Stability Studies of the Vaccine Adjuvant U-Omp19

Abstract

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.

A novel defined TLR3 agonist as an effective vaccine adjuvant

“…Manufacturing of NVT is highly reproducible without sequence errors in PCR and IVT steps (data not shown), indicating that NVT can be mass-produced as an identical material with batch-to-batch consistency. Considering that the physical instability of the adjuvant to temperature changes can lead to loss of vaccine efficacy even within the cold chains ( 32 ), the long-term stability of NVT as determined by the accelerated stability test condition will be a huge advantage for commercial manufacturing, storage, and shipping of the final vaccine product.…”