Skip to content
2000
image of Nasal Vaccine: A Special Prominence on SARS-CoV-2

Abstract

Nasal administration of mucosal medications and vaccines is an alternate and promising method of drug and vaccine delivery. Mucosal pathways can be used selectively for various disorders due to many benefits. Many initiatives are now being made to yield effective medications and cutting-edge nasal delivery systems. The structure of the nasal cavity and key features were discussed in this review. With a focus on vaccine distribution, the benefits, successes, and difficulties of using the nasal route for medical purposes were examined. The strong result supports the benefits and security, of the safety of nasal medication and vaccination administration. This alternate path may help many unmet medical needs and may also make big vaccination drives or expensive, protracted chronic therapies possible. Today, despite some lingering criticism, the area of nasal medicine and vaccine delivery is expanding quickly, supported by recent advancements in nanotechnology, imaging, and administration devices. The variety of drugs that have been licensed for nasal delivery is expected to increase significantly.

Loading

Article metrics loading...

/content/journals/covid/10.2174/0126667975293193240826093456
2024-10-09
2024-11-22
Loading full text...

Full text loading...

References

  1. Macht D. The history of intravenous and subcutaneous administration of drugs. J. Am. Med. Assoc. 1916 LXVI 12 856 860 10.1001/jama.1916.02580380006003
    [Google Scholar]
  2. Norn S Kruse PR Kruse E Traek af injektionens historie [On the history of injection]. Dan Medicinhist Arbog. 2006 34 104 13
    [Google Scholar]
  3. Barsoum N. Kleeman C. Now and then, the history of parenteral fluid administration. Am. J. Nephrol. 2002 22 2-3 284 289 10.1159/000063775 12097754
    [Google Scholar]
  4. Shakya A.K. Chowdhury M.Y.E. Tao W. Gill H.S. Mucosal vaccine delivery: Current state and a pediatric perspective. J. Control. Release 2016 240 394 413 10.1016/j.jconrel.2016.02.014 26860287
    [Google Scholar]
  5. Kraehenbuhl J.P. Neutra M. Mucosal vaccines: Where do we stand? Curr. Top. Med. Chem. 2013 13 20 2609 2628 10.2174/15680266113136660186 24066889
    [Google Scholar]
  6. Baker J.R. Jr Farazuddin M. Wong P.T. O’Konek J.J. The unfulfilled potential of mucosal immunization. J. Allergy Clin. Immunol. 2022 150 1 1 11 10.1016/j.jaci.2022.05.002 35569567
    [Google Scholar]
  7. Czerkinsky C. Holmgren J. Topical immunization strategies. Mucosal Immunol. 2010 3 6 545 555 10.1038/mi.2010.55 20861833
    [Google Scholar]
  8. Sangolkar S.S. Adhao V.S. Mundhe D.G. Sawarkar H.S. Particle size determination of nasal drug delivery system: A review. Int. J. Pharm. Sci. Rev. Res. 2012 17 1 66 73 https://globalresearchonline.net/journalcontents/v17-1/14.pdf
    [Google Scholar]
  9. Fortuna A. Alves G. Serralheiro A. Sousa J. Falcão A. Intranasal delivery of systemic-acting drugs: Small-molecules and biomacromolecules. Eur. J. Pharm. Biopharm. 2014 88 1 8 27 10.1016/j.ejpb.2014.03.004 24681294
    [Google Scholar]
  10. Beule A.G. Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses. GMS Curr. Top. Otorhinolaryngol. Head Neck Surg. 2010 9 Doc07 10.3205/cto000071 22073111
    [Google Scholar]
  11. Wilson W.R. Allansmith M.R. Rapid, atraumatic method for obtaining nasal mucus samples. Ann. Otol. Rhinol. Laryngol. 1976 85 3 391 393 10.1177/000348947608500311 937966
    [Google Scholar]
  12. Pires A. Fortuna A. Alves G. Falcão A. Intranasal drug delivery: How, why and what for? J. Pharm. Pharm. Sci. 2009 12 3 288 311 10.18433/J3NC79 20067706
    [Google Scholar]
  13. Cole P. Nasal and oral airflow resistors. Site, function, and assessment. Arch. Otolaryngol. Head Neck Surg. 1992 118 8 790 793 10.1001/archotol.1992.01880080012004 1642827
    [Google Scholar]
  14. Sarkar M.A. Drug metabolism in the nasal mucosa. Pharm. Res. 1992 9 1 1 9 10.1023/A:1018911206646 1589391
    [Google Scholar]
  15. Marasini N. Skwarczynski M. Toth I. Intranasal delivery of nanoparticle-based vaccines. Ther. Deliv. 2017 8 3 151 167 10.4155/tde‑2016‑0068 28145824
    [Google Scholar]
  16. Marttin E. Schipper N.G.M. Verhoef J.C. Merkus F.W.H.M. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv. Drug Deliv. Rev. 1998 29 1-2 13 38 10.1016/S0169‑409X(97)00059‑8 10837578
    [Google Scholar]
  17. Alsarra I.A. Hamed A.Y. Alanazi F.K. El Maghraby G.M. Vesicular Systems for Intranasal Drug Delivery. Drug Delivery to the Central Nervous System. Neuromethods. Jain K. Humana Press Vol. 45 10.1007/978‑1‑60761‑529‑3_8
    [Google Scholar]
  18. Csaba N. Garcia-Fuentes M. Alonso M.J. Nanoparticles for nasal vaccination. Adv. Drug Deliv. Rev. 2009 61 2 140 157 10.1016/j.addr.2008.09.005 19121350
    [Google Scholar]
  19. Hjelm B.E. Kilbourne J. Herbst-Kralovetz M.M. TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines. Hum. Vaccin. Immunother. 2014 10 2 410 416 10.4161/hv.27147 24280723
    [Google Scholar]
  20. Fukuyama S. Hiroi T. Yokota Y. Rennert P.D. Yanagita M. Kinoshita N. Terawaki S. Shikina T. Yamamoto M. Kurono Y. Kiyono H. Initiation of NALT organogenesis is independent of the IL-7R, LTbetaR, and NIK signaling pathways but requires the Id2 gene and CD3(-)CD4(+)CD45(+) cells. Immunity 2002 17 1 31 40 10.1016/S1074‑7613(02)00339‑4 12150889
    [Google Scholar]
  21. Kiyono H. Fukuyama S. NALT- versus PEYER’S-patch-mediated mucosal immunity. Nat. Rev. Immunol. 2004 4 9 699 710 10.1038/nri1439 15343369
    [Google Scholar]
  22. Liang B. Hyland L. Hou S. Nasal-associated lymphoid tissue is a site of long-term virus-specific antibody production following respiratory virus infection of mice. J. Virol. 2001 75 11 5416 5420 10.1128/JVI.75.11.5416‑5420.2001 11333927
    [Google Scholar]
  23. Frieke Kuper C. Koornstra P.J. Hameleers D.M.H. Biewenga J. Spit B.J. Duijvestijn A.M. van Breda Vriesman P.J.C. Sminia T. The role of nasopharyngeal lymphoid tissue. Immunol. Today 1992 13 6 219 224 10.1016/0167‑5699(92)90158‑4 1627250
    [Google Scholar]
  24. Perry M. Whyte A. Immunology of the tonsils. Immunol. Today 1998 19 9 414 421 10.1016/S0167‑5699(98)01307‑3 9745205
    [Google Scholar]
  25. Bienenstock J. McDermott M.R. Bronchus‐ and nasal‐associated lymphoid tissues. Immunol. Rev. 2005 206 1 22 31 10.1111/j.0105‑2896.2005.00299.x 16048540
    [Google Scholar]
  26. Cesta M.F. Normal structure, function, and histology of mucosa-associated lymphoid tissue. Toxicol. Pathol. 2006 34 5 599 608 10.1080/01926230600865531 17067945
    [Google Scholar]
