Seasonal outbreaks of the flu cause thousands of deaths even in a good year, and the last flu season, 2017-2018, was a terrible one. It killed 80,000 Americans and sent 900,000 to the hospital, making it the worst influenza season in decades.
Data from the Centers for Disease Control and Prevention (CDC), show how much of an outlier it was: Previously, seasonal outbreaks since 2010, had killed between 12,000 and 56,000 and caused between 140,000 and 710,000 hospitalizations.
Statistics like that can seem impersonal, but this one isn't: "One hundred and eighty families put a child in a grave last year because of a vaccine-preventable infection," according to Wendy Sue Swanson, a pediatrician at Seattle Children's Hospital. Eighty percent of them had not had a flu shot.
Vaccination is the key to prevention. According to estimates from the CDC, in six flu seasons starting in 2005-06, flu vaccination against a variety of strains prevented almost 14 million cases.
That might seem impressive, but our current vaccination rates are unacceptably low – in large part because of the proselytizing of anti-vaccine activists – and in some years the available vaccines are barely adequate. Vaccine exemption rates – most often for "philosophical objections" to vaccination – among infants and school-aged children have been rising, creating pockets of unimmunized, vulnerable individuals, according to just-published data from the CDC.
This is inexcusable. "Not only does it put at risk those who choose to forego vaccination, but also people who cannot be vaccinated because they're younger than six months or have medical contraindications, such as an impaired immune system," according to pediatric allergist Dr. Michael H. Mellon.
Too many vaccinated people still get the flu, and when it comes to research funding to address this problem, our public health agencies seem little exercised about it.
We know a lot about the flu virus and humans' immune responses to it. The surface of flu viruses is studded with proteins called hemagglutinins, which are the part of the virus that binds to cells in a person's respiratory tract, initiating infection. Hemagglutinins are shaped a bit like a lollypop – they have a globe-like head attached to a stalk.
When the immune system is exposed to a flu hemagglutinin protein – either on a virus or in a vaccine – it produces antibodies to the protein. Most of those antibodies target the head of the protein, which is the part that mutates continuously and, thereby, evades the immune system's defenses.
Conversely, the stalk doesn't undergo as much change and is quite similar from strain to strain. Antibodies that recognize and neutralize the hemagglutinin stalk should, in theory, work against multiple strains of flu. However, the stalk doesn't elicit a strong immune response, and researchers have not yet found a way to enhance it.
Because flu viruses mutate frequently, vaccines are reformulated early in the year as a mixture of virus strains predicted to prevail during the next fall and winter. Depending on how good the selections of strains are, during a given flu season the effectiveness can vary widely.
Since the 2004-05 season, vaccines' effectiveness has varied from 10 to 60 percent. Last season, the vaccine was a poor match for circulating viruses, and was around 40 percent effective overall, but lower in the elderly. In part, that was because most illnesses were caused by a virulent strain called H3N2, against which flu vaccines typically aren't very effective.
One of the reasons for flu vaccines' relative ineffectiveness last season was that most were prepared from fertilized chicken eggs, a method of production known to reduce the effectiveness against certain flu strains, particularly H3N2. Manufacturers should stop using chicken eggs and instead prepare vaccines by growing virus in "cultured cells" – cells that have been removed from animals and are grown under controlled conditions.
That method would produce vaccines with greater fidelity to the targeted flu strains. Many U.S.-licensed vaccines are already produced this way, such those for rotavirus, polio, smallpox, hepatitis, rubella and chickenpox, plus at least two flu vaccines. Thus, regulators should require manufacturers to phase out flu vaccines produced with inferior, 70-year-old technology.
However, the holy grail of flu vaccines would be a "universal" vaccine that recognizes all strains, including newly-arising ones. Several different approaches are being pursued, but significant challenges remain. As noted above, the major difficulty is that the most immunogenic part of the flu virus – the hemagglutinin proteins on the surface of the virion– is the part that mutates, or drifts, from year to year, which is why vaccines need to be constantly updated. (That contrasts with the vaccines for other viral diseases such as measles and mumps, which confer long-standing immunity.)
In spite of the importance of research on universal vaccines and the variety of approaches, there is surprisingly meager federal research funding in this area. Michael T. Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy, and writer Mark Olshaker tracked the government's investment in universal flu vaccine research: "The National Institutes of Health has publicly declared developing a [universal] vaccine a priority, [but] it has only about $32 million this year specifically for such research."
Another federal agency, the Biomedical Advanced Research and Development Authority, is spending $43 million on a single project in pursuit of "game-changing influenza vaccines."
These are meager efforts when compared to the roughly $1 billion spent annually on developing an HIV vaccine and the many billions that have been spent on vaccines for the Zika and Ebola viruses, which have little relevance to Americans.
We also need more research on vaccine additives called "adjuvants," chemicals mixed with the viral antigens to further boost the immune response.
Within the population, a vaccine's effectiveness varies widely because it is affected by the general health and age of the recipient. Although people 65 and older make up only 15 percent of the U.S. population, on average they account for about 60 percent of the hospitalizations and 90 percent of the deaths attributed to seasonal flu. Seniors respond less well to vaccines than younger people because, as we age, our immune system functions less well. Scientists at the National Institutes of Health, after reviewing 31 vaccine response studies comparing groups of different ages, called for more potent formulations for the elderly.
But exactly how strong the shot should be, and whether additional injections would boost immunity, requires more study. There is currently a flu vaccine for people over 65 that contains four times as much antigen as regular flu shots, and one that contains an adjuvant, but those tweaks have improved effectiveness only marginally.
An increase in research funding on adjuvants, more effective dosing regimens (especially for seniors), and better production methods are achievable changes that would better prepare us to face flu outbreaks.
In the meantime, an easy and much-neglected intervention would be for public health officials and the media to make the public more aware of the currently available anti-flu medications, Tamiflu, Relenza, and Rapivab, that can both prevent the flu and also shorten the duration and severity of the illness, should it occur. The development of a universal vaccine is more challenging but it promises much greater results, and deserves more support.
The fearsome 2017-2018 flu season should serve as a wake-up call: On several research and public health fronts, we need to redouble our efforts to prevent and treat the flu, especially via the development of improved vaccines. In the meantime, get a flu shot every year.
Henry I. Miller, a physician, molecular biologist, and former flu researcher, is a Senior Fellow at the Pacific Research Institute. He was the founding director of the FDA's Office of Biotechnology.