Intranasal Immunization with DNA Vaccine HA-CCL19/Polyethylenimine/Chitosan Composite Provides Immune Protection Against H7N9 Infection.

Yuqing Xiang, Hongbo Zhang, Youcai An, Ze Chen
Author Information
  1. Yuqing Xiang: Department of Basic Research, Ab & B Bio-Tech Co., Ltd. JS, Taizhou 225300, China.
  2. Hongbo Zhang: Department of Basic Research, Ab & B Bio-Tech Co., Ltd. JS, Taizhou 225300, China.
  3. Youcai An: Department of Basic Research, Ab & B Bio-Tech Co., Ltd. JS, Taizhou 225300, China.
  4. Ze Chen: Department of Basic Research, Ab & B Bio-Tech Co., Ltd. JS, Taizhou 225300, China.

Abstract

BACKGROUND/OBJECTIVES: The H7N9 avian influenza virus (AIV) constitutes a novel subtype of influenza virus that has emerged within the past decade. Empirical studies have demonstrated that H7N9 AIV holds the potential to trigger a human pandemic. Vaccines constitute the sole armament available to humanity in combating influenza epidemics. DNA vaccines present numerous merits; however, substantial conundrums persist regarding how to augment their immunogenicity and implement their delivery through mucosal immunization.
METHODS: In this study; BALB/c mice were utilized as a model to investigate the effect of CCL19 as a molecular adjuvant and to determine the immune response elicited by polyethylene imine (PEI) and chitosan (CS) as adjuvants during the delivery of a DNA vaccine through the nasal mucosal route.
RESULTS: Our results revealed that the CCL19 molecular adjuvant exerts a substantial immunomodulatory enhancement effect on the H7N9-HA DNA vaccine, inducing more pronounced cellular and humoral immunity. Additionally, our results indicated that the composite formed by the HA-CCL19 DNA in combination with PEI and CS effectively activates local mucosal immunity as well as systemic humoral and cellular immunity, offering 100% protection against lethal doses of homologous virus challenges.
CONCLUSIONS: CCL19 conspicuously augments the immunogenicity of the influenza virus HA DNA and conserves the integrity of the vaccine antigen. Simultaneously, CS and PEI proficiently facilitate the mucosal delivery of DNA, thereby eliciting mucosal immunity related to DNA vaccines. This study investigated the feasibility of utilizing nasal mucosa for DNA vaccine immunization, which holds significant implications for the advancement and application of DNA vaccines in public health.

