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– A Research Article –

Lipid-based adjuvants in vaccines

Adjuvants are added to vaccines to boost their efficiency, but the
underlying molecular mechanisms used to be poorly understood.

About the author


A photo of Henri Deda.
Henri Deda
Communications Officer at Lipotype

Henri Deda studied molecular Biotechnology at TU Dresden. At Lipotype, he developed a communication approach driven by providing access to expert knowledge to everyone.

Resources


Activation of the endoplasmic reticulum…

Givord et al. | npj Vaccines (2018)


An automated shotgun lipidomics platform…

Surma et al. | EJLT (2015)


Systematic screening for novel lipids by…

Papan et al. | Anal. Chem. (2014)


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Summary

• Lipidomics revealed mode of action of vaccine components
• Oil-in-water adjuvants are potent immunostimulatory agents
• Lipid metabolism results pave the way to novel adjuvants

A photo of Henri Deda.
Henri Deda
Communications Officer at Lipotype

THE measles, the flu, or the world-gripping COVID-19 – ever changing pathogens are constantly threatening mankind. Pharma research is permanently challenged to find a cure or even a protection in order to make the world a safer place. They look back on a tremendous track record, having developed vaccines against polio or smallpox for example. But they are also under constant attack by critics that fear possible side-effects of the injections.

A graphic representation of how vaccines work from introducing safe amounts of antigens to the body to developing antibodies for future infections.

Vaccines train the immune system to recognize pathogens. To achieve that, they introduce antigens to the body to trigger an immune response. Vaccine development can count on agents that enhance the impact of the antigens in the human body by triggering a stronger immune reaction with fewer antigen.

These vaccine components are called adjuvants, they are the magic sauce of modern vaccines. Some of them boost antibody production or activate T-cells, thus minimizing the needed amount of injected material – all while having little to very limited pharmaceutical effect themselves. Adjuvants are the key component to ensure even the smallest doses and the fewest pathogen particles trigger a long-term immune response in the body.

QUOTE

Science looks back on a history of a hundred years of adjuvant research and might now witness a breakthrough in the development of novel adjuvants from the lipid spectrum.

Prof. Dr. Kai Simons
Prof. Dr. Kai Simons
Emeritus Director of the MPI-CBG and founder of Lipotype

One of the few approved adjuvants is the lipid-based Adjuvant System 03 (AS03). It is an oil-in water emulsion believed to induce a local inflammatory response that triggers the desired stronger reaction in the innate immune system.

Lipid-based adjuvants are believed to play an important role in the efficiency of vaccines, yet the molecular mechanisms behind their triggering effect had not been illuminated yet. By applying lipidomics, researchers have been able to shine a light on AS03’s effect on lipid metabolism and changes in lipid composition triggered by the adjuvant.

Scientific images showing AS03 inducing the rapid formation of lipid droplets in macrophages and thereby activating the endoplasmic reticulum stress sensor IRE1α contributing to immunostimulatory properties.

AS03 induces the rapid formation of lipid droplets in macrophages: Activation of the endoplasmic reticulum stress sensor IRE1α by the vaccine adjuvant AS03 contributes to its immunostimulatory properties
Charlotte Givord et al., npj Vaccines (2018), doi: 10.1038/s41541-018-0058-4

After injection, AS03 is transported to nearby lymph nodes where it rapidly alters gene expression. Pathway analysis of the altered expression profile highlighted a cluster of down-regulated genes related to lipid metabolism enzymes in lymph nodes. To research the consequences of AS03 injection on molecular level, a global lipidomics analysis of macrophages, a type of white blood cells of the immune system that digest pathogens and defective cells, was applied.

The lipidomics analysis demonstrated that AS03 affects cholesterol and fatty acid metabolism of macrophage cells in lymph nodes, showing a decrease of cholesterol but an increase of phosphatidylcholine lipids, a class of phospholipids. The alteration of the cellular phospholipid composition leads to disorder of one particular compartment of the cell: the endoplasmic reticulum (ER). This is known as ER stress.

Eventually, the ER stress results in an upregulation of immunity pathways and increase of cytokine production to induce a protective immune response. Taken together, lipid metabolism changes induced by AS03 proved to be the reason for the immunostimulatory properties of the adjuvant. Ultimately, these findings pave the way for the development of new vaccine adjuvants.

Lipids might be the key to modern immunology and drug design. A better understanding of the little-known mode of action of adjuvants and other lipids in the human body will help design better drugs and vaccines. Researching the paths and secrets of the lipid metabolism with Lipotype Shotgun Lipidomics analysis provides access to new dimensions for vaccine researchers and pharma.



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