  27. Howie A.J. Scanning and transmission electron microscopy on the epithelium of human palatine tonsils. J. Pathol. 1980 130 2 91 98 10.1002/path.1711300205 7365575
    [Google Scholar]
  28. Jahnsen F.L. Gran E. Haye R. Brandtzaeg P. Human nasal mucosa contains antigen-presenting cells of strikingly different functional phenotypes. Am. J. Respir. Cell Mol. Biol. 2004 30 1 31 37 10.1165/rcmb.2002‑0230OC 12829449
    [Google Scholar]
  29. Debin A. Kravtzoff R. Santiago J.V. Cazales L. Sperandio S. Melber K. Janowicz Z. Betbeder D. Moynier M. Intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and CTL responses. Vaccine 2002 20 21-22 2752 2763 10.1016/S0264‑410X(02)00191‑3 12034102
    [Google Scholar]
  30. Price G.E. Soboleski M.R. Lo C.Y. Misplon J.A. Quirion M.R. Houser K.V. Pearce M.B. Pappas C. Tumpey T.M. Epstein S.L. Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1, H3N2 and H1N1 viruses. PLoS One 2010 5 10 e13162 10.1371/journal.pone.0013162 20976273
    [Google Scholar]
  31. Hemann E.A. Kang S.M. Legge K.L. Protective CD8 T cell-mediated immunity against influenza A virus infection following influenza virus-like particle vaccination. J. Immunol. 2013 191 5 2486 2494 10.4049/jimmunol.1300954 23885108
    [Google Scholar]
  32. Aguilar J.C. Lobaina Y. Muzio V. García D. Pentón E. Iglesias E. Pichardo D. Urquiza D. Rodríguez D. Silva D. Petrovsky N. Guillén G. Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen. Immunol. Cell Biol. 2004 82 5 539 546 10.1111/j.0818‑9641.2004.01278.x 15479440
    [Google Scholar]
  33. Rudin A. Johansson E.L. Bergquist C. Holmgren J. Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans. Infect. Immun. 1998 66 7 3390 3396 10.1128/IAI.66.7.3390‑3396.1998 9632610
    [Google Scholar]
  34. Kaetzel C.S. The polymeric immunoglobulin receptor: Bridging innate and adaptive immune responses at mucosal surfaces. Immunol. Rev. 2005 206 1 83 99 10.1111/j.0105‑2896.2005.00278.x 16048543
    [Google Scholar]
  35. Nizard M. Diniz M.O. Roussel H. Tran T. Ferreira L.C.S. Badoual C. Tartour E. Mucosal vaccines. Hum. Vaccin. Immunother. 2014 10 8 2175 2187 10.4161/hv.29269 25424921
    [Google Scholar]
  36. Sigmundsdottir H. Butcher E.C. Environmental cues, dendritic cells and the programming of tissue-selective lymphocyte trafficking. Nat. Immunol. 2008 9 9 981 987 10.1038/ni.f.208 18711435
    [Google Scholar]
  37. Mora J.R. Bono M.R. Manjunath N. Weninger W. Cavanagh L.L. Rosemblatt M. von Andrian U.H. Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells. Nature 2003 424 6944 88 93 10.1038/nature01726 12840763
    [Google Scholar]
  38. Ogra P.L. Karzon D.T. Poliovirus antibody response in serum and nasal secretions following intranasal inoculation with inactivated poliovaccine. J. Immunol. 1969 102 1 15 23 10.4049/jimmunol.102.1.15 4303877
    [Google Scholar]
  39. Johansson E.L. Wassén L. Holmgren J. Jertborn M. Rudin A. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans. Infect. Immun. 2001 69 12 7481 7486 10.1128/IAI.69.12.7481‑7486.2001 11705923
    [Google Scholar]
  40. Prakken B.J. van der Zee R. Anderton S.M. van Kooten P.J.S. Kuis W. van Eden W. Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis. Proc. Natl. Acad. Sci. USA 1997 94 7 3284 3289 10.1073/pnas.94.7.3284 9096385
    [Google Scholar]
  41. Hagiwara Y. McGhee J.R. Fujihashi K. Kobayashi R. Yoshino N. Kataoka K. Etani Y. Kweon M.N. Tamura S. Kurata T. Takeda Y. Kiyono H. Fujihashi K. Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissue. J. Immunol. 2003 170 4 1754 1762 10.4049/jimmunol.170.4.1754 12574339
    [Google Scholar]
  42. Fujihashi K. Kiyono H. Mucosal immunosenescence: New developments and vaccines to control infectious diseases. Trends Immunol. 2009 30 7 334 343 10.1016/j.it.2009.04.004 19540811
    [Google Scholar]
  43. Koga T. McGhee J.R. Kato H. Kato R. Kiyono H. Fujihashi K. Evidence for early aging in the mucosal immune system. J. Immunol. 2000 165 9 5352 5359 10.4049/jimmunol.165.9.5352 11046071
    [Google Scholar]
  44. Kobayashi A. Donaldson D.S. Erridge C. Kanaya T. Williams I.R. Ohno H. Mahajan A. Mabbott N.A. The functional maturation of M cells is dramatically reduced in the Peyer’s patches of aged mice. Mucosal Immunol. 2013 6 5 1027 1037 10.1038/mi.2012.141 23360902
    [Google Scholar]
  45. Lycke N. Recent progress in mucosal vaccine development: Potential and limitations. Nat. Rev. Immunol. 2012 12 8 592 605 10.1038/nri3251 22828912
    [Google Scholar]
  46. Gallichan W.S. Rosenthal K.L. Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization. J. Exp. Med. 1996 184 5 1879 1890 10.1084/jem.184.5.1879 8920875
    [Google Scholar]
  47. Belyakov I.M. Derby M.A. Ahlers J.D. Kelsall B.L. Earl P. Moss B. Strober W. Berzofsky J.A. Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge. Proc. Natl. Acad. Sci. USA 1998 95 4 1709 1714 10.1073/pnas.95.4.1709 9465081
    [Google Scholar]
  48. Karavasili C. Fatouros D.G. Smart materials: In situ gel-forming systems for nasal delivery. Drug Discov. Today 2016 21 1 157 166 10.1016/j.drudis.2015.10.016 26563428
    [Google Scholar]
  49. Amidi M. Romeijn S.G. Verhoef J.C. Junginger H.E. Bungener L. Huckriede A. Crommelin D.J.A. Jiskoot W. N-Trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination: Biological properties and immunogenicity in a mouse model. Vaccine 2007 25 1 144 153 10.1016/j.vaccine.2006.06.086 16973248
    [Google Scholar]
  50. Gilmore J.L. Yi X. Quan L. Kabanov A.V. Novel nanomaterials for clinical neuroscience. J. Neuroimmune Pharmacol. 2008 3 2 83 94 10.1007/s11481‑007‑9099‑6 18210200
    [Google Scholar]
  51. Fukuyama Y. Tokuhara D. Kataoka K. Gilbert R.S. McGhee J.R. Yuki Y. Kiyono H. Fujihashi K. Novel vaccine development strategies for inducing mucosal immunity. Expert Rev. Vaccines 2012 11 3 367 379 10.1586/erv.11.196 22380827
    [Google Scholar]
  52. Liang J.L. Tiwari T. Moro P. Messonnier N.E. Reingold A. Sawyer M. Clark T.A. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 2018 67 2 1 44 10.15585/mmwr.rr6702a1 29702631
    [Google Scholar]
  53. Buonagurio D.A. Bechert T.M. Yang C.F. Shutyak L. D’Arco G.A. Kazachkov Y. Wang H.P. Rojas E.A. O’Neill R.E. Spaete R.R. Coelingh K.L. Zamb T.J. Sidhu M.S. Udem S.A. Genetic stability of live, cold-adapted influenza virus components of the FluMist®/CAIV-T vaccine throughout the manufacturing process. Vaccine 2006 24 12 2151 2160 10.1016/j.vaccine.2005.11.007 16413951
    [Google Scholar]
  54. Ambrose C.S. Luke C. Coelingh K. Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza. Influenza Other Respir. Viruses 2008 2 6 193 202 10.1111/j.1750‑2659.2008.00056.x 19453395
    [Google Scholar]
