Dry influenza vaccines: towards a stable, effective and convenient alternative to conventional parenteral influenza vaccination

Abstract

Cold-chain requirements, limited stockpiling potential and the lack of potent immune responses are major challenges of parenterally formulated influenza vaccines. Decreased cold chain dependence and stockpiling can be achieved if vaccines are formulated in a dry state using suitable excipients and drying technologies. Furthermore, having the vaccine in a dry state enables the development of non-parenteral patient friendly dosage forms: microneedles for transdermal administration, tablets for oral administration, and powders for epidermal, nasal or pulmonary administration. Moreover, these administration routes have the potential to elicit an improved immune response. This review highlights the rationale for the development of dried influenza vaccines, as well as processes used for the drying and stabilization of influenza vaccines; it also compares the immunogenicity of dried influenza vaccines administered via non-invasive routes with that of parenterally administered influenza vaccines. Finally, it discusses unmet needs, challenges and future developments in the field of dried influenza vaccines.

Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

“…To our knowledge, this is the first study to show that an effective Advax-adjuvanted dry powder influenza vaccine formulation with full retention of biological activity of the WIV antigen and the Advax adjuvant can be prepared by SFD. Though both liquid and dry powder influenza vaccine formulations can be used for pulmonary administration, a dry powder formulation is preferable due to its long-term stability at ambient temperatures, which facilitates stockpiling [10,57,58]. In cases of an influenza pandemic, a stockpiled dry powder formulation would be readily available and easy to administer in mass vaccination campaigns.…”

“…administration for preventing influenza associated illness [8]. Pulmonary vaccines can be delivered as liquids or as dry powders [6,9,10]. In pre-clinical studies, pulmonary delivery of both liquid and dry powder influenza vaccine formulations has shown to induce mucosal as well as systemic immune responses [6,7,11,12].…”

Development of SARS-CoV-2 vaccines: should we focus on mucosal immunity?

“…For instance, decorating VLPs with variant specific surface proteins from Giardia lamblia has allowed to effectively induce, upon oral administration, immunoprotection against influenza and cancer in murine models [34]. The cases of the nasal influenza vaccine licensed for human use and the development of dried formulations to be administered by noninvasive routes illustrate the potential of mucosal vaccines to surpass the difficulties during their developmental path [35]. Moreover, other mucosal routes are acquiring special interest in vaccinology.…”

Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems

“…However, it should be kept in mind that small antigen dose (typically less than 1 mg) can be administered via coated microneedles, due to the limited dimensions of microneedles shaft and tip -thick coatings are generally accompanied with a very low skin delivery efficacy because of a reduced sharpness of microneedle arrays (82,86). Composition of coating solution depends on the nature and type of antigen investigated and commonly includes viscosity enhancer (e.g., carboxymethylcellulose (CMC), methylcellulose) to achieve sufficient thickness of coating layer, stabilizing saccharide (e.g., trehalose, sucrose) to retain activity of antigen during drying/storage and surfactant (e.g., poloxamers) to decrease the surface tension and thus to assure uniform coating efficiency (95,96). Additionally, Choi and co-workers (97) observed that addition of viscosity enhancers was necessary to reduce the osmotic stress (caused by high concentrations of sugars) and to preserve activity of completely inactivated influenza virus during the microneedle coating.…”