Shingles (Herpes zoster) is a painful disease caused by the reactivation of the varicella-zoster virus (VZV), the same virus that causes chickenpox. VZV remains dormant in the nervous system after chickenpox and can reawaken decades later, often due to age-related immune decline. Vaccination provides a highly effective defense against this reactivation and its common complication, post-herpetic neuralgia, which can cause long-lasting nerve pain. The current standard vaccine recommended for adults in the United States, Shingrix, is not an mRNA vaccine, but rather a different type of technology known as a recombinant subunit vaccine.
The Technology Behind the Shingles Vaccine
The preferred shingles vaccine, Shingrix, is a recombinant subunit vaccine. This means it uses only a purified component of the virus to stimulate immunity, focusing the immune response on a single, specific viral protein. This approach provides robust protection while eliminating the risk of the vaccine causing the disease itself.
The vaccine has two main components: the antigen and the adjuvant system. The antigen is glycoprotein E (gE), a protein found on the surface of VZV. This gE protein is manufactured using recombinant DNA technology in Chinese Hamster Ovarian (CHO) cells. The second component is the proprietary AS01B adjuvant system, which significantly boosts the immune response to the gE protein.
How Recombinant Subunit Vaccines Work
The mechanism of protection centers on the combination of the gE antigen and the AS01B adjuvant. Glycoprotein E is the specific target the immune system is trained to recognize, as it is abundant on the surface of VZV and necessary for viral replication. Presenting only this single protein directs the immune system to build a highly focused defense that can recognize and neutralize the virus if it attempts to reactivate.
The AS01B adjuvant is instrumental in creating a strong, durable immune response, particularly in older adults whose immune systems are less responsive. This sophisticated formulation contains two immunostimulants: Monophosphoryl lipid A (MPL) and QS-21, packaged within a liposome delivery system. MPL, a detoxified bacterial derivative, activates the innate immune system by signaling through Toll-like Receptor 4 (TLR4), creating a localized inflammatory response.
Activation of the innate immune system recruits antigen-presenting cells (APCs) to the site. These APCs capture the gE protein and travel to the lymph nodes, where they present the antigen to T-cells, initiating a profound adaptive immune response. QS-21, derived from the Quillaja saponaria tree, further enhances this process, promoting the generation of gE-specific CD4+ T-cells and high levels of antibodies. The synergistic action of MPL and QS-21 ensures the resulting immunity is long-lasting, providing protection exceeding 90% in adults over 50.
Comparing Recombinant and mRNA Vaccine Approaches
The fundamental difference between recombinant subunit vaccines and mRNA vaccines lies in the delivery mechanism. A recombinant vaccine, like Shingrix, delivers a manufactured protein directly into the body. The gE protein is produced in a lab, purified, and then formulated into the final dose.
In contrast, an mRNA vaccine delivers genetic instructions (messenger RNA) that teach the body’s own cells how to temporarily produce the viral protein. After injection, the mRNA enters the cell’s machinery, which reads the instructions and builds the target protein. This protein is then displayed on the cell surface, prompting the immune system to recognize it and mount a protective response.
The approaches also differ in manufacturing and storage requirements. Recombinant subunit vaccines have a more complex manufacturing process, requiring the protein to be grown and purified in specialized cell cultures. However, they are highly stable and can often be stored at standard refrigerator temperatures. mRNA vaccines, while simpler in design, historically required ultra-cold storage conditions to prevent the delicate mRNA strands from degrading, though newer formulations have improved stability.