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Enhancement of intranasal mucosal immunization of mucosal vaccines by ultrasonic treatment

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Abstract

The pathogens of most infectious diseases invade the host through mucosal sites, and immunization with mucosal vaccines is the best means of combating these infectious diseases. Oral delivery and nasal delivery are the most common methods of mucosal vaccination. However, the delivery process is inefficient, and mucosal vaccination is ineffective because the vaccine formulation is easily and rapidly removed and has difficulty in crossing the mucosal surface. In this paper, we investigated whether the mucosal immune response could be enhanced by ultrasound facilitation of nasal mucosal delivery of vaccine preparations. For this purpose, we used manganese dioxide (MnO2) as the vaccine carrier/adjuvant, coated with chitosan oligosaccharide (COS) to enhance mucosal adsorption, and further physically adsorbed model antigen ovalbumin (OVA) to construct a nanoparticulate vaccine formulation MnO2@COS@OVA. Ultrasound treatment was found to promote antigen delivery and recruitment of dendritic cells (DCs) and macrophages as well as T-cell infiltration in nasal mucosal tissues through nasal mucosal immunization studies. With ultrasound assistance, MnO2@COS@OVA particles promoted the maturation of DCs in vitro and in vivo and promoted the production of effector memory T cells in vivo and cytokine secretion by splenocytes in vitro. In particular, ultrasound treatment significantly increased the levels of secretory IgA antibodies in the nasal mucosa and genital tract mucosa of experimental mice. In addition, the experimental data showed that the MnO2@COS@OVA particles had good biocompatibility and caused no significant damage to the nasal mucosal and vital organ tissue. These data suggest that ultrasound treatment can promote the induction of efficient immune responses to mucosal vaccines and provide new ideas for the opening and clinical translation of mucosal vaccines.

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Acknowledgements

This work was supported by the National Key R&D Program of China (No. 2018YFC0311103).

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Author notes

  1. Haowei Xu and Yang Liao have contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China

    Haowei Xu & Zonghua Liu

  2. Department of Laboratory Medicine, General Hospital of Southern Theatre Command of PLA, Guangzhou, 510010, China

    Yang Liao

  3. Institute of Physiology of NAS of Belarus, Minsk, Belarus

    Mankovskaya Svetlana

  4. Department of Cardiology, Heyuan Shenhe People’s Hospital, The Fifth Affiliated Hospital, Jinan University, Heyuan, 517475, China

    Deguang Yang & Huaibin Wan

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Contributions

HWX: conceptualization, investigation, writing—original draft. YL: methodology, formal analysis, data curation. MS: validation. DGY: resources. HBW: supervision, funding acquisition, validation. ZHL: project administration, funding acquisition, writing—review & editing.

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Correspondence to Huaibin Wan or Zonghua Liu.

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Ethical approval

All animal experiments in this study followed animal ethics and Jinan University guidelines (Ethics Approval Number: 20211116-04).

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Xu, H., Liao, Y., Svetlana, M. et al. Enhancement of intranasal mucosal immunization of mucosal vaccines by ultrasonic treatment. Bio-des. Manuf. 6, 405–422 (2023). https://doi.org/10.1007/s42242-023-00231-9

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