What Is the MPL Adjuvant and How Does It Work?
Explore the MPL adjuvant, a key vaccine component engineered from a bacterial molecule to safely guide the immune system toward a precise and effective response.
An adjuvant is a substance included in some vaccines to generate a stronger immune response. Many modern vaccines are constructed from small, specific components of a pathogen, like a single protein, rather than the entire germ. These components alone may not be enough to provoke a sufficiently protective immune reaction. An adjuvant like Monophosphoryl lipid A (MPL) serves as a supplement to enhance the body’s response to the vaccine’s antigen.
The Origin of MPL
Monophosphoryl lipid A originates from lipopolysaccharide (LPS), a structural component of the outer membrane of gram-negative bacteria, such as Salmonella minnesota. LPS is a strong stimulator of the immune system because the body recognizes it as a sign of bacterial invasion. However, this activity makes the unaltered LPS molecule too toxic for direct use in human vaccines, as it can cause an overstimulation of the immune system.
To harness the properties of LPS without the toxicity, the molecule undergoes a detoxification process. This involves chemical steps that selectively remove parts of the LPS molecule responsible for its harmful effects, specifically a phosphate group and a fatty acid chain. The result is Monophosphoryl lipid A, a derivative that retains immune-stimulating capabilities but is at least 100 times less toxic than its precursor. This modification allows MPL to be a safe component in vaccine formulations.
How MPL Stimulates the Immune System
MPL interacts with a specific part of the innate immune system. It acts as an agonist for Toll-like receptor 4 (TLR4), a protein on the surface of immune cells like dendritic cells and macrophages. These cells are part of the body’s first line of defense. TLR4 is a pattern recognition receptor, evolved to recognize molecular patterns associated with microbes, like the structure of MPL.
When MPL binds to TLR4, it initiates a signaling cascade within the cell. This activation triggers the production and release of various cytokines, which are proteins that signal to other immune cells. The specific cytokines produced guide the adaptive immune response toward a T-helper 1 (Th1) profile. A Th1-biased response is effective at activating cellular immunity, which is necessary for clearing cells infected with viruses.
By activating this pathway, MPL helps shape the quality and intensity of the immune response to the vaccine antigen. It directs the immune system to build a defense tailored to the threat the vaccine is designed to protect against. This allows for a stronger and more long-lasting immunity.
MPL in Modern Vaccines
MPL is a component of several modern vaccines, particularly those requiring a strong cell-mediated immune response. It is a feature of Adjuvant System 04 (AS04), where MPL is combined with aluminum salts. This combination is used in Cervarix, a vaccine for the human papillomavirus (HPV), enhancing the immune response.
MPL is also a component of Adjuvant System 01 (AS01), used in the shingles vaccine, Shingrix. In AS01, MPL is combined with another immune-stimulator, QS-21, and delivered within a liposomal formulation. This formulation is designed to elicit a strong T-cell response, which is important for controlling the varicella-zoster virus that causes shingles.
By combining MPL with other components like alum or QS-21, formulators can create a tailored immune response for a specific pathogen or patient population. This strategy allows for effective vaccines where a simple antigen-plus-alum formulation would be insufficient.
The Safety Profile of MPL Adjuvants
The safety of MPL is linked to its origin as a detoxified derivative of bacterial LPS. The chemical modifications that remove the toxic parts of the LPS molecule are the reason for its good safety profile, making it well-tolerated in humans.
Vaccines containing MPL can cause more local and systemic reactions than non-adjuvanted vaccines. Common side effects include temporary pain, redness, or swelling at the injection site, as well as transient flu-like symptoms. These reactions are mild and indicate the adjuvant is activating the immune system.
Extensive clinical trials and post-market use have confirmed the safety of MPL-containing adjuvants. Formulations like AS01 and AS04 have been administered to millions of individuals since their approval.