  55. Fiore A.E. Uyeki T.M. Broder K. Finelli L. Euler G.L. Singleton J.A. Iskander J.K. Wortley P.M. Shay D.K. Bresee J.S. Cox N.J. Prevention and control of influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Recomm. Rep. 2010 59 RR-8 1 62 20689501
    [Google Scholar]
  56. Carter N.J. Curran M.P. Live attenuated influenza vaccine (FluMist®; Fluenz™): A review of its use in the prevention of seasonal influenza in children and adults. Drugs 2011 71 12 1591 1622 10.2165/11206860‑000000000‑00000 21861544
    [Google Scholar]
  57. Cape S. Safety and immunogenicity of dry powder measles vaccine administered by inhalation: A randomized controlled Phase I clinical trial. Vaccine 2014 32 50 6791 7 10.1016/j.vaccine.2014.09.071
    [Google Scholar]
  58. Hinkula J. Hagbom M. Wahren B. Schroder U. Safety and immunogenicity, after nasal application of HIV-1 DNA gagp37 plasmid vaccine in young mice. Vaccine 2008 26 40 5101 5106 10.1016/j.vaccine.2008.03.098 18482783
    [Google Scholar]
  59. Tiwari S. Verma S.K. Agrawal G.P. Vyas S.P. Viral protein complexed liposomes for intranasal delivery of hepatitis B surface antigen. Int. J. Pharm. 2011 413 1-2 211 219 10.1016/j.ijpharm.2011.04.029 21540094
    [Google Scholar]
  60. Derrick S.C. Kolibab K. Yang A. Morris S.L. Intranasal administration of Mycobacterium bovis BCG induces superior protection against aerosol infection with Mycobacterium tuberculosis in mice. Clin. Vaccine Immunol. 2014 21 10 1443 1451 10.1128/CVI.00394‑14 25143340
    [Google Scholar]
  61. Lorenzi J.C.C. Trombone A.P.F. Rocha C.D. Almeida L.P. Lousada R.L. Malardo T. Fontoura I.C. Rossetti R.A.M. Gembre A.F. Silva A.M. Silva C.L. Coelho-Castelo A.A.M. Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis. BMC Biotechnol. 2010 10 1 77 10.1186/1472‑6750‑10‑77 20961459
    [Google Scholar]
  62. Krishnan V. Andersen B.H. Shoemaker C. Sivko G.S. Tordoff K.P. Stark G.V. Zhang J. Feng T. Duchars M. Roberts M.S. Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model. Clin. Vaccine Immunol. 2015 22 4 430 439 10.1128/CVI.00690‑14 25673303
    [Google Scholar]
  63. Wu Y. Wei W. Zhou M. Wang Y. Wu J. Ma G. Su Z. Thermal-sensitive hydrogel as adjuvant-free vaccine delivery system for H5N1 intranasal immunization. Biomaterials 2012 33 7 2351 2360 10.1016/j.biomaterials.2011.11.068 22192540
    [Google Scholar]
  64. Fischer W.A. II King L.S. Lane A.P. Pekosz A. Restricted replication of the live attenuated influenza A virus vaccine during infection of primary differentiated human nasal epithelial cells. Vaccine 2015 33 36 4495 4504 10.1016/j.vaccine.2015.07.023 26196325
    [Google Scholar]
  65. Citron M.P. Patel M. Purcell M. Lin S.A. Rubins D.J. McQuade P. Callahan C. Gleason A. Petrescu I. Knapp W. Orekie C. Chamarthy S. Wen Z. Touch S. Pine M. Fontenot J. Douglas C. Liang X. Espeseth A.S. A novel method for strict intranasal delivery of non-replicating RSV vaccines in cotton rats and non-human primates. Vaccine 2018 36 20 2876 2885 10.1016/j.vaccine.2018.02.110 29599087
    [Google Scholar]
  66. Ball J.P. Springer M.J. Ni Y. Finger-Baker I. Martinez J. Hahn J. Suber J.F. DiMarco A.V. Talton J.D. Cobb R.R. Intranasal delivery of a bivalent norovirus vaccine formulated in an in situ gelling dry powder. PLoS One 2017 12 5 e0177310 10.1371/journal.pone.0177310 28545100
    [Google Scholar]
  67. Riddle M.S. Kaminski R.W. Williams C. Porter C. Baqar S. Kordis A. Gilliland T. Lapa J. Coughlin M. Soltis C. Jones E. Saunders J. Keiser P.B. Ranallo R.T. Gormley R. Nelson M. Turbyfill K.R. Tribble D. Oaks E.V. Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine. Vaccine 2011 29 40 7009 7019 10.1016/j.vaccine.2011.07.033 21787825
    [Google Scholar]
  68. Vajdy M. Singh M. Kazzaz J. Soenawan E. Ugozzoli M. Zhou F. Srivastava I. Bin Q. Barnett S. Donnelly J. Luciw P. Adamson L. Montefiori D. O’hagan D.T. Mucosal and systemic anti-HIV responses in rhesus macaques following combinations of intranasal and parenteral immunizations. AIDS Res. Hum. Retroviruses 2004 20 11 1269 1281 10.1089/aid.2004.20.1269 15588349
    [Google Scholar]
  69. Mäkitalo B. Lundholm P. Hinkula J. Nilsson C. Karlén K. Mörner A. Sutter G. Erfle V. Heeney J.L. Wahren B. Biberfeld G. Thorstensson R. Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen. J. Gen. Virol. 2004 85 8 2407 2419 10.1099/vir.0.79869‑0 15269383
    [Google Scholar]
  70. Barré-Sinoussi F. Chermann J.C. Rey F. Nugeyre M.T. Chamaret S. Gruest J. Dauguet C. Axler-Blin C. Vézinet-Brun F. Rouzioux C. Rozenbaum W. Montagnier L. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983 220 4599 868 871 10.1126/science.6189183 6189183
    [Google Scholar]
  71. Fuchs J.D. Sobieszczyk M.E. Hammer S.M. Buchbinder S.P. Lessons drawn from recent HIV vaccine efficacy trials. J. Acquir. Immune Defic. Syndr. 2010 55 Suppl 2 Suppl. 2 S128 S131 10.1097/QAI.0b013e3181fbca02 21406982
    [Google Scholar]
  72. Broliden K. Hinkula J. Devito C. Kiama P. Kimani J. Trabbatoni D. Bwayo J.J. Clerici M. Plummer F. Kaul R. Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG seronegative female sex workers. Immunol. Lett. 2001 79 1-2 29 36 10.1016/S0165‑2478(01)00263‑2 11595287
    [Google Scholar]
  73. Devito C. Hinkula J. Kaul R. Lopalco L. Bwayo J.J. Plummer F. Clerici M. Broliden K. Mucosal and plasma IgA from HIV-exposed seronegative individuals neutralize a primary HIV-1 isolate. AIDS 2000 14 13 1917 1920 10.1097/00002030‑200009080‑00006 10997395
    [Google Scholar]
  74. Leroux-Roels G. Maes C. Clement F. van Engelenburg F. van den Dobbelsteen M. Adler M. Amacker M. Lopalco L. Bomsel M. Chalifour A. Fleury S. Randomized Phase I: Safety, immunogenicity and mucosal antiviral activity in young healthy women vaccinated with HIV-1 gp41 P1 peptide on virosomes. PLoS One 2013 8 2 e55438 10.1371/journal.pone.0055438 23437055
    [Google Scholar]
  75. Bomsel M. Tudor D. Drillet A.S. Alfsen A. Ganor Y. Roger M.G. Mouz N. Amacker M. Chalifour A. Diomede L. Devillier G. Cong Z. Wei Q. Gao H. Qin C. Yang G.B. Zurbriggen R. Lopalco L. Fleury S. Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. Immunity 2011 34 2 269 280 10.1016/j.immuni.2011.01.015 21315623
    [Google Scholar]
  76. Moser C. Amacker M. Kammer A.R. Rasi S. Westerfeld N. Zurbriggen R. Influenza virosomes as a combined vaccine carrier and adjuvant system for prophylactic and therapeutic immunizations. Expert Rev. Vaccines 2007 6 5 711 721 10.1586/14760584.6.5.711 17931152
    [Google Scholar]
  77. Brekke K. Lind A. Holm-Hansen C. Haugen I.L. Sørensen B. Sommerfelt M. Kvale D. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial. PLoS One 2014 9 11 e112556 10.1371/journal.pone.0112556 25398137
