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✍️ Rachel Legg | MBiochem Biochemistry student at the Uni of Bath
What are inverse vaccines? 💉
Inverse vaccines are a new type of vaccine that have the potential to revolutionise the treatment of autoimmune conditions, such as multiple sclerosis, type 1 diabetes and coeliac disease.
A typical vaccine aims to activate the body's immune response to a specific virus or bacteria that poses a threat. In contrast, an inverse vaccine, also called a tolerogenic vaccine, deactivates an immune response by introducing the body's own antigens (autoantigens) in a specific manner to induce tolerance.
This has the potential to be used as a new therapy to treat autoimmune diseases, allergies, and to combat organ transplant rejection.
Researchers at the University of Chicago Pritzker School of Molecular Engineering are working to improve our understanding of inverse vaccines.
How do inverse vaccines work? 🔬
Inverse vaccines introduce autoantigens to the immune system in a way that induces tolerance to them.
Research into inverse vaccines as a therapeutic treatment for autoimmune diseases dates back to the immunologist Lawrence Steinmen in the 1990s. But, in 2023, a recent breakthrough was reported by a team of researchers at the University of Chicago, led by immunoengineer Jeffrey Hubbell. Their research finds a way to introduce autoantigens in a way that mimics peripheral immune tolerance.
Peripheral tolerance occurs in the liver, ensuring that self-reactive T cells that have the potential to cause autoimmune diseases by attacking damaged body cells, are either deleted via apoptosis or become unresponsive to the relevant antigen (anergic). Researchers at the University of Chicago found that tagging a molecule with N-acetylgalactosamine can mimic this tolerance process by sending the molecule to the liver where the immune system then learns not to attack this specific molecule. Injecting a patient with a tagged autoantigen could therefore teach the immune system not to attack this molecule, combatting autoimmune conditions like multiple sclerosis and type 1 diabetes where the body attacks its own cells.
Potential drug delivery systems for an inverse vaccine include:
PLGA microparticles
Polymer-based nanoparticles
Virus-like particles
Liposomes
How do inverse vaccines compare to current treatment for autoimmune conditions? 💊
Inverse vaccines are more specific than current therapies and could lead to reduced side effects.
Current treatments for autoimmune diseases, such as disease-modifying therapies like alemtizimab (under the brand name Lemtrada) and teriflunomide (under the brand name Aubagio) for multiple sclerosis, generally tend to reduce inflammation and slow the progression of the disease. However, these kinds of treatments are often immunosuppressive, resulting in increased risk of infections and cancer due to a compromised immune system. In contrast, inverse vaccines involve reducing an immune response to a specific autoantigen, meaning that the side effects of broader immune suppression would not occur- ultimately reducing the potential treatment burden.
In addition, inverse vaccines could treat diseases after inflammation has already begun, which, as Hubbell commented, "is more useful in a real-world context.” Inverse vaccines, unlike many current therapies, could have the potential to treat the underlying immune dysfunction causing an autoimmune disease.
What is the current stage of inverse vaccine research? 💡
There are currently no clinically approved inverse vaccines, but research into this new therapeutic treatment is advancing quickly.
In mouse models with a multiple sclerosis-like disease, inverse vaccine treatment was found to significantly lower disease severity and restore nerve function. Similar results were seen in mouse models of coeliac disease.
Trials into inverse vaccines for humans are still in the early stages - the biotech company Anokion is carrying out phase I safety trials for the vaccine ANK-700 to treat multiple sclerosis. Preliminary biomarker data from this trial has suggested that ANK-700 is safe and can induce immune tolerance.
What are the challenges of inverse vaccine development? 💪
As inverse vaccines are still in the early stages of research, there are multiple challenges to be overcome before they can be made publicly available.
Identifying the specific autoantigen responsible for causing an autoimmune disease (of which there can be multiple).
Completing inverse vaccine clinical trials that determine the safety and efficacy in humans, ensuring that the vaccine does not provoke an increased immune response.
Gaining high specificity of the vaccine, as even slight changes in the autoantigen's structure could result in an unpredictable immune response.
Inverse vaccines, if they continue to show promise in early trials, are likely years away from reality. However, they have the potential to improve the treatment of a group of diseases that affect 10% of the global population.
Edited by: Olivia Laughton | Lead Content Editor | BSc Microbiology, University of Leeds
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