Universal Influenza Vaccine Research

A key focus of NIAID’s influenza research program is developing a universal flu vaccine, or a vaccine that provides robust, long-lasting protection against multiple subtypes of flu, rather than a select few. Such a vaccine would eliminate the need to update and administer the seasonal flu vaccine each year and could provide protection against newly emerging flu strains, potentially including those that could cause a flu pandemic.

Flu viruses are classified by two proteins on the outer surface of the virus: hemagglutinin (H) and neuraminidase (N). There are 18 different H subtypes and 11 different N subtypes, and viruses can be further broken down into different strains within those subtypes. For example, there are various strains of H1N1 influenza virus. The H protein (also called HA) enables the flu virus to enter a human cell. It is made up of a head and a stem. Seasonal flu vaccines fight infection by inducing antibodies that target the HA head. This region varies season to season, which is why flu vaccines must be updated each year. However, scientists discovered the stem typically remains unchanged, making it an ideal target for antibodies induced by a universal flu vaccine.

NIAID is studying various strategies to create a vaccine that elicits antibodies targeting the HA stem. For example, NIAID scientists designed an experimental vaccine featuring the protein ferritin, which can self-assemble into microscopic pieces called nanoparticles, as a key component. The vaccine showed promise in animal testing and is being evaluated for future trials in humans.

In another approach to a universal flu vaccine, NIAID scientists developed a vaccine incorporating four subtypes of the H protein into one vaccine. The vaccine is made from non-infectious virus-like particles that stimulate an immune response but cannot replicate or cause disease. Results have been promising in animal studies and may advance to human trials.

NIAID Vaccine Research Center scientists have initiated Phase 1/2 studies of a universal flu vaccine strategy that includes an investigational DNA-based vaccine (called a DNA “prime”) followed by a licensed seasonal influenza vaccine (“boost”) to improve the potency and durability of seasonal influenza vaccines. 

Content last reviewed on June 7, 2017