    [Google Scholar]
  78. Shan L. Deng K. Shroff N.S. Durand C.M. Rabi S.A. Yang H.C. Zhang H. Margolick J.B. Blankson J.N. Siliciano R.F. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 2012 36 3 491 501 10.1016/j.immuni.2012.01.014 22406268
    [Google Scholar]
  79. Carcelain G. Autran B. Immune interventions in HIV infection. Immunol. Rev. 2013 254 1 355 371 10.1111/imr.12083 23772631
    [Google Scholar]
  80. Katlama C. Deeks S.G. Autran B. Martinez-Picado J. van Lunzen J. Rouzioux C. Miller M. Vella S. Schmitz J.E. Ahlers J. Richman D.D. Sekaly R.P. Barriers to a cure for HIV: New ways to target and eradicate HIV-1 reservoirs. Lancet 2013 381 9883 2109 2117 10.1016/S0140‑6736(13)60104‑X 23541541
    [Google Scholar]
  81. Åsjö B. Stavang H. Sørensen B. Baksaas I. Nyhus J. Langeland N. Phase I trial of a therapeutic HIV type 1 vaccine, Vacc-4x, in HIV type 1-infected individuals with or without antiretroviral therapy. AIDS Res. Hum. Retroviruses 2002 18 18 1357 1365 10.1089/088922202320935438 12487807
    [Google Scholar]
  82. Kiepiela P. Ngumbela K. Thobakgale C. Ramduth D. Honeyborne I. Moodley E. Reddy S. de Pierres C. Mncube Z. Mkhwanazi N. Bishop K. van der Stok M. Nair K. Khan N. Crawford H. Payne R. Leslie A. Prado J. Prendergast A. Frater J. McCarthy N. Brander C. Learn G.H. Nickle D. Rousseau C. Coovadia H. Mullins J.I. Heckerman D. Walker B.D. Goulder P. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat. Med. 2007 13 1 46 53 10.1038/nm1520 17173051
    [Google Scholar]
  83. Falkeborn T. Bråve A. Larsson M. Åkerlind B. Schröder U. Hinkula J. Endocine™, N3OA and N3OASq; three mucosal adjuvants that enhance the immune response to nasal influenza vaccination. PLoS One 2013 8 8 e70527 10.1371/journal.pone.0070527 23950951
    [Google Scholar]
  84. Lobaina Mato Y. Nasal route for vaccine and drug delivery: Features and current opportunities. Int. J. Pharm. 2019 572 118813 10.1016/j.ijpharm.2019.118813 31678521
    [Google Scholar]
  85. Iglesias E. García D. Carrazana Y. Aguilar J. Sánchez A. Gorobaya L. Blanco A. Anti-HIV-1 and anti-HBV immune responses in mice after parenteral and nasal co-administration of a multiantigenic formulation. Curr. HIV Res. 2008 6 5 452 460 10.2174/157016208785861186 18855656
    [Google Scholar]
  86. García-Díaz D. Rodríguez I. Santisteban Y. Márquez G. Terrero Y. Brown E. Iglesias E. Th2-Th1 shift with the multiantigenic formulation TERAVAC-HIV-1 in Balb/c mice. Immunol. Lett. 2013 149 1-2 77 84 10.1016/j.imlet.2012.11.007 23183092
    [Google Scholar]
  87. Macdonald N.E. Halperin B. Chaple E.B. Scott J. Kirk J.M. Kirk J.M. Infectious disease management: Lessons from cuba. Can. J. Infect. Dis. Med. Microbiol. 2006 17 4 217 220 10.1155/2006/351919 18382630
    [Google Scholar]
  88. Lobaina Y. Michel M.L. Chronic hepatitis B: Immunological profile and current therapeutic vaccines in clinical trials. Vaccine 2017 35 18 2308 2314 10.1016/j.vaccine.2017.03.049 28351734
    [Google Scholar]
  89. Lobaina M.Y. Aguilar Rubido JC, Guillen Nieto GE. HeberNasvac, a novel therapeutic vaccine for chronic hepatitis B patients. Almanac Clin Med. 2016 44 6 713 718 10.18786/2072‑0505‑2016‑44‑6‑713‑718
    [Google Scholar]
  90. Al Mahtab M. Akbar S.M.F. Aguilar J.C. Guillen G. Penton E. Tuero A. Yoshida O. Hiasa Y. Onji M. Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial). PLoS One 2018 13 8 e0201236 10.1371/journal.pone.0201236 30133478
    [Google Scholar]
  91. Lopez M Rodriguez EN Lobaina Y Musacchio A Falcon V Guillen G Characterization of the size distribution and aggregation of virus-like nanoparticles used as active ingredients of the HeberNasvac therapeutic vaccine against chronic hepatitis B*. Adv. Nat. Sci: Nanosci. Nanotechnol. 2017 8 2 025009 10.1088/2043‑6254/aa5e1d
    [Google Scholar]
  92. Betancourt A.A. Delgado C.A.G. Estévez Z.C. Martínez J.C. Ríos G.V. Aureoles-Roselló S.R.M. Zaldívar R.A. Guzmán M.A. Baile N.F. Reyes P.A.D. Ruano L.O. Fernández A.C. Lobaina-Matos Y. Fernández A.D. Madrazo A.I.J. Martínez M.I.A. Baños M.L. Alvarez N.P. Baldo M.D. Mestre R.E.S. Pérez M.V.P. Martínez M.E.P. Escobar D.A. Guanche M.J.C. Cáceres L.M. Betancourt R.S. Rando E.H. Nieto G.E.G. González V.L.M. Rubido J.C.A. Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens. Int. J. Infect. Dis. 2007 11 5 394 401 10.1016/j.ijid.2006.09.010 17257877
    [Google Scholar]
  93. WHO WHO vaccine-preventable diseases: 2010 global summary. 2010 Available From: https://iris.who.int/bitstream/handle/10665/70535/WHO_IVB_2010_eng.pdf
  94. Skerry C.M. Mahon B.P. A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model. Clin. Vaccine Immunol. 2011 18 2 187 193 10.1128/CVI.00371‑10 21147936
    [Google Scholar]
  95. Mielcarek N. Debrie A.S. Raze D. Bertout J. Rouanet C. Younes A.B. Creusy C. Engle J. Goldman W.E. Locht C. Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough. PLoS Pathog. 2006 2 7 e65 10.1371/journal.ppat.0020065 16839199
    [Google Scholar]
  96. Skerry C.M. Cassidy J.P. English K. Feunou-Feunou P. Locht C. Mahon B.P. A live attenuated Bordetella pertussis candidate vaccine does not cause disseminating infection in gamma interferon receptor knockout mice. Clin. Vaccine Immunol. 2009 16 9 1344 1351 10.1128/CVI.00082‑09 19625486
    [Google Scholar]
  97. Feunou P.F. Kammoun H. Debrie A.S. Mielcarek N. Locht C. Long-term immunity against pertussis induced by a single nasal administration of live attenuated B. pertussis BPZE1. Vaccine 2010 28 43 7047 7053 10.1016/j.vaccine.2010.08.017 20708998
    [Google Scholar]
  98. Thorstensson R. Trollfors B. Al-Tawil N. Jahnmatz M. Bergström J. Ljungman M. Törner A. Wehlin L. Van Broekhoven A. Bosman F. Debrie A.S. Mielcarek N. Locht C. A phase I clinical study of a live attenuated Bordetella pertussis vaccine--BPZE1; a single centre, double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally to healthy adult male volunteers. PLoS One 2014 9 1 e83449 10.1371/journal.pone.0083449 24421886
    [Google Scholar]
  99. Scott B.A. Yarchoan M. Jaffee E.M. Prophylactic vaccines for nonviral cancers. Annu. Rev. Cancer Biol. 2018 2 1 195 211 10.1146/annurev‑cancerbio‑030617‑050558
    [Google Scholar]
  100. Çuburu N. Graham B.S. Buck C.B. Kines R.C. Pang Y.Y.S. Day P.M. Lowy D.R. Schiller J.T. Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses. J. Clin. Invest. 2012 122 12 4606 4620 10.1172/JCI63287 23143305
    [Google Scholar]
  101. Sun Y.Y. Peng S. Han L. Qiu J. Song L. Tsai Y. Yang B. Roden R.B.S. Trimble C.L. Hung C.F. Wu T.C. Local HPV recombinant vaccinia boost following priming with an HPV DNA vaccine enhances local HPV-Specific CD8+ T-cell-mediated tumor control in the genital tract. Clin. Cancer Res. 2016 22 3 657 669 10.1158/1078‑0432.CCR‑15‑0234 26420854