Keywords

References

  1. Sci Immunol. 2018 Jul 6;3(25): [PMID: 29980618]
  2. Arch Virol. 2011 Mar;156(3):387-95 [PMID: 21110049]
  3. Expert Rev Vaccines. 2019 Aug;18(8):859-865 [PMID: 31318303]
  4. Cytokine. 2021 Dec;148:155703 [PMID: 34555604]
  5. Front Immunol. 2018 Jul 09;9:1568 [PMID: 30038621]
  6. Vaccines (Basel). 2021 Sep 17;9(9): [PMID: 34579269]
  7. Vaccines (Basel). 2024 Jun 08;12(6): [PMID: 38932372]
  8. Adv Drug Deliv Rev. 2001 Sep 23;51(1-3):81-96 [PMID: 11516781]
  9. Nat Biotechnol. 2012 Sep;30(9):883-8 [PMID: 22922673]
  10. J Control Release. 2012 Jan 10;157(1):86-93 [PMID: 21907252]
  11. Biomed Res Int. 2020 Jan 3;2020:2032057 [PMID: 31998782]
  12. Hum Vaccin Immunother. 2017 Dec 2;13(12):2837-2848 [PMID: 28604157]
  13. Front Immunol. 2021 Oct 08;12:747032 [PMID: 34691056]
  14. Cytokine Growth Factor Rev. 2013 Jun;24(3):269-83 [PMID: 23587803]
  15. J Virol. 2010 Dec;84(24):12703-12 [PMID: 20881038]
  16. Gene Ther. 2011 Nov;18(11):1070-7 [PMID: 21544096]
  17. Methods Mol Biol. 2020;2123:83-92 [PMID: 32170682]
  18. Int Immunol. 2017 Dec 18;29(10):471-478 [PMID: 29186424]
  19. Int J Biol Macromol. 2024 Oct;277(Pt 4):134531 [PMID: 39116977]
  20. Influenza Other Respir Viruses. 2008 Mar;2(2):41-51 [PMID: 19453471]
  21. Int J Nanomedicine. 2017 Jul 31;12:5443-5460 [PMID: 28814862]
  22. Acta Pharmacol Sin. 2016 Sep;37(9):1229-36 [PMID: 27546005]
  23. Avicenna J Med Biotechnol. 2018 Oct-Dec;10(4):208-213 [PMID: 30555652]
  24. Vaccine. 1992;10(4):238-42 [PMID: 1561830]
  25. Immunity. 2022 May 10;55(5):749-780 [PMID: 35545027]
  26. Immunol Lett. 2020 Jan;217:116-125 [PMID: 31669546]
  27. Vaccine. 2016 Dec 12;34(51):6464-6471 [PMID: 27866773]
  28. J Virol. 2010 Sep;84(17):8369-88 [PMID: 20534862]
  29. Viruses. 2012 Dec 10;4(12):3606-24 [PMID: 23223215]
  30. Int J Nanomedicine. 2011;6:765-74 [PMID: 21589644]
  31. Mol Ther. 2011 Mar;19(3):602-11 [PMID: 20959813]
  32. Biomark Res. 2020 Sep 29;8:49 [PMID: 33005420]
  33. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7297-301 [PMID: 7638184]
  34. Dis Mon. 2017 Sep;63(9):251-256 [PMID: 29737282]
  35. J Control Release. 2023 Oct;362:667-691 [PMID: 37666302]
  36. Int J Biol Macromol. 2024 Jul;273(Pt 1):132916 [PMID: 38844287]
  37. Blood. 2003 Jun 15;101(12):4923-9 [PMID: 12609829]
  38. Vaccine X. 2021 Apr 20;8:100097 [PMID: 34041476]
  39. Bioconjug Chem. 2006 Jan-Feb;17(1):152-8 [PMID: 16417264]
  40. J Allergy Clin Immunol. 2024 Feb;153(2):487-502.e9 [PMID: 37956733]
  41. Acta Pharmacol Sin. 2013 Mar;34(3):432-40 [PMID: 23334235]
  42. Curr Opin Mol Ther. 2000 Apr;2(2):188-98 [PMID: 11249641]
  43. Dev Comp Immunol. 2020 Feb;103:103492 [PMID: 31494219]
  44. Immunity. 2005 Apr;22(4):493-505 [PMID: 15845453]
  45. Cancer Gene Ther. 2012 Dec;19(12):880-7 [PMID: 23099886]

Grants

  1. China and "Fengcheng Talents Plan" 113 biomedical Special grant of Taizhou, China./Taizhou, China.
  2. Special funding for basic research/Ab & B Bio-Tech CO., LTD. JS, Taizhou, Jiangsu, China

Word Cloud

Created with Highcharts 10.0.0DNAinfluenzamucosalvirusCCL19vaccineimmunityH7N9vaccinesdeliveryPEICSAIVholdssubstantialimmunogenicityimmunizationstudyeffectmolecularadjuvantchitosannasalresultscellularhumoralHABACKGROUND/OBJECTIVES:avianconstitutesnovelsubtypeemergedwithinpastdecadeEmpiricalstudiesdemonstratedpotentialtriggerhumanpandemicVaccinesconstitutesolearmamentavailablehumanitycombatingepidemicspresentnumerousmeritshoweverconundrumspersistregardingaugmentimplementMETHODS:BALB/cmiceutilizedmodelinvestigatedetermineimmuneresponseelicitedpolyethyleneimineadjuvantsrouteRESULTS:revealedexertsimmunomodulatoryenhancementH7N9-HAinducingpronouncedAdditionallyindicatedcompositeformedHA-CCL19combinationeffectivelyactivateslocalwellsystemicoffering100%protectionlethaldoseshomologouschallengesCONCLUSIONS:conspicuouslyaugmentsconservesintegrityantigenSimultaneouslyproficientlyfacilitatetherebyelicitingrelatedinvestigatedfeasibilityutilizingmucosasignificantimplicationsadvancementapplicationpublichealthIntranasalImmunizationVaccineHA-CCL19/Polyethylenimine/ChitosanCompositeProvidesImmuneProtectionInfectionHA-CCL19/poly-ethylenimine/chitosanpolyethyleneimine

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