In pharmacies all over the nation, the same custom is carried out each fall. People roll up their sleeves, put up with a minor sting, and leave with faith that this year’s flu shot will work. It could. Perhaps it won’t. The virus continues to spread, as it usually does.
Xiu-Feng “Henry” Wan, a virologist at the University of Missouri, is driven into his lab most mornings by this uncomfortable reality. Wan oversees the NextGen Center for Influenza and Emerging Infectious Diseases in Columbia, which recently finished a significant expansion that doubled the center’s research capacity by adding more than 17,000 square feet of biocontainment space. You get the impression that the work being done there operates on a different scale than the typical yearly flu update when you walk through a facility like that, past sealed hallways and climate-controlled chambers designed to replicate tropical and temperate environments.
Wan’s team may be onto something truly important, according to the science they recently published in Nature Communications. Instead of letting the immune system focus on the parts it is already familiar with, the study presents a vaccine strategy that targets particular structural regions of the influenza virus’s surface protein, known as epitopes. It turns out that this obsession is a major factor in the rapid decline in the effectiveness of yearly flu shots. The immune system’s pre-existing memory turns into a liability rather than an asset when the familiar aspects of the virus change even slightly. It reacts to what it recalls rather than what is truly present.
According to Wan, it involves retraining the immune system’s focus. The method basically teaches immune cells to coordinate differently—to cast a wider net—by incorporating several different versions of these epitopes in the vaccine model. Additionally, some of the targeted areas change less over time than others because they are more stable. Researchers looking for a universal flu vaccine have been pursuing that stability for years. Although it’s still unclear if this approach will work well in human trials, the preliminary findings suggest a direction that is difficult to rule out.
All of this is part of a larger goal. In 2019, Wan moved to Mizzou in part due to the university’s uncommon willingness to allow researchers from veterinary science, engineering, medicine, and agriculture to collaborate in real proximity.
What is studied here is shaped by this cross-disciplinary setup. Wenjun Ma, a colleague, is working on vaccines that target highly pathogenic avian influenza, the strains that circulate among wild bird populations and cause quiet concern among public health officials. Another researcher at the center, John Driver, is mapping which immune cells react most strongly to influenza infection using single-cell RNA sequencing. These are not independent, parallel projects operating in silos. They are intended to educate one another.
Any virologist will tell you that wild flocks are an important issue. Influenza strains are transported across continents by migratory birds, which occasionally combine genetic material to create something the human immune system has never seen. The emergence of new variants can be accelerated by incomplete responses to those strains in humans or animals. Partial containment measures might not be sufficient, and they might even create selective pressure that accelerates mutation, as Wan has publicly pointed out. It’s a sobering idea that explains why a lab in mid-Missouri is investing a lot of money in climate chambers that can replicate the environments in which flu viruses truly reside and proliferate.
A world free of the flu is Wan’s long-term objective, expressed simply and without much fanfare. He admits that years of research are still needed to develop individualized vaccines, which are shots tailored to a person’s immunological history and risk profile. Scalability and cost are still significant challenges. However, the NextGen Center’s foundational work is gradually approaching that goal. It’s the kind of research that, for the first time in a long time, makes the yearly autumn ritual seem as though it might eventually become unnecessary, regardless of whether the epitope-targeting approach becomes a cornerstone of that future or just one promising chapter in a longer story.
