NIAID Announces Plan to Make Universal Flu Vaccine A Reality

As the United States continues to struggle with flu this season and more reports come in stressing the low efficacy of the seasonal flu vaccine, the National Institute of Allergy and Infectious Diseases (NIAID) has revealed its strategic plan for the development of a universal vaccine.

The development of a universal flu vaccine, a vaccine capable of providing durable protection for all individuals, in all age groups, against several strains (including those that might cause a pandemic), is a goal that has been long sought after. Now, the NIAID has made the development of such a vaccine “one of its highest priorities,” according to a press release put out by the institute.

When it comes to the seasonal flu vaccine, effectiveness can range anywhere from 10% to 60%. However, these vaccines “provide virtually no protection against novel pandemic strains,” according to NIAID. Regardless of whether it’s seasonal or pandemic flu, the best protection lies in strain-specific vaccination, and therefore, the institute states that vaccines that “are more broadly and durably protective are needed.”

To this end, the NIAID has released a research plan to develop a universal flu vaccine, using information gleaned from a workshop which convened scientists, industry, and government officials in June 2017 to identify criteria for such a vaccine and define any knowledge gaps that exist, in order to bring the vaccine to fruition.

The team concluded that a universal flu vaccine should:

• Be at least 75% effective against symptomatic influenza infection
• Protect against group I and group II influenza A viruses (influenza B would be a secondary target)
• Have durable protection that lasts at least 1 year and preferably through multiple seasons

The plan outlines activities that will address gaps in 3 major research areas:

1. Transmission, natural history, and pathogenesis studies utilizing prospective cohorts
2. Influenza immunity and correlates of immune protection
3. Strategies in rational vaccine design to elicit broad, protective immune responses

The first research area was identified because insufficient understanding of flu transmission, natural history, and pathogenesis have hindered vaccine improvements. “Collection of clinical, immunologic, and virologic data from clinical cohorts along with comprehensive standardized assays will be vital in understanding the evolving immune response to influenza and how repeated exposure to influenza viruses and vaccines shapes it,” the authors of the plan write. In order to inform more effective strategies for universal vaccine design, investment needs to be made in basic research. Studies will work to better understand flu transmission, identify factors that impact disease severity, and expand characterization of circulating flu viruses.

The next research focus has to do with immunity; universal vaccine strategies strive to induce broadly protective immunity, but the fact that flu viruses are able to undergo antigenic drift makes it harder to achieve that goal. “The role of T-cell mediated immunity in influenza infection and disease has historically received little research attention; however, it may offer another pathway to achieve broad protection,” the authors suggest. Furthermore, inducing strong CD8+ T cell responses may need to be incorporated into universal flu vaccine strategies in order for the “immune response to be fully successful.” In this area, the plan is to improve understanding of host response to infection/vaccination; to delineate innate and adaptive immune response to natural infection and vaccination; to identify mechanisms of protection beyond HAI; and to standardize/harmonize non-HAI assays.

As for the last focus research area, to support rational design of these vaccines, the NIAID stresses that the vaccine “must capitalize on knowledge gained by assessment of the protective immune correlates elicited by natural infection and seasonal vaccination, and by experimental vaccine formulations (including adjuvants) and prime-boost regimens to rationally advance vaccine designs that maximize antibody- and cell-mediated immune responses.” Therefore, a “coordinated, iterative” approach needs to be taken. Objectives of research in this area will work to design new immunogens to widen breath of protection; to test adjuvants and delivery methods; and to test candidates in iterative phase 1/2 trials.

In order to advance all research areas, the NIAID will launch “a multidisciplinary consortium” of scientists and coordinate activities that will bring us that much closer to the goal of a universal flu vaccine.

“Developing an influenza vaccine that improves the breadth and durability of protection against seasonal influenza and provides protection from pandemic strains is a high scientific priority for NIAID,” the authors write. “NIAID will accelerate its efforts for developing a universal influenza vaccine by supporting a consortium of scientists focused on addressing obstacles that have limited progress toward this goal.”