# Comparative Evaluation of Carbohydrate, Amino Acid, and Ionic Liquid Excipients for Flavivirus Vaccine Stabilization

## TL;DR

This study compares different additives to stabilize flavivirus vaccines, finding that combinations of trehalose and histidine work best.

## Contribution

The novel finding is that trehalose-histidine combinations significantly outperform other excipients in stabilizing flavivirus vaccines.

## Key findings

- Trehalose and sucrose provided the greatest stabilization among carbohydrates.
- Histidine was the most effective amino acid for stabilization.
- Trehalose-histidine combinations preserved viral infectivity up to 19.4-fold better than buffer controls.

## Abstract

Live-attenuated flavivirus
vaccines (yellow fever, dengue,
and
Japanese encephalitis) exhibit poor thermal stability in liquid formulations,
requiring lyophilization and storage between 2 and 8 °C to maintain
potency. We evaluated carbohydrates, amino acids, and choline-based
ionic liquids as preservatives for vaccine-like flavivirus. Among
the carbohydrates tested, trehalose and sucrose provided greatest
stabilization, while histidine demonstrated the strongest stabilizing
effect among amino acids. Trehalose-histidine and sucrose-histidine
combinations produced synergistic effects, preserving viral infectivity
more effectively than individual components. Choline chloride and
choline acetate formulations, despite their established efficacy
in protein stabilization, demonstrated limited enhancement of flavivirus
thermal stability compared to carbohydrate-amino acid formulations.
Trehalose-histidine combinations provided up to 19.4-fold improved
titer retention compared to buffer controls, with consistent superiority
across all three flavivirus species tested, while choline-based ionic
liquid formulations showed moderate stabilizing effects but were consistently
outperformed by carbohydrate-amino acid approaches.