    [Google Scholar]
  102. Sandoval F. Terme M. Nizard M. Badoual C. Bureau M.F. Freyburger L. Clement O. Marcheteau E. Gey A. Fraisse G. Bouguin C. Merillon N. Dransart E. Tran T. Quintin-Colonna F. Autret G. Thiebaud M. Suleman M. Riffault S. Wu T.C. Launay O. Danel C. Taieb J. Richardson J. Zitvogel L. Fridman W.H. Johannes L. Tartour E. Mucosal imprinting of vaccine-induced CD8⁺ T cells is crucial to inhibit the growth of mucosal tumors. Sci. Transl. Med. 2013 5 172 172ra20 10.1126/scitranslmed.3004888 23408053
    [Google Scholar]
  103. Decrausaz L. Pythoud C. Domingos-Pereira S. Derré L. Jichlinski P. Nardelli-Haefliger D. Intravaginal live attenuated Salmonella increases local antitumor vaccine-specific CD8 + T cells. OncoImmunology 2013 2 1 e22944 10.4161/onci.22944 23483225
    [Google Scholar]
  104. McMaster S.R. Wilson J.J. Wang H. Kohlmeier J.E. Airway-resident memory CD8 T cells provide antigen-specific protection against respiratory virus challenge through rapid IFN-gamma production. J. Immunol. 2015 195 1 203 209 10.4049/jimmunol.1402975 26026054
    [Google Scholar]
  105. Nizard M. Roussel H. Diniz M.O. Karaki S. Tran T. Voron T. Dransart E. Sandoval F. Riquet M. Rance B. Marcheteau E. Fabre E. Mandavit M. Terme M. Blanc C. Escudie J.B. Gibault L. Barthes F.L.P. Granier C. Ferreira L.C.S. Badoual C. Johannes L. Tartour E. Induction of resident memory T cells enhances the efficacy of cancer vaccine. Nat. Commun. 2017 8 1 15221 10.1038/ncomms15221 28537262
    [Google Scholar]
  106. Singh S. Yang G. Schluns K.S. Anthony S.M. Sastry K.J. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge. PLoS One 2014 9 3 e90001 10.1371/journal.pone.0090001 24599269
    [Google Scholar]
  107. Wakabayashi A. Nakagawa Y. Shimizu M. Moriya K. Nishiyama Y. Takahashi H. Suppression of an already established tumor growing through activated mucosal CTLs induced by oral administration of tumor antigen with cholera toxin. J. Immunol. 2008 180 6 4000 4010 10.4049/jimmunol.180.6.4000 18322209
    [Google Scholar]
  108. Domingos-Pereira S. Derré L. Warpelin-Decrausaz L. Haefliger J.A. Romero P. Jichlinski P. Nardelli-Haefliger D. Intravaginal and subcutaneous immunization induced vaccine specific CD8 T cells and tumor regression in the bladder. J. Urol. 2014 191 3 814 822 10.1016/j.juro.2013.08.009 23954582
    [Google Scholar]
  109. Ahmad S. Casey G. Cronin M. Rajendran S. Sweeney P. Tangney M. O’Sullivan G.C. Induction of effective antitumor response after mucosal bacterial vector mediated DNA vaccination with endogenous prostate cancer specific antigen. J. Urol. 2011 186 2 687 693 10.1016/j.juro.2011.03.139 21683415
    [Google Scholar]
  110. Kim-Schulze S. Kim H.S. Wainstein A. Kim D.W. Yang W.C. Moroziewicz D. Mong P.Y. Bereta M. Taback B. Wang Q. Kaufman H.L. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer. J. Immunol. 2008 181 11 8112 8119 10.4049/jimmunol.181.11.8112 19018004
    [Google Scholar]
  111. Finn O.J. Cancer Immunology. N. Engl. J. Med. 2008 358 25 2704 2715 10.1056/NEJMra072739 18565863
    [Google Scholar]
  112. Ahn B.N. Kim S.K. Shim C.K. Proliposomes as an intranasal dosage form for the sustained delivery of propranolol. J. Control. Release 1995 34 3 203 210 10.1016/0168‑3659(94)00114‑A
    [Google Scholar]
  113. Shyu W.C. Mayol R.F. Pfeffer M. Pittman K.A. Gammans R.E. Barbhaiya R.H. Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol. Biopharm. Drug Dispos. 1993 14 5 371 379 10.1002/bdd.2510140503 8218955
    [Google Scholar]
  114. Yang C. Gao H. Mitra A.K. Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir. J. Pharm. Sci. 2001 90 5 617 624 10.1002/1520‑6017(200105)90:5<617::AID‑JPS1018>3.0.CO;2‑5 11288106
    [Google Scholar]
  115. Nagpal K. Singh S.K. Mishra D.N. Chitosan nanoparticles: A promising system in novel drug delivery. Chem. Pharm. Bull. (Tokyo) 2010 58 11 1423 1430 10.1248/cpb.58.1423 21048331
    [Google Scholar]
  116. Vyas T.K. Babbar A.K. Sharma R.K. Misra A. Intranasal mucoadhesive microemulsions of zolmitriptan: Preliminary studies on brain-targeting. J. Drug Target. 2005 13 5 317 324 10.1080/10611860500246217 16199375
    [Google Scholar]
  117. Ozsoy Y. Gungor S. Cevher E. Nasal delivery of high molecular weight drugs. Molecules 2009 14 9 3754 3779 10.3390/molecules14093754 19783956
    [Google Scholar]
  118. Lochhead J.J. Thorne R.G. Fisher A.N. Hinchcliffe M. Norbury H. Jabbal-Gill I. Intranasal delivery of biologics to the central nervous system. Adv. Drug Deliv. Rev. 2012 64 7 614 628 10.1016/j.addr.2011.11.002 22119441
    [Google Scholar]
  119. de Lange E.C.M. The mastermind approach to CNS drug therapy: Translational prediction of human brain distribution, target site kinetics, and therapeutic effects. Fluids Barriers CNS 2013 10 1 12 10.1186/2045‑8118‑10‑12 23432852
    [Google Scholar]
  120. Merkus F.W.H.M. van den Berg M.P. Can nasal drug delivery bypass the blood-brain barrier?: Questioning the direct transport theory. Drugs R D. 2007 8 3 133 144 10.2165/00126839‑200708030‑00001 17472409
    [Google Scholar]
  121. Djupesland P.G. Messina J.C. Mahmoud R.A. The nasal approach to delivering treatment for brain diseases: An anatomic, physiologic, and delivery technology overview. Ther. Deliv. 2014 5 6 709 733 10.4155/tde.14.41 25090283
    [Google Scholar]
  122. Sjölinder H. Jonsson A.B. Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges. PLoS One 2010 5 11 e14034 10.1371/journal.pone.0014034 21124975
    [Google Scholar]
  123. Dando S.J. Mackay-Sim A. Norton R. Currie B.J. St John J.A. Ekberg J.A. Batzloff M. Ulett G.C. Beacham I.R. Pathogens penetrating the central nervous system: Infection pathways and the cellular and molecular mechanisms of invasion. Clin. Microbiol. Rev. 2014 27 4 691 726 10.1128/CMR.00118‑13 25278572
    [Google Scholar]
  124. Pardridge W.M. Drug transport across the blood-brain barrier. J. Cereb. Blood Flow Metab. 2012 32 11 1959 1972 10.1038/jcbfm.2012.126 22929442
    [Google Scholar]
  125. Freiherr J. Hallschmid M. Frey W.H. II Brünner Y.F. Chapman C.D. Hölscher C. Craft S. De Felice F.G. Benedict C. Intranasal insulin as a treatment for Alzheimer’s disease: A review of basic research and clinical evidence. CNS Drugs 2013 27 7 505 514 10.1007/s40263‑013‑0076‑8 23719722
    [Google Scholar]
  126. Graustella A.J. MacLeod C. A critical review of the influence of oxytocin nasal spray on social cognition in humans: Evidence and future directions. Horm. Behav. 2012 61 3 410 418 10.1016/j.yhbeh.2012.01.002 22265852
