How mRNA and Protein-Based COVID-19 Vaccines Work

In "How mRNA and Protein-Based COVID-19 Vaccines Work," Dr. Curlin walks through how mRNA and protein-based COVID-19 vaccines each train the immune system.

Dr. Jeff Goad asks Curlin to walk through the COVID-19 vaccines currently available, setting up a discussion of how pharmacists might match specific products to specific patients. Curlin explains that the available vaccines fall into two broad categories: mRNA vaccines and protein-based vaccines. Pfizer and Moderna each make an mRNA vaccine, he says, while Novavax's protein-based vaccine is distributed through a partnership with Sanofi. All three vaccines target the same viral component, Curlin notes, but they deliver that target to the immune system differently.

Curlin describes the mRNA mechanism in detail. The vaccine's genetic material, carried inside a lipid nanoparticle, is injected into the arm and taken up by antigen-presenting cells and muscle cells. Those cells then use the RNA's instructions to manufacture the spike protein themselves. Antigen-presenting cells display that self-made protein to the immune system, training it to recognize the real virus later. The RNA itself degrades within days, Curlin emphasizes. It never becomes DNA, never integrates into the genome, and does not persist in the body. He adds that the lipid nanoparticle carrying the RNA also functions as its own adjuvant, helping prompt a stronger immune response.

The protein-based vaccine works differently, Curlin explains. It delivers a preformed spike protein directly, rather than instructing cells to manufacture it. Because protein alone is only weakly immunogenic, manufacturers add a saponin-based adjuvant to boost the immune response, achieving an effect similar to the mRNA platform's built-in adjuvant. Curlin also discusses mNEXSPIKE, Moderna's newer vaccine, which narrows its target to the regions of the spike protein believed most relevant to immune protection. Whether that more targeted approach improves real-world protection remains an open question, Curlin says, and side-effect profiles are not expected to differ meaningfully. He expects clearer answers as real-world data accumulates over the next year or two.

Up next, in "Vaccine Messaging That Resonates With Hesitant Pharmacy Patients," the conversation shifts to the specific messages that resonate with hesitant patients at the counter.