What is trehalose?
Trehalose, chemically known as α-D-glucopyranosyl-(1,1)-α-D-glucopyranoside, consists of two glucose molecules joined by an α,α-1,1-glucosidic linkage. This unique structure grants trehalose exceptional stability and versatility, making it highly desirable for numerous applications.
Common applications of trehalose
- In healthcare, trehalose may have antioxidant, anti-inflammatory, and immunomodulatory properties and is therefore being explored for use in neurodegenerative diseases.
- In the food industry, trehalose is used as a food additive due to its ability to improve the stability and shelf life of various products.
- In addition, trehalose is also popular in the cosmetic industry for its moisturizing and hydrating properties.
- What's more worth mentioning is that in the field of biotechnology, trehalose can protect cells from stress and preserve them better, so it can be used in various medical and pharmaceutical products, such as vaccines, proteins and transplanted cells.
Stabilizing mechanism of trehalose on biomolecules
Trehalose, a highly adaptable stabilizer, has been successfully utilized in various biomedical formulations. Although its extensive usage, the exact mechanism of stabilization is still a matter of debate, likely influenced by environmental factors and the specific molecule being stabilized. The various theories proposed for trehalose stabilization comprise :
- Water entrapment or preferential exclusion
- Water replacement
For example, Christoffer Olsson, et al. studied the mechanism of action of trehalose in stabilizing proteins. The results show that the preferential hydration model is suitable for this myoglobin-trehalose system.
Schematic of the protein-trehalose-water system. 
What role does trehalose play in vaccines?
Trehalose helps protect the vaccine components (antigens, adjuvants, etc.) from degradation during storage and transportation. It forms a glassy state when the vaccine is dried, preserving the structure and function of the biological molecules.
Trehalose enables vaccines to undergo freeze-drying (lyophilization), a process used to remove water from the formulation, thereby improving long-term stability. It prevents the formation of ice crystals that could damage the vaccine's structure.
- Preservation of antigenicity
Trehalose helps maintain the immunogenicity of vaccines by preserving the conformational structure of antigens and preventing their denaturation during storage.
In some cases, vaccines are provided as a dry powder that requires reconstitution with a liquid before administration. Trehalose acts as a cryoprotectant, preventing damage to the vaccine components during the reconstitution process.
Research progress of trehalose in vaccine development
Over the years, research has been conducted to examine the potential of trehalose in vaccine development. Below we briefly outline several research progresses of trehalose in vaccine development:
- Specialized vaccine diluents based on trehalose can be used to improve the stability of the Peste des Petits Ruminants (PPR) vaccine under dilution conditions. 
- Spray-drying influenza antigens containing trehalose and leucine produces aerosolizable powder vaccine formulations.
The spray-dried trehalose/leucine formulations containing HA antigen. 
- The trehalose-glycerol natural deep eutectic solvent system can be used to store influenza hemagglutinin (HA) display virus-like particles (VLP). 
- Daniele Vinciguerra, et al. JACS Au, 2022, 2(7), 1561-1587.
- Christoffer Olsson, et al. J. Phys. Chem. B, 2016, 120(20), 4723-4731.
- Mohanto, N., et al. Bangladesh Journal of Veterinary Medicine (BJVM), 2019, 17(2), 117-123.
- Sou, Tomás, et al. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2015, 28(5), 361-371.
- Ricardo Correia, et al. Vaccine, 2021, 39(24), 3279-3286.
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