    [Google Scholar]
  127. Born J. Lange T. Kern W. McGregor G.P. Bickel U. Fehm H.L. Sniffing neuropeptides: A transnasal approach to the human brain. Nat. Neurosci. 2002 5 6 514 516 10.1038/nn0602‑849 11992114
    [Google Scholar]
  128. Danielyan L. Schäfer R. von Ameln-Mayerhofer A. Buadze M. Geisler J. Klopfer T. Burkhardt U. Proksch B. Verleysdonk S. Ayturan M. Buniatian G.H. Gleiter C.H. Frey W.H. II Intranasal delivery of cells to the brain. Eur. J. Cell Biol. 2009 88 6 315 324 10.1016/j.ejcb.2009.02.001 19324456
    [Google Scholar]
  129. Danielyan L. Schäfer R. von Ameln-Mayerhofer A. Bernhard F. Verleysdonk S. Buadze M. Lourhmati A. Klopfer T. Schaumann F. Schmid B. Koehle C. Proksch B. Weissert R. Reichardt H.M. van den Brandt J. Buniatian G.H. Schwab M. Gleiter C.H. Frey W.H. II Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Rejuvenation Res. 2011 14 1 3 16 10.1089/rej.2010.1130 21291297
    [Google Scholar]
  130. Thorne R.G. Pronk G.J. Padmanabhan V. Frey W.H. II Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 2004 127 2 481 496 10.1016/j.neuroscience.2004.05.029 15262337
    [Google Scholar]
  131. Deadwyler S.A. Porrino L. Siegel J.M. Hampson R.E. Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates. J. Neurosci. 2007 27 52 14239 14247 10.1523/JNEUROSCI.3878‑07.2007 18160631
    [Google Scholar]
  132. Dhama K. Dhawan M. Tiwari R. Emran T.B. Mitra S. Rabaan A.A. Alhumaid S. Alawi Z.A. Al Mutair A. COVID-19 intranasal vaccines: Current progress, advantages, prospects, and challenges. Hum. Vaccin. Immunother. 2022 18 5 2045853 10.1080/21645515.2022.2045853 35258416
    [Google Scholar]
  133. Bleier B.S. Ramanathan M. Jr Lane A.P. COVID-19 vaccines may not prevent nasal SARS-CoV-2 infection and asymptomatic transmission. Otolaryngol. Head Neck Surg. 2021 164 2 305 307 10.1177/0194599820982633 33320052
    [Google Scholar]
  134. McLenon J. Rogers M.A.M. The fear of needles: A systematic review and meta‐analysis. J. Adv. Nurs. 2019 75 1 30 42 10.1111/jan.13818 30109720
    [Google Scholar]
  135. Olive C. Sun H.K. Ho M.F. Dyer J. Horváth A. Toth I. Good M.F. Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein. J. Infect. Dis. 2006 194 3 316 324 10.1086/505580 16826479
    [Google Scholar]
  136. Peek L.J. Middaugh C.R. Berkland C. Nanotechnology in vaccine delivery. Adv. Drug Deliv. Rev. 2008 60 8 915 928 10.1016/j.addr.2007.05.017 18325628
    [Google Scholar]
  137. Butler S.E. Crowley A.R. Natarajan H. Xu S. Weiner J.A. Bobak C.A. Mattox D.E. Lee J. Wieland-Alter W. Connor R.I. Wright P.F. Ackerman M.E. Features and functions of systemic and mucosal humoral immunity among SARS-CoV-2 convalescent individuals, medRxiv. Front. Immunol. 2021 11 618685 10.3389/fimmu.2020.618685 33584712
    [Google Scholar]
  138. Yusuf H. Kett V. Current prospects and future challenges for nasal vaccine delivery. Hum. Vaccin. Immunother. 2017 13 1 34 45 10.1080/21645515.2016.1239668 27936348
    [Google Scholar]
  139. van de Pavert S.A. Mebius R.E. New insights into the development of lymphoid tissues. Nat. Rev. Immunol. 2010 10 9 664 674 10.1038/nri2832 20706277
    [Google Scholar]
  140. Kagnoff M.F. Eckmann L. Epithelial cells as sensors for microbial infection. J. Clin. Invest. 1997 100 1 6 10 10.1172/JCI119522 9202050
    [Google Scholar]
  141. Hargreaves D.C. Medzhitov R. Innate sensors of microbial infection. J. Clin. Immunol. 2005 25 6 503 510 10.1007/s10875‑005‑8065‑4 16380814
    [Google Scholar]
  142. Illum L. Nanoparticulate systems for nasal delivery of drugs: A real improvement over simple systems? J. Pharm. Sci. 2007 96 3 473 483 10.1002/jps.20718 17117404
    [Google Scholar]
  143. Burgdorf S. Kautz A. Böhnert V. Knolle P.A. Kurts C. Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science 2007 316 5824 612 616 10.1126/science.1137971 17463291
    [Google Scholar]
  144. Sansonetti P.J. Di Santo J.P. Debugging how bacteria manipulate the immune response. Immunity 2007 26 2 149 161 10.1016/j.immuni.2007.02.004 17307704
    [Google Scholar]
  145. Skwarczynski M. Toth I. Non-invasive mucosal vaccine delivery: Advantages, challenges and the future. Expert Opin. Drug Deliv. 2020 17 4 435 437 10.1080/17425247.2020.1731468 32059625
    [Google Scholar]
  146. Lijek R.S. Luque S.L. Liu Q. Parker D. Bae T. Weiser J.N. Protection from the acquisition of Staphylococcus aureus nasal carriage by cross-reactive antibody to a pneumococcal dehydrogenase. Proc. Natl. Acad. Sci. USA 2012 109 34 13823 13828 10.1073/pnas.1208075109 22869727
    [Google Scholar]
  147. Pashine A. Valiante N.M. Ulmer J.B. Targeting the innate immune response with improved vaccine adjuvants. Nat. Med. 2005 11 S4 Suppl. S63 S68 10.1038/nm1210 15812492
    [Google Scholar]
  148. Linehan J.L. Dileepan T. Kashem S.W. Kaplan D.H. Cleary P. Jenkins M.K. Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b + dendritic cells. Proc. Natl. Acad. Sci. USA 2015 112 41 12782 12787 10.1073/pnas.1513532112 26417101
    [Google Scholar]
  149. Wang S. Liu H. Zhang X. Qian F. Intranasal and oral vaccination with protein-based antigens: Advantages, challenges and formulation strategies. Protein Cell 2015 6 7 480 503 10.1007/s13238‑015‑0164‑2 25944045
    [Google Scholar]
  150. Jabbal-Gill I. Nasal vaccine innovation. J. Drug Target. 2010 18 10 771 786 10.3109/1061186X.2010.523790 21047271
    [Google Scholar]
  151. Afkhami S. Yao Y. Xing Z. Methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens. Mol. Ther. Methods Clin. Dev. 2016 3 16030 10.1038/mtm.2016.30 27162933
    [Google Scholar]
  152. Malik J.A. Mulla A.H. Farooqi T. Pottoo F.H. Anwar S. Rengasamy K.R.R. Targets and strategies for vaccine development against SARS-CoV-2. Biomed. Pharmacother. 2021 137 111254 10.1016/j.biopha.2021.111254 33550049
    [Google Scholar]
  153. Guo J. Mondal M. Zhou D. Development of novel vaccine vectors: Chimpanzee adenoviral vectors. Hum. Vaccin. Immunother. 2018 14 7 1679 1685 10.1080/21645515.2017.1419108 29300685
    [Google Scholar]
  154. Chavda V.P. Vora L.K. Pandya A.K. Patravale V.B. Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management. Drug Discov. Today 2021 26 11 2619 2636 10.1016/j.drudis.2021.07.021 34332100
    [Google Scholar]
  155. van Doremalen N. Purushotham J.N. Schulz J.E. Holbrook M.G. Bushmaker T. Carmody A. Port J.R. Yinda C.K. Okumura A. Saturday G. Amanat F. Krammer F. Hanley P.W. Smith B.J. Lovaglio J. Anzick S.L. Barbian K. Martens C. Gilbert S.C. Lambe T. Munster V.J. 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 10.1126/scitranslmed.abh0755 34315826
    [Google Scholar]
