mol Immunol. 2016;69:131–138.
   PubMed Web of Science ®Google Scholar
• Silva-Sanchez A, Randall TD. Anatomical uniqueness of the mucosal immune system (GALT, NALT, iBALT) for the induction and regulation of mucosal immunity and tolerance. In: Kiyono H, Pascual DW, editors. Mucosal Vaccines. Cambridge, MA, USA: Academic Press; 2020 pp. 21–54.• Covers the fundamental knowledge on the mucosal immune system organization and function
   Google Scholar
• Pabst R. Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)-Structure, function and species differences. Vaccine. 2015;33(36):4406–4413.
   PubMed Web of Science ®Google Scholar
• Cai L, Xu H, Cui Z. Factors limiting the translatability of rodent model-based intranasal vaccine research to humans. AAPS PharmSciTech. 2022 Jul 12;23(6):191.
   PubMed Web of Science ®Google Scholar
• Kiyono H, Fukuyama S. NALT- versus Peyer’s-patch-mediated mucosal immunity. Nat Rev Immunol. 2004;4(9):699–710.
   PubMed Web of Science ®Google Scholar
• Date Y, Ebisawa M, Fukuda S, et al. NALT M cells are important for immune induction for the common mucosal immune system. Int Immunol. 2017;29(10):471–478.
   PubMed Web of Science ®Google Scholar
• Lee H, Ruane D, Law K, et al. Phenotype and function of nasal dendritic cells. Mucosal Immunol. 2015 Sep;8(5):1083–1098.
   PubMed Web of Science ®Google Scholar
• Takaki H, Ichimiya S, Matsumoto M, et al. Mucosal immune response in nasal-associated lymphoid tissue upon intranasal administration by adjuvants. J Innate Immun. 2018;10(5–6):515–521.
   PubMed Web of Science ®Google Scholar
• Russell MW, Mestecky J, Strober Wet al. Overview: The mucosal immune system . In: Mucosal Immunol. 4th edition, Cambridge, MA, USA: Academic Press. 2015-p. 3–8.
   Google Scholar
• Kurono Y. The mucosal immune system of the upper respiratory tract and recent progress in mucosal vaccines. Auris Nasus Larynx. 2022;49(1):1–10.
   PubMed Web of Science ®Google Scholar
• Kim SH, Jang YS. The development of mucosal vaccines for both mucosal and systemic immune induction and the roles played by adjuvants. Clin Exp Vaccine Res. 2017;6(1):15–21.
   PubMed Web of Science ®Google Scholar
• Boyaka PN. Inducing mucosal IgA: a challenge for vaccine adjuvants and delivery systems. J Immunol. 2017;199(1):9–16.
   PubMed Web of Science ®Google Scholar
• Duverger A, Jackson RJ, van Ginkel FW, et al. Bacillus anthracis edema toxin acts as an adjuvant for mucosal immune responses to nasally administered vaccine antigens. J Immunol. 2006;176(3):1776–1783.
   PubMed Web of Science ®Google Scholar
• Clements JD, Hartzog NM, Lyon FL. Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens. Vaccine. 1988;6(3):269–277.
   PubMed Web of Science ®Google Scholar
• Elson CO, Ealding W. Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen. J Immunol. 1984;133(6):2892–2897.
   PubMed Web of Science ®Google Scholar
• Elson CO, Ealding W. Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. J Immunol. 1984;132(6):2736–2741.
   PubMed Web of Science ®Google Scholar
• Boyaka PN, Ohmura M, Fujihashi K, et al. Chimeras of labile toxin one and cholera toxin retain mucosal adjuvanticity and direct Th cell subsets via their B subunit. J Immunol. 2003;170(1):454–462.
   PubMed Web of Science ®Google Scholar
• Banerjee S, Medina-Fatimi A, Nichols R, et al. Safety and efficacy of low dose Escherichia coli enterotoxin adjuvant for urease based oral immunisation against Helicobacter pylori in healthy volunteers. Gut. 2002;51(5):634–640.
