Intranasal Vaccine Delivery Technology for Respiratory Tract Disease Application with a Special Emphasis on Pneumococcal Disease

Walkowski, William; Bassett, Justin; Bhalla, Manmeet; Pfeifer, Blaine A.; Ghanem, Elsa N. Bou

doi:10.3390/vaccines9060589

Cited by 6 publications

(4 citation statements)

References 145 publications

(172 reference statements)

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“…To evaluate the effect of A. fumigatus EVs in vivo , mice were initially intranasally immunized with EV preparations; considered the main route of infection by the fungus ( Dagenais and Keller, 2009 ). The intranasal route of administration offers the advantage of being less invasive and stimulating mucosal and systemic responses ( Walkowski et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Pre-Exposure With Extracellular Vesicles From Aspergillus fumigatus Attenuates Inflammatory Response and Enhances Fungal Clearance in a Murine Model Pulmonary Aspergillosis

Souza

Gurgel

Malacco

et al. 2022

Front. Cell. Infect. Microbiol.

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Aspergillus fumigatus is a ubiquitous and saprophytic filamentous fungus and the main etiologic agent of aspergillosis. Infections caused by A. fumigatus culminate in a strong inflammatory response that can evolve into respiratory failure and may be lethal in immunocompromised individuals. In the last decades, it has been demonstrated that extracellular vesicles (EVs) elicit a notable biological response in immune cells. EVs carry a variety of biomolecules, therefore are considered potential antigen delivery vehicles. The role of EVs as a strategy for modulating an effective response against infections caused by A. fumigatus remains unexplored. Here we investigate the use of EVs derived from A. fumigatus as an immunization tool to induce a more robust immune response to A. fumigatus pulmonary infection. In order to investigate that, male C57BL/6 mice were immunized with two doses of EVs and infected with A. fumigatus. Pre-exposure of mice to EVs was able to induce the production of specific IgG serum for fungal antigens. Besides that, the immunization with EVs reduced the neutrophilic infiltrate into the alveoli, as well as the extravasation of total proteins and the production of proinflammatory mediators IL-1β, IL-6, and CXCL-1. In addition, immunization prevented extensive lung tissue damage and also improved phagocytosis and fungus clearance. Noteworthy, immunization with EVs, associated with subclinical doses of Amphotericin B (AmB) treatment, rescued 50% of mice infected with A. fumigatus from lethal fungal pneumonia. Therefore, the present study shows a new role for A. fumigatus EVs as host inflammatory response modulators, suggesting their use as immunizing agents.

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Section: Discussionmentioning

confidence: 99%

Pre-Exposure With Extracellular Vesicles From Aspergillus fumigatus Attenuates Inflammatory Response and Enhances Fungal Clearance in a Murine Model Pulmonary Aspergillosis

Souza

Gurgel

Malacco

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Intranasal inoculation has been increasingly developed to combat respiratory pathogens since it can induce a strong antigen-specific immune response in the nasal cavity/lung and then confer superior protection against respiratory infections [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. For example, the intranasal administration of a live attenuated influenza vaccine (LAIV) has been clinically used in the USA since 2003.…”

Section: Challenges and Solutions For The Development Of Mucosa-targe...mentioning

confidence: 99%

Strategies to Develop a Mucosa-Targeting Vaccine against Emerging Infectious Diseases

Feng

Wen

Chen

et al. 2022

Viruses

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Numerous pathogenic microbes, including viruses, bacteria, and fungi, usually infect the host through the mucosal surfaces of the respiratory tract, gastrointestinal tract, and reproductive tract. The mucosa is well known to provide the first line of host defense against pathogen entry by physical, chemical, biological, and immunological barriers, and therefore, mucosa-targeting vaccination is emerging as a promising strategy for conferring superior protection. However, there are still many challenges to be solved to develop an effective mucosal vaccine, such as poor adhesion to the mucosal surface, insufficient uptake to break through the mucus, and the difficulty in avoiding strong degradation through the gastrointestinal tract. Recently, increasing efforts to overcome these issues have been made, and we herein summarize the latest findings on these strategies to develop mucosa-targeting vaccines, including a novel needle-free mucosa-targeting route, the development of mucosa-targeting vectors, the administration of mucosal adjuvants, encapsulating vaccines into nanoparticle formulations, and antigen design to conjugate with mucosa-targeting ligands. Our work will highlight the importance of further developing mucosal vaccine technology to combat the frequent outbreaks of infectious diseases.

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“…基于鼻腔独特的生理结构，鼻腔药物递送系统还被开发用于免疫治疗，如流感疫苗、2019冠状病毒病疫苗等［ 14 - 15 ］。鼻腔免疫途径是黏膜系统免疫途径的重要组成部分，鼻腔生理环境温和，抗原诱导免疫反应的阈值较低，且鼻腔血管化程度高，使得疫苗和佐剂的起效剂量更低［ 16 ］。同时，鼻腔黏膜系统是呼吸道的对外开放窗口，疫苗经鼻腔接种可模拟呼吸道病毒的天然感染途径，在上呼吸道形成第一线保护性免疫应答，具有快速起效、持久保护、应急保护等独特优势，是全身疫苗接种的良好替代途径，亦是呼吸道疫苗接种的重要途径［ 17 - 18 ］。…”

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Factors affecting nasal drug delivery and design strategies for intranasal drug delivery

HU,

YUE,

et al. 2023

J Zhejiang Univ (Med Sci)

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鼻腔药物递送系统是一种非侵入式给药途径，具有无首过效应、快速起效、脑靶向等优势，是注射给药的一种可行替代途径，亦是中枢神经系统潜在的给药途径。但鼻腔生理环境复杂，且鼻腔药物递送系统为“药械合一”类制剂，药物经鼻递送效率受药物、制剂、装置及鼻腔生理等多因素影响。通过改变药物理化性质、制剂中添加酶抑制剂或吸收促进剂、设计新型药物载体等策略，改善药物的溶解性、稳定性、膜渗透性和鼻腔滞留时间，可以提高鼻腔药物递送效率。本文对鼻腔药物递送系统的影响因素和设计策略进行了综述，旨在为鼻腔药物递送系统的设计提供依据和思路。

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Intranasal Vaccine Delivery Technology for Respiratory Tract Disease Application with a Special Emphasis on Pneumococcal Disease

Cited by 6 publications

References 145 publications

Pre-Exposure With Extracellular Vesicles From Aspergillus fumigatus Attenuates Inflammatory Response and Enhances Fungal Clearance in a Murine Model Pulmonary Aspergillosis

Pre-Exposure With Extracellular Vesicles From Aspergillus fumigatus Attenuates Inflammatory Response and Enhances Fungal Clearance in a Murine Model Pulmonary Aspergillosis

Strategies to Develop a Mucosa-Targeting Vaccine against Emerging Infectious Diseases

Factors affecting nasal drug delivery and design strategies for intranasal drug delivery

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