  156. Hassan A.O. Kafai N.M. Dmitriev I.P. Fox J.M. Smith B.K. Harvey I.B. Chen R.E. Winkler E.S. Wessel A.W. Case J.B. Kashentseva E. McCune B.T. Bailey A.L. Zhao H. VanBlargan L.A. Dai Y.N. Ma M. Adams L.J. Shrihari S. Danis J.E. Gralinski L.E. Hou Y.J. Schäfer A. Kim A.S. Keeler S.P. Weiskopf D. Baric R.S. Holtzman M.J. Fremont D.H. Curiel D.T. Diamond M.S. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell 2020 183 1 169 184.e13 10.1016/j.cell.2020.08.026 32931734
    [Google Scholar]
  157. Singh C. Verma S. Reddy P. Diamond M.S. Curiel D.T. Patel C. Jain M.K. Redkar S.V. Bhate A.S. Gundappa V. Konatham R. Toppo L. Joshi A.C. Kushwaha J.S. Singh A.P. Bawankule S. Ella R. Prasad S. Ganneru B. Chiteti S.R. Kataram S. Vadrevu K.M. Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin®). NPJ Vaccines 2023 8 1 125 10.1038/s41541‑023‑00717‑8 37596281
    [Google Scholar]
  158. CanSino Biologics Inc Phase I/​II Clinical Trial of Recombinant Novel Coronavirus (COVID-19) Vaccine (Adenovirus Type 5 Vector) for Inhalation. 2023 Available From: https://clinicaltrials.gov/ct2/show/NCT04840992
  159. Anhui Zhifei Longcom Biologic Pharmacy Co A Phase III Clinical Trial to Determine the Safety and Efficacy of ZF2001 for Prevention of COVID-19. 2022 Available From: https://clinicaltrials.gov/ct2/show/NCT04646590
  160. Altimmune Inc NasoVAX in Patients With Early Coronavirus Infectious Disease 2019 (COVID-19). 2022 Available From: https://clinicaltrials.gov/ct2/show/NCT04442230
  161. King R.G. Silva-Sanchez A. Peel J.N. Botta D. Dickson A.M. Pinto A.K. Meza-Perez S. Allie S.R. Schultz M.D. Liu M. Bradley J.E. Qiu S. Yang G. Zhou F. Zumaquero E. Simpler T.S. Mousseau B. Killian J.T. Jr Dean B. Shang Q. Tipper J.L. Risley C.A. Harrod K.S. Feng T. Lee Y. Shiberu B. Krishnan V. Peguillet I. Zhang J. Green T.J. Randall T.D. Suschak J.J. Georges B. Brien J.D. Lund F.E. Roberts M.S. Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge. Vaccines (Basel) 2021 9 8 881 976 10.3390/vaccines9080881 34452006
    [Google Scholar]
  162. FluGen Inc. Focused on efficacy-M2SR:40th Annual J.P. Morgan Healthcare Conference. 2022 Available From: https://kvgo.com/baird-2021-global-healthcare-conference/flugen-inc-sept
  163. Sarawar S. Hatta Y. Watanabe S. Dias P. Neumann G. Kawaoka Y. Bilsel P. M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice. Vaccine 2016 34 42 5090 5098 10.1016/j.vaccine.2016.08.061 27595896
    [Google Scholar]
  164. Rubin R. COVID-19 Vaccine Nasal Spray. JAMA 2021 326 12 1138 1146 10.1001/jama.2021.14996 34581751
    [Google Scholar]
  165. Wang Y. Xing M. Zhou D. Coronavirus disease-19 vaccine development utilizing promising technology. Curr. Opin. HIV AIDS 2020 15 6 351 358 10.1097/COH.0000000000000648 32969973
    [Google Scholar]
  166. Ruckwardt T.J. Morabito K.M. Phung E. Crank M.C. Costner P.J. Holman L.A. Chang L.A. Hickman S.P. Berkowitz N.M. Gordon I.J. Yamshchikov G.V. Gaudinski M.R. Lin B. Bailer R. Chen M. Ortega-Villa A.M. Nguyen T. Kumar A. Schwartz R.M. Kueltzo L.A. Stein J.A. Carlton K. Gall J.G. Nason M.C. Mascola J.R. Chen G. Graham B.S. Arthur A. Cunningham J. Eshun A. Larkin B. Mendoza F. Novik L. Saunders J. Wang X. Whalen W. Carter C. Hendel C.S. Plummer S. Ola A. Widge A. Burgos Florez M.C. Le L. Pittman I. Rothwell R.S.S. Trofymenko O. Vasilenko O. Apte P. Hicks R. Cartagena C.T. Williams P. Requilman L.S. Tran C. Bai S. Carey E. Chamberlain A.L. Chang Y. Chen M. Chen P. Cooper J. Fridley C. Ghosh M. Gollapudi D. Holland-Linn J. Horwitz J. Hussain A. Ivleva V. Kaltovich F. Leach K. Lee C. Liu A. Liu X. Manceva S. Menon A. Nagy A. O’Connell S. Ragunathan R. Walters J. Zhao Z. Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: A phase 1, randomised, open-label, dose-escalation clinical trial. Lancet Respir. Med. 2021 9 10 1111 1120 10.1016/S2213‑2600(21)00098‑9 33864736
    [Google Scholar]
  167. Tandon R. Joshi A. Current Status of Intranasal COVID-19 Vaccine, its Usage and Efficacy: A Narrative Review. J. Clin. Diagn. Res. 2023 17 5 LE07 LE10 10.7860/JCDR/2023/63348.17943
    [Google Scholar]
  168. Groen J. Intravacc. 2021 Available From: http://www.intravacc.nl/news/intravacc-announces-positive-preclinical-data-intranasal-sars-cov-2-candidate-vaccine/
  169. Koshy S.T. Cheung A.S. Gu L. Graveline A.R. Mooney D.J. Liposomal delivery enhances immune activation by STING agonists for cancer immunotherapy. Adv. Biosyst. 2017 1 1-2 1600013 10.1002/adbi.201600013 30258983
    [Google Scholar]
  170. Meyer M.J. AuraVax Therapeutics licences intranasal vaccine adjuvant technology from Massachusetts General Hospital. 2021 Available From: http://www.oindpnews.com/2021/01/auravax therapeutics-licences-intranasal-vaccine-adjuvant-technology-from massachusetts-general-hospital/
  171. Mitchell J.P. Berlinski A. Canisius S. Cipolla D. Dolovich M.B. Gonda I. Hochhaus G. Kadrichu N. Lyapustina S. Mansour H.M. Darquenne C. Clark A.R. Newhouse M. Ehrmann S. Humphries R. Boushey H. Urgent appeal from International Society for Aerosols in Medicine (ISAM) during COVID-19: Clinical decision makers and governmental agencies should consider the inhaled route of administration: A statement from the ISAM Regulatory and Standardization Issues Networking Group. J. Aerosol Med. Pulm. Drug Deliv. 2020 33 4 235 238 10.1089/jamp.2020.1622 32589076
    [Google Scholar]
  172. Parkins K. SaNOtize’s ‘revolutionary’ Covid-19 nasal spray bolstered by Phase II trial data. Available From: https://www.clinicaltrialsarena.com/news/sanotize-nasal-spray-reduces-covid-19-viral-load-uk-clinical-trail/
  173. Weinberger B. Laskin D.L. Heck D.E. Laskin J.D. The toxicology of inhaled nitric oxide. Toxicol. Sci. 2001 59 1 5 16 10.1093/toxsci/59.1.5 11134540
    [Google Scholar]
  174. Åkerström S. Gunalan V. Keng C.T. Tan Y.J. Mirazimi A. Dual effect of nitric oxide on SARS-CoV replication: Viral RNA production and palmitoylation of the S protein are affected. Virology 2009 395 1 1 9 10.1016/j.virol.2009.09.007 19800091
    [Google Scholar]
  175. Businesswire UK Clinical Trial Confirms SaNOtize’s Breakthrough Treatment for COVID-19. 2021 Available From: https://www.businesswire.com/news/home/20210315005197/en/UK-Clinical-Trial-Confirms-SaNOtize%E2%80%99s-Breakthrough-Treatment-for-COVID-19
  176. Sanotize Research and Development Corp. Nitric Oxide Releasing Solutions to Prevent and Treat Mild/​Moderate COVID-19 Infection (NOCOVID). 2021 Available From: https://clinicaltrials.gov/ct2/show/NCT04337918
  177. Murugan C. Ramamoorthy S. Kuppuswamy G. Murugan R.K. Sivalingam Y. Sundaramurthy A. COVID-19: A review of newly formed viral clades, pathophysiology, therapeutic strategies and current vaccination tasks. Int. J. Biol. Macromol. 2021 193 Pt B 1165 1200 10.1016/j.ijbiomac.2021.10.144 34710479
