The National Institutes of Health (NIH) has announced the initiation of a phase I clinical trial for an mRNA-based flu vaccine aimed at providing long-lasting protection against a wide range of influenza viruses. This development marks a significant milestone in the quest for a universal flu vaccine, leveraging the remarkable success of the mRNA vaccine platform. Currently, healthcare systems worldwide combat the seasonal flu by administering vaccines that need to be reformulated annually to match circulating strains. However, the constant evolution of the virus poses challenges, as even well-matched vaccines require individuals to receive a new shot each year.
Hugh Auchincloss, acting director of the NIH’s National Institute of Allergy and Infectious Diseases highlighted the significance of a universal influenza vaccine being developed. This could potentially eliminate the need for yearly development of seasonal flu vaccines as well as patients having to get a flu shot every year. Moreover, he emphasized that it could serve as a vital defense against future flu pandemics since certain strains have significant pandemic potential.
Developing a successful universal vaccine has proven elusive. Current flu vaccines primarily target rapidly evolving components on the outside of the virus particles, namely the hemagglutinin (Ha or H) and neuraminidase (Na or N) proteins. These proteins, resembling lollipops attached to the virus particle, facilitate viral entry and exit from human cells during infection. However, the NIH researchers working on the universal vaccine have focused on a different part of the Ha protein—its stem. This stem region is highly conserved and evolves more slowly than the tops of the proteins. Antibodies that target this conserved region can potentially recognize Ha proteins from various flu strains within the same class, providing long-term immunity. The mRNA-based vaccine incorporates a segment of genetic code in the form of mRNA, enabling human cells to produce this conserved stem region and trigger an immune response against it.
Promising data has already been obtained from a similar vaccine design that targeted the Ha stem using stabilized protein fragments attached to a nanoparticle. In a phase I trial, this vaccine was deemed safe and effective, inducing cross-reacting neutralizing antibodies against influenza viruses in the same virus group (H1). Moreover, these neutralizing antibodies persisted for over a year after vaccination. The mRNA-based vaccine will now undergo a small trial involving 50 participants recruited through partners at Duke University. Three groups of 10 volunteers will receive different vaccine doses to determine the optimal dose. Subsequently, an additional 10 individuals will be vaccinated, and their responses will be compared to a control group of 10 people who will receive the standard annual flu vaccine.
By employing multiple vaccine platforms, researchers aim to increase their chances of developing a successful universal flu vaccine. The ongoing phase I trial of the mRNA-based vaccine represents a significant step forward in the pursuit of enhanced flu protection that transcends annual reformulation requirements.