Stability Studies of the Vaccine Adjuvant U-Omp19

Unlipidated outer membrane protein 19 (U-Omp19) is a novel mucosal adjuvant in preclinical development to be used in vaccine formulations. U-Omp19 holds two main properties, it is capable of inhibiting gastrointestinal and lysosomal peptidases, increasing the amount of co-administered antigen that r...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2021-02, Vol.110 (2), p.707-718
Main Authors: Darriba, M. Laura, Cerutti, María L., Bruno, Laura, Cassataro, Juliana, Pasquevich, Karina A.
Format: Article
Language:English
Subjects:
Analytical biochemistry
Circular dichroism
Light scattering (dynamic)
Lyophilization
Mucosal immunization
Mucosal vaccination
Oral drug delivery
Physicochemical properties
Preformulation
Protease
Protein aggregation
Protein formulation
Stability
Vaccine adjuvants
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Summary:Unlipidated outer membrane protein 19 (U-Omp19) is a novel mucosal adjuvant in preclinical development to be used in vaccine formulations. U-Omp19 holds two main properties, it is capable of inhibiting gastrointestinal and lysosomal peptidases, increasing the amount of co-administered antigen that reaches the immune inductive sites and its half-life inside cells, and it is able to stimulate antigen presenting cells in vivo. These activities enable U-Omp19 to enhance the adaptive immune response to co-administrated antigens. To characterize the stability of U-Omp19 we have performed an extensive analysis of its physicochemical and biological properties in a 3-year long-term stability study, and under potentially damaging freeze-thawing and lyophilization stress processes. Results revealed that U-Omp19 retains its full protease inhibitor activity, its monomeric state and its secondary structure even when stored in solution for 36 months or after multiple freeze-thawing cycles. Non-enzymatic hydrolysis resulted the major degradation pathway for storage in solution at 4 °C or room temperature which can be abrogated by lyophilization yet increasing protein tendency to form aggregates. This information will play a key role in the development of a stable formulation of U-Omp19, allowing an extended shelf-life during manufacturing, storage, and shipping of a future vaccine containing this pioneering adjuvant.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2020.10.011