Advances in intranasal vaccine delivery: A promising non-invasive route of immunization

Kehagia, Eleni; Papakyriakopoulou, Paraskevi; Valsami, Georgia

doi:10.1016/j.vaccine.2023.05.011

Cited by 20 publications

(19 citation statements)

References 108 publications

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“…The significance of the MOD device also extends to the realm of vaccine administration, particularly for vaccines targeting respiratory viruses like influenza or SARS-CoV-2 [44][45][46]. The potential to deliver vaccines effectively to the posterior two-thirds of the nose and nasopharynx, regions rich in ACE2 receptors, could enhance mucosal immunization and contribute to more effective protection against these pathogens [47,48].…”

Section: Clinical Significance and Implications Of The Modified Nasal...mentioning

confidence: 99%

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

Seifelnasr,

Si,

2024

Pharmaceutics

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The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle’s insertion depth, which further affects the initial nasal spray deposition and subsequent translocation, potentially increasing drug wastes and dosimetry variability. To address this issue, we designed a new spray pump that separated the nozzle from the actuator and connected them with a flexible tube, thereby eliminating nozzle retraction during application. The objective of this study is to test the new device’s performance in comparison to the conventional nasal pump in terms of spray generation, plume development, and dosimetry distribution. For both devices, the spray droplet size distribution was measured using a laser diffraction particle analyzer. Plume development was recorded with a high-definition camera. Nasal dosimetry was characterized in two transparent nasal cavity casts (normal and decongested) under two breathing conditions (breath-holding and constant inhalation). The nasal formulation was a 0.25% w/v methyl cellulose aqueous solution with a fluorescent dye. For each test case, the temporospatial spray translocation in the nasal cavity was recorded, and the final delivered doses were quantified in five nasal regions. The results indicate minor differences in droplet size distribution between the two devices. The nasal plume from the new device presents a narrower plume angle. The head orientation, the depth at which the nozzle is inserted into the nostril, and the administration angle play crucial roles in determining the initial deposition of nasal sprays as well as the subsequent translocation of the liquid film/droplets. Quantitative measurements of deposition distributions in the nasal models were augmented with visualization recordings to evaluate the delivery enhancements introduced by the new device. With an extension tube, the modified device produced a lower spray output and delivered lower doses in the front, middle, and back turbinate than the conventional nasal pump. However, sprays from the new device were observed to penetrate deeper into the nasal passages, predominantly through the middle-upper meatus. This resulted in consistently enhanced dosing in the middle-upper turbinate regions while at the cost of higher drug loss to the pharynx.

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Section: Clinical Significance and Implications Of The Modified Nasal...mentioning

confidence: 99%

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

Seifelnasr,

Si,

2024

Pharmaceutics

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“…Noninvasive vaccine delivery methods, including needle-free and liquid-based approaches, hold significant appeal due to their cost effectiveness and potential to address the multiple dosing issues associated with nasal and oral live-attenuated vaccines. , However, current noninvasive formulations often suffer from limited bioavailability due to biological barriers that hinder systemic absorption . Further research is needed to develop potent adjuvants specifically designed to stimulate both mucosal and systemic immune responses.…”

Section: Future Vision Of the Mucosal Vaccinementioning

confidence: 99%

Understanding Mucosal Physiology and Rationale of Formulation Design for Improved Mucosal Immunity

Biswas,

Nurunnabi,

Khatun

2024

ACS Appl. Bio Mater.

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The oral and nasal cavities serve as critical gateways for infectious pathogens, with microorganisms primarily gaining entry through these routes. Our first line of defense against these invaders is the mucosal membrane, a protective barrier that shields the body's internal systems from infection while also contributing to vital functions like air and nutrient intake. One of the key features of this mucosal barrier is its ability to protect the physiological system from pathogens. Additionally, mucosal tolerance plays a crucial role in maintaining homeostasis by regulating the pH and water balance within the body. Recognizing the importance of the mucosal barrier, researchers have developed various mucosal formulations to enhance the immune response. Mucosal vaccines, for example, deliver antigens directly to mucosal tissues, triggering local immune stimulation and ultimately inducing systemic immunity. Studies have shown that lipid-based formulations such as liposomes and virosomes can effectively elicit both local and systemic immune responses. Furthermore, mucoadhesive polymeric particles, with their prolonged delivery to target sites, have demonstrated an enhanced immune response. This Review delves into the critical role of material selection and delivery approaches in optimizing mucosal immunity.

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“…Most of the approved mucosal vaccines employ attenuated pathogens administered orally ( Table 1 ). There have been approximately 30 clinical trials for nasal vaccines, but FluMist ® (a live, attenuated influenza vaccine) remains the only one approved in the United States [ 54 ]. FluMist ® is composed of influenza strains that are temperature-sensitive and cold-adapted, becoming attenuated at body temperature [ 55 , 56 ].…”

Section: Importance Of Mucosal Vaccines and Their Developmentmentioning

confidence: 99%

Vaccine Strategies to Elicit Mucosal Immunity

Song,

Mehl,

Zeichner

2024

Vaccines

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Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles in host immune defense to provide durable and better recall responses. Substantial attention has been focused on developing effective mucosal vaccines to elicit robust localized and systemic immune responses by administration via mucosal routes. Mucosal vaccines that elicit effective immune responses yield protection superior to parenterally delivered vaccines. Beyond their valuable immunogenicity, mucosal vaccines can be less expensive and easier to administer without a need for injection materials and more highly trained personnel. However, developing effective mucosal vaccines faces many challenges, and much effort has been directed at their development. In this article, we review the history of mucosal vaccine development and present an overview of mucosal compartment biology and the roles that mucosal immunity plays in defending against infection, knowledge that has helped inform mucosal vaccine development. We explore new progress in mucosal vaccine design and optimization and novel approaches created to improve the efficacy and safety of mucosal vaccines.

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Advances in intranasal vaccine delivery: A promising non-invasive route of immunization

Cited by 20 publications

References 108 publications

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

Understanding Mucosal Physiology and Rationale of Formulation Design for Improved Mucosal Immunity

Vaccine Strategies to Elicit Mucosal Immunity

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