Excipients play a crucial role in mRNA vaccines:
Protect the fragile mRNA sequence from degradation.
Facilitate delivery of the mRNA into cells and release it from internal compartments.
Modulate immune response: Different lipids can trigger specific types of immune reactions.
Examples of excipients in COVID-19 mRNA vaccines:
Moderna: messenger ribonucleic acid (mRNA), lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose
Pfizer/BioNTech: messenger ribonucleic acid (mRNA), lipids (((4-hydroxybutyl) azanediyl) bis(hexane-6,1-diyl), bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000] N, N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol), potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose.
Functions of Excipients
(Pfizer/BioNTech)
Lipids: Nanolipids, or tiny fat molecules, protect the mRNA and provide a “greasy” exterior that helps the mRNA slide inside cells.
Nanolipid components in the Pfzer-BioNTech vaccine include: ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol
Salts: Helping to balance the acidity in your body, the following salts are included in the Pfzer-BioNTech vaccine: potassium chloride, monobasic potassium phosphate, sodium chloride, and dibasic sodium phosphate dihydrate
Sugar: Basic table sugar, also known as sucrose, can also be found in the Pfzer-BioNTech vaccine. This ingredient helps the molecules maintain their shape during freezing.
(Moderna)
- Lipids: Nanolipids help deliver the mRNA to the vaccine recipient’s cells. Nanolipid components of the Moderna vaccine include: (SM-102, 1,2-dimyristoyl-rac-glycero3-methoxypolyethylene glycol-2000 [PEG2000-DMG], cholesterol, and 1,2-distearoyl-snglycero-3-phosphocholine [DSPC])
- The remaining excipients, including acids (acetic acid), acid stabilizers (tromethamine and tromethamine hydrochloride), salt (sodium acetate), and sugar (sucrose) all work together to maintain the stability of the vaccine after it’s produced.
In 2023, Lizhou Zhang and colleagues reported that the ionizable lipid, SM-102, in Moderna’s vaccine performed better than
ALC-0315 in Pfizer-BioNTech’s vaccine for intramuscular delivery of mRNA
and antibody production in mice and long-term stability at 4 °C.
Moreover, Pfizer-BioNTech’s 5′ UTR and Moderna’s 3′ UTR outperform their
counterparts in their contribution to transgene expression in mice. They further found that varying N1-methylpseudouridine content at the wobble
position of mRNA has little effect on vaccine efficacy. (1)
Benefits of using excipients in mRNA vaccines:
Faster development and production: Easier to adapt existing platforms for new vaccines.
Reduced risk of pre-existing immunity: Compared to viral vector-based vaccines.
More targeted immune response: Can be tailored to specific needs.
Challenges with excipients:
Long-term safety data is limited.
Finding the right combination for different applications.
Overall, excipients are essential components of mRNA vaccines, offering numerous advantages but also requiring further research.
Reference:
Shireesh P. Apte, Excipients and mRNA Vaccines, J. Excipients and Food Chem. 11 (4) 2020.
What Ingredients are in the Covid-19 Vaccine? Connecticut Department of Public Health
(1) Lizhou Zhang et al, Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability, NPJ Vaccines. 2023; 8: 156.
