Three-dimensional structural depiction of the influenza hemagglutinin (HA) protein. The head (left) and stalk (right) can be seen here.
The influenza virus causes annual epidemics, which result in millions of cases of severe illness worldwide. High-risk groups, including pregnant women, the very young or elderly, and chronically ill individuals, are more likely to experience complications from influenza infection, such as pneumonia or bronchitis. Current influenza virus vaccines are effective, but they must be reformulated and administered annually to target the influenza virus strains predicted to circulate each year.
To address these issues, NIAID is supporting research to promote the development of universal influenza vaccines, which would provide broader protection against multiple strains of influenza viruses. In 2018, NIAID published a strategic plan for addressing the research areas essential to creating a safe and effective universal influenza vaccine.
One important objective outlined in the strategic plan is the design of new vaccine targets common across multiple influenza strains. Influenza vaccines train the body's immune system to induce antibodies that target the viral protein hemagglutinin (HA), which is important for virus entry into host cells. This protein is made up of a head and a stalk domain. Most antibodies elicited by vaccines target the head domain, but some antibodies do target the stalk. Antibodies to the head domain typically can only identify a specific head domain shape or structure and since the head domain can vary widely between different virus strains and is subject to genetic changes with time, new vaccines specific to the most common strains are required annually. However, the stalk domain of the HA protein is more constant, or conserved, when compared among different virus strains, allowing for the possibility of a more broadly protective vaccine.
NIAID has been supporting a universal vaccine strategy which uses vaccine constructs that are made of combinations of conserved HA stalk domains with variable HA head domains derived from different virus strains. Sequential vaccination with these constructs allows an enhanced antibody response to form against the conserved stalk; these antibodies have been shown to provide broader protection against many influenza virus strains.
NIAID has provided support for this universal influenza vaccine strategy, allowing the work to advance from basic research and proof-of-concept studies in animals through clinical development. This work has facilitated major advances in the development of a universal influenza vaccine.