To thwart flu pandemics, we need to decode the human immune system

Last year was Australia’s worst for flu since 2009. During the winter of 2017, which ended in August, there were 2.5 times more cases of influenza than in 2016, along with twice as many flu-related hospitalizations and twice as many flu-related deaths. This presaged the current influenza season in the Northern Hemisphere, which is on pace to be one of the worst in recent years. In addition, a simmering outbreak of an avian flu virus in China has killed 39 percent of nearly 1,600 persons infected since 2013. Those are two ominous signs as we mark the centennial of the greatest influenza outbreak in history, the 1918 flu pandemic that killed an estimated 50 million people around the world.

Public health experts have traditionally fought skirmishes against influenza. We believe that the time has come to mount an all-out assault on it by decoding the human immune system.

Every year, by tracking sentinel outbreaks throughout the world, public health officials try to stay one step ahead of influenza by developing a vaccine that will counter that season’s strain. Yet even when the vaccine formulation hits the mark, it still confers protection in only about 60 percent of those who receive it. And it is often even less effective for those most at risk for influenza-related complications: young children, pregnant women, the elderly, and those with compromised immune systems.

History has repeatedly taught us that attempting to predict the next influenza pandemic, or chasing after potential pandemic outbreaks, can be both costly and ineffective. The primary reason that influenza vaccines aren’t more effective, and the reason they can’t generate broadly protective, long-lasting immunity in everyone, is that vaccines are thwarted by an entity we don’t yet fully understand: the human immune system.

Make no mistake: Vaccines are among the most effective public health interventions in human history, second only to clean drinking water in the magnitude of their impact. They have led to the global eradication of one infectious disease, smallpox, and the near-eradication of polio. Vaccines have reduced death and disability caused by many infectious diseases, including measles, mumps, rubella, chickenpox, diphtheria, tetanus, and whooping cough. The vaccine against hepatitis B has reduced the incidence of liver cancer; those for human papillomavirus have done the same for cervical cancer.

But the full potential of vaccines remains just outside our reach. Some require multiple immunizations; others are less effective in the populations that need them the most, such as influenza vaccines in the elderly and diarrheal vaccines in the developing world. Vaccines against HIV, tuberculosis, and malaria still elude us, as these complex pathogens have developed mechanisms to evade the immune system that continue to impede vaccine developers. And we remain threatened by new and emerging infectious diseases such as Ebola and Zika, which will inevitably outpace the lengthy process of vaccine research and development, resulting in uncontrolled epidemics and leaving us woefully unprepared for the next global pandemic.

As recently as 2009, the world faced an influenza pandemic caused by what was, fortunately, a mild strain of influenza virus. By the time a vaccine was available specific to the strain, the flu had already spread to every continent, and was past its peak in North America. Had this strain of the influenza virus been severe, the outcome could have been catastrophic, mimicking the great pandemic of 1918.

Science is now poised to change all that. In the not-too-distant future, we predict that researchers will be able to harness the human immune system to prevent and control disease in ways previously considered unimaginable: one-shot vaccines that offer lifelong protection in everyone; a universal influenza vaccine that protects against seasonal and pandemic outbreaks of flu; vaccines against currently intractable infectious diseases; and, one day, vaccines against noninfectious chronic diseases, everything from cancer to heart disease and Alzheimer’s disease.

Decoding the human immune system holds the key to the development of such new and improved vaccines. Deciphering the human immunome, the universal and common elements of the B and T cell receptors that make up the adaptive immune system, will facilitate germline targeting and structure-assisted vaccine discovery. Understanding the mechanisms for protective immunity will enable rational vaccine design aimed at specifically inducing such immune effector mechanisms.

This is finally possible because of the convergence of technological advances across biomedical, computer, and engineering sciences, including the enhancement of artificial intelligence and machine learning capabilities to analyze and interpret unprecedented quantities of data. In the same way that the Human Genome Project transformed biomedical research and enabled the genesis of personalized medicine, and the Hubble Telescope transformed planetary sciences and our understanding of the universe, decoding the human immune system has the potential to revolutionize 21st century global health, ushering in new advances in diagnostics, vaccines and therapeutics.

It won’t be cheap, and it won’t be easy. Decoding the human immune system will take a decade of research and cost more than $1 billion. It will require innovative public-private partnerships working collectively to decipher the common components and rules of human immunity. But the return on investment — a blueprint for how the immune system fights disease — will be extraordinary and applicable to all facets of human health.

Deciphering how the human immune system combats disease is one of the greatest frontiers of science, and is now within reach. If society grasps this unprecedented opportunity, commits resources to it, and facilitates creative new models for working together across multiple scientific disciplines, we can not only eliminate the threat of pandemic influenza but reshape how we approach all life-threatening diseases.

Wayne C. Koff is president and CEO of the Human Vaccines Project in New York. Peter C. Doherty is a Nobel Laureate professor of microbiology and immunology at the University of Melbourne. Margaret A. Hamburg is the foreign secretary of the National Academy of Medicine in Washington, D.C., and a former FDA commissioner.