   PubMed Web of Science ®Google Scholar
• Mutsch M, Zhou W, Rhodes P, et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. N Engl J Med. 2004;350(9):896–903.
   PubMed Web of Science ®Google Scholar
• Clements JD, Norton EB. The mucosal vaccine adjuvant LT(R192G/L211A) or dmLT. mSphere. mSphere. 2018;3(4):e00215–18.
   PubMed Web of Science ®Google Scholar
• Abusleme L, Moutsopoulos NM. IL-17: overview and role in oral immunity and microbiome. Oral Dis. 2017;23(7):854–865.
   PubMed Web of Science ®Google Scholar
• 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;36(40): 5990–5998. .
   PubMed Web of Science ®Google Scholar
• Xie W, Zhao W, Zou Z, et al. Oral multivalent epitope vaccine, based on UreB, HpaA, CAT, and LTB, for prevention and treatment of Helicobacter pylori infection in C57BL/6 mice. Helicobacter. 2021;26(3):e12807.
   PubMed Web of Science ®Google Scholar
• Pitcovski J, Gruzdev N, Abzach A, et al., Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine. Vaccine. 2022;40(8): 1098–1107.
   PubMed Web of Science ®Google Scholar
• Burdette DL, Monroe KM, Sotelo-Troha K, et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 2011;478(7370):515–518
   PubMed Web of Science ®Google Scholar
• Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature. 2009;461(7265):788–792.
   PubMed Web of Science ®Google Scholar
• Blaauboer SM, Mansouri S, Tucker HR, et al. The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo. Elife. 2015;4:e06670.
   PubMed Web of Science ®Google Scholar
• Jiang W, Wang X, Su Y, et al. Intranasal immunization with a c-di-GMP-adjuvanted acellular pertussis vaccine provides superior immunity against bordetella pertussis in a mouse model. Front Immunol. 2022;13:878832.
   PubMed Web of Science ®Google Scholar
• Uematsu S, Fujimoto K, Jang MH, et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol. 2008;9(7):769–776.
   PubMed Web of Science ®Google Scholar
• Chen CH, Chen CC, Wang WB, et al. Intranasal immunization with zika virus envelope domain III-flagellin fusion protein elicits systemic and mucosal immune responses and protection against subcutaneous and intravaginal virus challenges. Pharmaceutics. 2022;14(5):1014.
   PubMed Web of Science ®Google Scholar
• Lai CH, Tang N, Jan JT, et al. Use of recombinant flagellin in oil-in-water emulsions enhances hemagglutinin-specific mucosal IgA production and IL-17 secreting T cells against H5N1 avian influenza virus infection. Vaccine. 2015;33(35):4321–4329.
   PubMed Web of Science ®Google Scholar
• Tateishi K, Fujihashi K, Yamamoto N, et al. CpG ODN G9.1 as a novel nasal ODN adjuvant elicits complete protection from influenza virus infection without causing inflammatory immune responses. Vaccine. 2019;37(36):5382–5389.
   PubMed Web of Science ®Google Scholar
• Zhang HX, Qiu YY, Zhao YH, et al. Immunogenicity of oral vaccination with Lactococcus lactis derived vaccine candidate antigen (UreB) of Helicobacter pylori fused with the human interleukin 2 as adjuvant. Mol Cell Probes. 2014;28(1):25–30.
   PubMed Web of Science ®Google Scholar
• Ma F, Zhang Q, Zheng L. Interleukin/chitosan (JY) adjuvant enhances the mucosal immunity of human papillomavirus 16 L1 virus-like particles in mice. Biotechnol Lett. 2015;37(4):773–777.
   PubMed Web of Science ®Google Scholar
• Lapuente D, Storcksdieck Genannt Bonsmann M, Maaske A, et al. IL-1β as mucosal vaccine adjuvant: the specific induction of tissue-resident memory T cells improves the heterosubtypic immunity against influenza A viruses. Mucosal Immunol. 2018;11(4):1265–1278.
