The Lancet Infectious Diseases
The 2017–18 influenza season in the northern hemisphere was notably intense, similar to the immediately preceding season in the southern hemisphere. A likely factor influencing the intensity of these seasons was the effectiveness of the influenza vaccine both in terms of the matching of the components of the vaccine to the dominant circulating strains and the ability of these individual components to elicit protection. A universal influenza vaccine, which would offer broad and long-lasting protection, would overcome the shortcomings of the current cat-and-mouse approach.
Coinciding with the waning of the influenza season in the northern hemisphere, the US National Institute of Allergy and Infectious Diseases (NIAID) published its strategic plan for the development of a universal influenza vaccine. The development of such a vaccine has been made one of NIAID’s highest priorities and the plan lays out the broad interdependent advances needed to realise this ambition. The NIAID criteria for a universal vaccine will certainly be challenging to meet. The vaccine, according to the plan, should be at least 75% effective against symptomatic infection, should protect against group I and II influenza A viruses, should offer durable protection that lasts at least a year but preferably multiple seasons, and should be suitable for all ages.
The plan focuses on three research areas: understanding transmission, natural history, and pathogenesis; characterisation of immunity and correlates of immune protection; and rational design of the vaccine. NIAID stresses that each area is of equal priority and advancement in any of these areas will go hand in hand with advancement in the others. These research areas are subdivided into broad objectives, offering signposted steps towards the ultimate goal.
However, despite the advances in influenza research made so far, the plan shows that most of the journey towards a universal vaccine still lies ahead. NIAID says that development of this vaccine is more feasible now than it was a decade ago. But it is also made clear that the understanding of many fundamental questions is poor. For example, the very first objective opens unequivocally with “our understanding of transmission of both seasonal and pandemic influenza is inadequate“—a frank admission that reveals the scale of this undertaking.
The impact of a universal vaccine on the enormous burden of seasonal influenza is only half the story, despite the toll being from 3 million to 5 million severe cases worldwide per year, which includes from 300 000 to 500 000 deaths. Authorities are also highly concerned by the risk of pandemic influenza. The difficulty in the case of pandemic strains stems from the fact that they emerge unpredictably and therefore make it impossible to produce and stockpile an appropriate strain-specific vaccine. An influenza pandemic, in this scenario, would inflict large-scale damage long before a vaccine was available. So, hypothetically, a universal vaccine would eliminate the need for a hurriedly prepared stockpile since the emergency response would be to distribute the existing universal vaccine. Additionally, much of the population would already be protected from the pandemic strain given the universal nature of the vaccine.
The ambition of producing a universal influenza vaccine has been around for a long time. But initial optimism faded when the enormity of the task started to become clear. For example, the search for a universal antigen that elicits protection has proved elusive. NIAID’s formalised plan does not make the task any less daunting but does provide structure around which collaborative efforts can be built. A future with a universal influenza vaccine is certainly imaginable but, given the scale of the efforts still needed, it is not likely to happen soon. But every step forward will yield information that can be used to reinforce current vaccination efforts, so the potential for a better influenza vaccine or approach to vaccination in the nearer term might be very realistic.
Although this infection is often trivialised as just “the flu”, when it is tamed the world might begin to appreciate the substantial burden that was taken for granted. To reach this goal, despite the technical aspects that form the core of the plan, the most significant step is stated in the concluding sentence which recognises that success will best be achieved through collaboration across disciplines and across nations.