Development of a thermostable nanoemulsion adjuvanted vaccine against tuberculosis using a design-of-experiments approach

Abstract

BackgroundAdjuvants have the potential to increase the efficacy of protein-based vaccines but need to be maintained within specific temperature and storage conditions. Lyophilization can be used to increase the thermostability of protein pharmaceuticals; however, no marketed vaccine that contains an adjuvant is currently lyophilized, and lyophilization of oil-in-water nanoemulsion adjuvants presents a specific challenge. We have previously demonstrated the feasibility of lyophilizing a candidate adjuvanted protein vaccine against Mycobacterium tuberculosis (Mtb), ID93 + GLA-SE, and the subsequent improvement of thermostability; however, further development is required to prevent physicochemical changes and degradation of the TLR4 agonist glucopyranosyl lipid adjuvant formulated in an oil-in-water nanoemulsion (SE).Materials and methodsIn this study, we took a systematic approach to the development of a thermostable product by first identifying compatible solution conditions and stabilizing excipients for both antigen and adjuvant. Next, we applied a design-of-experiments approach to identify stable lyophilized drug product formulations.ResultsWe identified specific formulations that contain disaccharide or a combination of disaccharide and mannitol that can achieve substantially improved thermostability and maintain immunogenicity in a mouse model when tested in accelerated and real-time stability studies.ConclusionThese efforts will aid in the development of a platform formulation for use with other similar vaccines.

Vaccine development and delivery strategies – A glimpse

“…Virosomes have been processed by spray drying [22]. Similarly for tuberculosis lyophilization of oil-in-water nano emulsion adjuvants has been worked upon to yield stable product [23]. Human papillomavirus capsomere has been delivered as heat-stable microparticles.…”

Multifactorial Design of a Supramolecular Peptide Anti-IL-17 Vaccine Toward the Treatment of Psoriasis

“…Multifactorial experimental designs are commonly employed in a broad range of technical fields to efficiently optimize a desired outcome while simultaneously gaining knowledge about how multiple factors may interact. Although traditionally underutilized in biological settings, such designs have been receiving increasing attention recently (43,(52)(53)(54). We chose to employ this methodology to investigate how epitope content influenced overall titer and avidity, using a 2 × 2 full factorial design with a center point (Figures 4A,D).…”

Nanotechnological strategies for systemic microbial infections treatment: A review

“…Endowed with greater security, the purified antigens as well as the epitopes synthesized to measure, have great difficulty in generating efficient immune responses. Adjuvants such as naonemulsions emerge in the vaccination scenario, arousing interest in view of the benefits provided by this system, such as increased thermostability, increased immunogenic response, increased immunity availability of the antigen, among others ( Kramer et al, 2018 ). When the adjuvant is co-administered together with antigens, they interact as immunomodulators and / or immunostimulators, becoming immunologically promising ( Csaba et al, 2009 ).…”