    [Google Scholar]
  178. Monsalve-Naharro J.A. Domingo-Chiva E. García Castillo S. Cuesta-Montero P. Jiménez-Vizuete J.M. Inhaled nitric oxide in adult patients with acute respiratory distress syndrome. Farm. Hosp. 2017 41 2 292 312 10.7399/fh.2017.41.2.10533 28236803
    [Google Scholar]
  179. VeroBiotech Home Use of GENOSYL® Delivery System (DS) to Administer GENOSYL® (nitric oxide) gas for Inhalation for the Treatment of Pulmonary Hypertension Complicated by COVID-19 Infection Published in American Journal of Respiratory and Critical Care Medicine. 2020 Available From: www.vero–biotech.com
  180. Tzotzos S.J. Fischer B. Fischer H. Zeitlinger M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: A global literature survey. Crit. Care 2020 24 1 516 10.1186/s13054‑020‑03240‑7 32825837
    [Google Scholar]
  181. Shmuel K. Dalia M. Tair L. Yaakov N. Low pH Hypromellose (Taffix) nasal powder spray could reduce SARS-CoV-2 infection rate post mass-gathering event at a highly endemic community: An observational prospective open label user survey. Expert Rev. Anti Infect. Ther. 2021 19 10 1325 1330 10.1080/14787210.2021.1908127 33759682
    [Google Scholar]
  182. Moakes R.J.A. Davies S.P. Stamataki Z. Grover L.M. Formulation of a composite nasal spray enabling enhanced surface coverage and prophylaxis of SARS-COV-2. BioRxiv 2020 10.1101/2020.11.18.388645
    [Google Scholar]
  183. Buller F. Neurimmune and Ethris sign collaboration agreement to rapidly develop inhaled mRNA-based antibody therapy for the treatment of Covid-19. 2020 Available From: http://www.neurimmune.com/news/neurimmune-and-ethris-sign
  184. Windtree Therapeutics Trial to Assess the Safety and Tolerability of Lucinactant for Inhalation in Premature Neonates. 2019 Available From: https://clinicaltrials.gov/ct2/show/NCT02074059
  185. Duvignaud A. Lhomme E. Onaisi R. Sitta R. Gelley A. Chastang J. Piroth L. Binquet C. Dupouy J. Makinson A. Lefèvre B. Naccache J.M. Roussillon C. Landman R. Wallet C. Karcher S. Journot V. Nguyen D. Pistone T. Bouchet S. Lafon M.E. Molimard M. Thiébaut R. de Lamballerie X. Joseph J.P. Richert L. Saint-Lary O. Djabarouti S. Wittkop L. Anglaret X. Malvy D. Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: A randomised controlled trial (COVERAGE). Clin. Microbiol. Infect. 2022 28 7 1010 1016 10.1016/j.cmi.2022.02.031 35304280
    [Google Scholar]
  186. Chavda V.P. Baviskar K.P. Vaghela D.A. Raut S.S. Bedse A.P. Nasal sprays for treating COVID-19: A scientific note. Pharmacol. Rep. 2023 75 2 249 265 10.1007/s43440‑023‑00463‑7 36848033
    [Google Scholar]
  187. Temerozo J.R. Sacramenta Q. Fintelman-Rodriques N. The neuropeptides VIP and PACAP inhibit SARS-CoV-2 replication in monocytes and lung epithelial cells, decrease the production of proinflammatory cytokines, and VIP levels are associated with survival in severe Covid-19 patients. J. Leukoc. Biol. 2022 111 5 1107 1121 10.1002/JLB.5COVA1121‑626R 35322471
    [Google Scholar]
  188. Rösler B. Herold S. Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia—a new therapeutic strategy? Mol. Cell Pediatr. 2016 3 1 29 42 10.1186/s40348‑016‑0055‑5 27480877
    [Google Scholar]
  189. Liebowitz M.R. Salman E. Nicolini H. Rosenthal N. Hanover R. Monti L. Effect of an acute intranasal aerosol dose of PH94B on social and performance anxiety in women with social anxiety disorder. Am. J. Psychiatry 2014 171 6 675 682 10.1176/appi.ajp.2014.12101342 24700254
    [Google Scholar]
  190. Lacroix M. Rousseau F. Guilhot F. Malinge P. Magistrelli G. Herren S. Jones S.A. Jones G.W. Scheller J. Lissilaa R. Kosco-Vilbois M. Johnson Z. Buatois V. Ferlin W. Novel insights into interleukin 6 (IL-6) cis- and trans-signaling pathways by differentially manipulating the assembly of the IL-6 signaling complex. J. Biol. Chem. 2015 290 45 26943 26953 10.1074/jbc.M115.682138 26363066
    [Google Scholar]
  191. Ampio Pharmaceuticals. Inc. Study of Ampion for the treatment of Adult COVID-19 patients requiring oxygen supplementation. 2021 Available From: https://clinicaltrials.gov/ct2/show/NCT04456452
  192. Monk P.D. Marsden R.J. Tear V.J. Brookes J. Batten T.N. Mankowski M. Gabbay F.J. Davies D.E. Holgate S.T. Ho L.P. Clark T. Djukanovic R. Wilkinson T.M.A. Crooks M.G. Dosanjh D.P.S. Siddiqui S. Rahman N.M. Smith J.A. Horsley A. Harrison T.W. Saralaya D. McGarvey L. Watson A. Foster E. Fleet A. Singh D. Hemmings S. Aitken S. Dudley S. Beegan R. Thompson A. Rodrigues P.M.B. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir. Med. 2021 9 2 196 206 10.1016/S2213‑2600(20)30511‑7 33189161
    [Google Scholar]
  193. Pfizer Long-term Safety Study of BHV-3500 (Zavegepant*) for the Acute Treatment of Migraine. 2023 Available From: https://clinicaltrials.gov/study/NCT04408794
  194. Mutsch M. Zhou W. Rhodes P. Bopp M. Chen R.T. Linder T. Spyr C. Steffen R. 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 10.1056/NEJMoa030595 14985487
    [Google Scholar]
  195. Izurieta H.S. Haber P. Wise R.P. Iskander J. Pratt D. Mink C. Chang S. Braun M.M. Ball R. Adverse events reported following live, cold-adapted, intranasal influenza vaccine. JAMA 2005 294 21 2720 2725 10.1001/jama.294.21.2720 16333007
    [Google Scholar]
  196. Stowe J. Andrews N. Wise L. Miller E. Bell’s palsy and parenteral inactivated influenza vaccine. Hum. Vaccin. 2006 2 3 110 112 10.4161/hv.2790 17012908
    [Google Scholar]
  197. Rowhani-Rahbar A. Klein N.P. Lewis N. Fireman B. Ray P. Rasgon B. Black S. Klein J.O. Baxter R. Immunization and Bell’s palsy in children: A case-centered analysis. Am. J. Epidemiol. 2012 175 9 878 885 10.1093/aje/kws011 22411861
    [Google Scholar]
  198. Souvik Chattopadhyay Sourav Chakraborty Sumon Sheel Dipan Roy Souvik Biswas Mrinmoy Nag Sanjit Mandal Amartya Sen Nasal route: A breakthrough for drug delivery. J. Pharm. Negat. Results 2022 13 9 315 334 10.47750/pnr.2022.13.S09.038
    [Google Scholar]
  199. Chattopadhyay S. Das S. Sarma K.N. NOSE-TO-brain drug delivery: An update to the alternative path to successful targeted anti-migraine drugs. International Journal of Applied Pharmaceutics 2021 13 2 67 75 10.22159/ijap.2021v13i2.40404
    [Google Scholar]
/content/journals/covid/10.2174/0126667975293193240826093456
Loading
/content/journals/covid/10.2174/0126667975293193240826093456
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: mucosal administration ; nasal route ; vaccines ; nasal delivery ; Drug delivery
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test