   PubMed Web of Science ®Google Scholar
• King RG, Silva-Sanchez A, Peel JN, et al. Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice. Vaccines. 2021;9(8):881 . DOI: 10.3390/vaccines9080881.
   Web of Science ®Google Scholar
• Bricker TL, Darling TL, Hassan AO, et al., A single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters. Cell Rep. 2021;36(3): 109400. .
   PubMed Web of Science ®Google Scholar
• van Doremalen N, Purushotham JN, Schulz JE, et al., Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models. Sci Transl Med. 2021;13(607): eabh0755. .
   PubMed Web of Science ®Google Scholar
• An D, Li K, Rowe DK, et al., Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5-based COVID-19 vaccine. Sci Adv. 2021;7(27): eabi5246.
   PubMed Web of Science ®Google Scholar
• Park JG, Oladunni FS, Rohaim MA, et al., Immunogenicity and protective efficacy of an intranasal live-attenuated vaccine against SARS-CoV-2. iScience. 2021;24(9): 102941.
   PubMed Web of Science ®Google Scholar
• Ku MW, Bourgine M, Authié P, et al. Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models. Cell Host Microbe. 2021;29(2):236–249.e6.
   PubMed Web of Science ®Google Scholar
• Wu S, Zhong G, Zhang J, et al. A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge. Nat Commun. 2020 14;11(1):4081. .
   PubMed Web of Science ®Google Scholar
• Xu F, Wu S, Yi L, et al. Safety, mucosal and systemic immunopotency of an aerosolized adenovirus-vectored vaccine against SARS-CoV-2 in rhesus macaques. Emerg Microbes Infect. 2022;11(1):438–441.
   PubMed Web of Science ®Google Scholar
• Hassan AO, Kafai NM, Dmitriev IP, et al., A single-dose intranasal chad vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell. 2020;183(1): 169–184.e13.
   PubMed Web of Science ®Google Scholar
• Hassan AO, Feldmann F, Zhao H, et al. A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. doi: 10.1101/2021.01.26.428251. bioRxiv Preprint
   Google Scholar
• Hassan AO, Shrihari S, Gorman MJ, et al. An intranasal vaccine durably protects against SARS-CoV-2 variants in mice. Cell Rep. 2021;36(4):109452.
   PubMed Web of Science ®Google Scholar
• Lapuente D, Fuchs J, Willar J, et al., Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization. Nat Commun. 2021;12(1): 6871.
   PubMed Web of Science ®Google Scholar
• Mudrick HE, McGlinch EB, Parrett BJ, et al. Comparison of mucosal and intramuscular immunization against SARS-CoV-2 with replication-defective and replicating single-cycle adenovirus vaccines. bioRxiv Prepritnt. DOI:10.1101/2021.04.20.440651
   Google Scholar
• Chandrasekar SS, Phanse Y, Hildebrand RE, et al. Localized and systemic immune responses against SARS-CoV-2 following mucosal immunization. Vaccines (Basel). 2021;9(2):132.
   PubMed Web of Science ®Google Scholar
• Zhou R, Wang P, Wong YC, et al. Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models. EBioMedicine. 2022;75:103762.
   PubMed Web of Science ®Google Scholar
• Kumar US, Afjei R, Ferrara K, et al. Gold-nanostar-chitosan-mediated delivery of SARS-CoV-2 DNA vaccine for respiratory mucosal immunization: development and proof-of-principle. ACS Nano. 2021;27:acsnano.1c05002. •• Presents an innovative mucosal nanovaccine against COVID-19.
   Google Scholar
• Ashhurst A, Johansen M, Maxwell J, et al. Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice. Nat Commun. 2022;13(1): 1–18 . doi: 10.1038/s41467-022-34297-3.
