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.
In February 2018, NIAID released its Universal Influenza Vaccine Strategic Plan outlining the institute’s research priorities. It focuses on three specific research areas to simultaneously broaden knowledge around basic influenza immunity and advance translational research efforts to drive universal influenza vaccine development by:
- Improving knowledge of transmission, natural history and pathogenesis of influenza infection to help understand factors that contribute to the spread, severity and diversity of influenza, and to identify measures to improve disease control.
- Characterizing influenza immunity and immune correlates of protection through the study of immune responses to natural influenza infection and vaccination over time that can be used to identify measurable immune factors critical to vaccine design.
- Supporting rational design of universal influenza vaccines through the development and iterative clinical testing of immunogens, adjuvants, diverse platforms, and alternative vaccine delivery methods. NIAID will continue to build resources (Box 1) to lay the foundation of knowledge needed to answer fundamental questions in these research areas and to test new products. These resources will provide the building blocks critical to attaining the research area objectives outlined in the plan with an ultimate goal of rationally designing next-generation influenza vaccines.
Achieving these goals will require a global collaborative effort among government agencies, industry, philanthropic organizations, and academia that incorporates interdisciplinary approaches and new technological tools, such as gene-based vaccination, to aid in the development of vaccine candidates.
Leading Vaccine Strategies and Candidates
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.
In May 2018, NIAID launched a Phase 2 clinical trial of a universal influenza vaccine called M-001. The vaccine, which was developed and produced by BiondVax Pharmaceuticals based in Ness Ziona, Israel, contains antigenic peptide sequences shared among many different influenza strains.