A nanoparticle-based flu vaccine discovered and developed by the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), was manufactured by Frederick National Laboratory (FNL) for a Vaccine Research Center Phase 1 clinical trial. The vaccine was found to be safe, well-tolerated, and immunogenic against multiple flu subtypes and, with further development, might provide broader, longer-term protection than conventional once-a-year flu shots -- a potential step toward a universal flu vaccine.
FNL’s Vaccine Clinical Materials Program manufactured the vaccine product in 2016, releasing the product and delivering it to NIAID for clinical trials in 2017.The nanoparticle vaccine can be produced more rapidly than conventional protein-based flu vaccines, so it can quickly be targeted to circulating strains of influenza. It may also be useful in pandemic response, according to a scientific and clinical team led by Julie Ledgerwood of the NIAID Vaccine Research Center. Results of their clinical trial were reported in Nature Medicine, and follow-up research is under way.
Annual flu vaccines focus on a few strains anticipated to circulate during an upcoming season. Many of the vaccines are developed in chicken eggs, a process that takes up to six months to complete. These annual shots trigger an immune response to parts of the virus that are easy targets for the vaccine, proteins that extend from the vaccine surface like flowers on the end of a stem. But these proteins regularly mutate so vaccines must be reformulated every year.
As an alternative, the research team developed a nanoparticle platform using a ferritin protein that self-assembles into a scaffold upon which they can affix viral proteins that elicit an immune response to the H2 subtype of influenza.
The trial enrolled 50 healthy volunteers 18 to 70 years of age. Those 18-to-47 years old were assumed to have been unexposed to the H2 subtype of influenza, which has not circulated in the United States since 1968 before they were born.
Those 52-70 years old were considered to have been “H2 exposed.” The combined population gave researchers a chance to assess the vaccine in two groups: people who may have some immunity to the H2 flu subtype and others would have no such immunity. It is important to test both groups because any future universal flu vaccine must overcome barriers posed by preexisting immunity from circulating strains, the scientists said.
In both groups, the vaccine was safe and well-tolerated. Both study populations developed antibodies against influenza, including antibodies directed at the stem region of the virus, which does not mutate as actively as the “head” region. This suggests that the nanoparticle vaccine might provide broader, more lasting protection than current seasonal flu shots.
The Phase I clinical trial demonstrated “a proof of concept for a new generation of vaccines that display orderly arrays of antigens on self-assembling nanoparticles,” the scientists wrote. “Owing to the breadth of response induced, these results indicate a potential use for this ferritin nanoparticle-based antigen display platform in pandemic vaccine preparedness and for universal influenza vaccine development.”