   PubMed Web of Science ®Google Scholar
• Sui Y, Li J, Zhang R, et al. Protection against SARS-CoV-2 infection by a mucosal vaccine in rhesus macaques. JCI Insight. 2021;6(10):e148494.
   PubMed Web of Science ®Google Scholar
• Zhuo SH, Wu JJ, Zhao L, et al. A chitosan-mediated inhalable nanovaccine against SARS-CoV-2. Nano Res. 2022;15(5):4191–4200.
   PubMed Web of Science ®Google Scholar
• Jearanaiwitayakul T, Seesen M, Chawengkirttikul R, et al. Intranasal administration of RBD nanoparticles confers induction of mucosal and systemic immunity against SARS-CoV-2. Vaccines (Basel). 2021;9(7):768.
   PubMed Web of Science ®Google Scholar
• Jiang L, Driedonks TAP, Jong WSP, et al. A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants. , J Extracell Vesicles. 2022;11(3): e12192 . doi: 10.1002/jev2.12192.
   PubMed Web of Science ®Google Scholar
• Du Y, Xu Y, Feng J, et al. Intranasal administration of a recombinant RBD vaccine induced protective immunity against SARS-CoV-2 in mouse. Vaccine. 2021;39(16):2280–2287.
   PubMed Web of Science ®Google Scholar
• Zheng B, Peng W, Guo M, et al. Inhalable nanovaccine with biomimetic coronavirus structure to trigger mucosal immunity of respiratory tract against COVID-19. Chem Eng J. 2021;418:129392.
   PubMed Web of Science ®Google Scholar
• Ilinykh PA, Periasamy S, Huang K, et al. A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and memory T cell response in the lungs and protects hamsters against SARS-CoV-2. NPJ Vaccines. 2022;7(1):47.
   PubMed Web of Science ®Google Scholar
• Vesin B, Lopez J, Noirat A, et al. An intranasal lentiviral booster reinforces the waning mRNA vaccine-induced SARS-CoV-2 immunity that it targets to lung mucosa. Mol Ther. 2022;27:S1525-0016(22)00245–3. •• Applies the concept of boosting by mucosal routes.
   Google Scholar
• Jacob-Dolan C, Barouch DH. COVID-19 vaccines: adenoviral vectors. Annu Rev Med. 2022;73(1):41–54.
   PubMedGoogle Scholar
• Chang J. Adenovirus vectors: excellent tools for vaccine development. Immune Netw. 2021;21(1):e6.
   PubMed Web of Science ®Google Scholar
• Afolabi MO, Ishola D, Manno D, et al. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2022;22(1):110–122.
   PubMed Web of Science ®Google Scholar
• Ishola D, Manno D, Afolabi MO, et al. Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial. Lancet Infect Dis. 2022;22(1):97–109.
   PubMed Web of Science ®Google Scholar
• Vela Ramirez JE, Sharpe LA, Peppas NA. Current state and challenges in developing oral vaccines. Adv Drug Deliv Rev. 2017;114:116–131.
   PubMed Web of Science ®Google Scholar
• Miteva D, Peshevska-Sekulovska M, Snegarova V, et al. Mucosal COVID-19 vaccines: risks, benefits and control of the pandemic. World J Virol. 2022 Sep 25;11(5):221–236.
   PubMedGoogle Scholar
• Date AA, Hanes J, Ensign LM. Nanoparticles for oral delivery: design, evaluation and state-of-the-art. J Control Release. 2016;240:504–526.
   PubMed Web of Science ®Google Scholar
• Sung JC, Liu Y, Wu KC, et al., Expression of SARS-CoV-2 spike protein receptor binding domain on recombinant B. subtilis on spore surface: a potential COVID-19 oral vaccine candidate. Vaccines (Basel). 2021;10(1):2.
   PubMed Web of Science ®Google Scholar
• Peng KW, Carey T, Lech P, et al. Boosting of SARS-CoV-2 immunity in nonhuman primates using an oral rhabdoviral vaccine. Vaccine. 2022;40(15):2342–2351.
   PubMed Web of Science ®Google Scholar
• Johnson S, Martinez CI, Tedjakusuma SN, et al., Oral vaccination protects against severe acute respiratory syndrome coronavirus 2 in a Syrian hamster challenge model. J Infect Dis. 2022;225(1):34–41.
   PubMed Web of Science ®Google Scholar
• Langel SN, Jhonson SJ, Martinez CI, et al. Oral and intranasal Ad5 SARS-CoV-2 vaccines decrease disease and viral transmission in a golden hamster model. doi: 10.1101/2021.10.03.462919. bioRxiv preprint
   Google Scholar
• Gao T, Ren Y, Li S, et al. Immune response induced by oral administration with a Saccharomyces cerevisiae-based SARS-CoV-2 vaccine in mice. Microb Cell Fact. 2021;20(1):95.
   PubMed Web of Science ®Google Scholar
• Jawalagatti V, Kirthika P, Hewawaduge C, et al. Bacteria-enabled oral delivery of a replicon-based mRNA vaccine candidate protects against ancestral and delta variant SARS-CoV-2. Mol Ther. 2022;30(5):1926–1940.
   PubMed Web of Science ®Google Scholar
• Sahdev P, Ochyl LJ, Moon JJ. Biomaterials for nanoparticle vaccine delivery systems. Pharm Res. 2014;31(10):2563–2582.
   PubMed Web of Science ®Google Scholar
• Donaldson B, Lateef Z, Walker GF, et al. Virus-like particle vaccines: immunology and formulation for clinical translation. Expert Rev Vaccines. 2018;17(9):833–849.
   PubMed Web of Science ®Google Scholar
• Du J, Zhang YS, Hobson D, et al. Nanoparticles for immune system targeting. Drug Discov Today. 2017;22(9): 1295–1301.
   PubMed Web of Science ®Google Scholar
• Tonigold M, Mailänder V. Endocytosis and intracellular processing of nanoparticles in dendritic cells: routes to effective immunonanomedicines. Nanomedicine (Lond). 2016;11(20):2625–2630.
   PubMed Web of Science ®Google Scholar
• Lee WH, Loo CY, Traini D, et al. Nano- and micro-based inhaled drug delivery systems for targeting alveolar macrophages. Expert Opin Drug Deliv. 2015;12(6):1009–1026.
   PubMed Web of Science ®Google Scholar
• Blank F, Fytianos K, Seydoux E, et al. Interaction of biomedical nanoparticles with the pulmonary immune system. J Nanobiotechnology. 2017;15(1):6.
   PubMedGoogle Scholar
• Salatin S, Maleki Dizaj S, Yari Khosroushahi A. Effect of the surface modification, size, and shape on cellular uptake of nanoparticles. Cell Biol Int. 2015;39(8):881–890.
   PubMed Web of Science ®Google Scholar
• Sheng Y, Liu C, Yuan Y, et al. Long-circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water-soluble chitosan. Biomaterials. 2009;30(12):2340–2348.
   PubMed Web of Science ®Google Scholar
• Swaminathan G, Thoryk EA, Cox KS, et al. A novel lipid nanoparticle adjuvant significantly enhances B cell and T cell responses to sub-unit vaccine antigens. Vaccine. 2016;34(1):110–119.
   PubMed Web of Science ®Google Scholar
• Khutoryanskiy VV. Advances in mucoadhesion and mucoadhesive polymers. Macromol Biosci. 2011;11(6):748–764.
   PubMed Web of Science ®Google Scholar
• Preston KB, Randolph TW. Stability of lyophilized and spray dried vaccine formulations. Adv Drug Deliv Rev. 2021;171:50–61.
   PubMed Web of Science ®Google Scholar
• Bahamondez-Canas TF, Cui Z. Intranasal immunization with dry powder vaccines. Eur J Pharm Biopharm. 2018;122:167–175.
   PubMed Web of Science ®Google Scholar