Before routine vaccines were developed in the 1900s, many children did not survive to adulthood and many adults did not reach old age. People succumbed in large numbers to diseases such as whooping cough and measles. Through the implementation of routine vaccination, many more children now reach adulthood and can contribute to society. Although some childhood diseases are for the most part relegated to history, the viruses responsible still sporadically cause outbreaks in unvaccinated populations.
This year in Texas, for example, a measles outbreak resulted in 762 infections, 99 hospitalizations and 2 deaths between January and August. Of those infected individuals, 718 were unvaccinated — including the 2 people who died. Moreover, outbreaks of other diseases for which vaccines exist still occur every year. For example, there were 40 million cases of flu and 28,000 deaths in the United States during the 2023–2024 flu season.
Nature Spotlight: Influenza
To strengthen the health of people in the United States, vaccination is essential. In particular, investment in the development and implementation of innovative vaccine technologies is urgently needed.
This is perhaps best illustrated by flu vaccines, which are still produced using technology developed in the 1960s. These vaccines have significant limitations. Their efficacy, which is calculated as the reduction in the number of people seeking medical attention owing to flu infection, ranges from 20–60% year to year, according to the US Centers for Disease Control and Prevention. One major reason for this unimpressive showing is that influenza viruses continually mutate to evade existing vaccine- or infection-induced immunity. To remain efficacious, therefore, vaccines need to be updated every one or two years. Predicting which strains will circulate during the next flu season is complicated, and sometimes strains are selected that are not a good match for the strains that people will be exposed to.
The second important limitation is that most influenza vaccines are formulated to be delivered as an injection in the arm. Administering a vaccine in that way induces an immune response that protects internal parts of the body, such as the lungs, but not one at mucosal surfaces such as the nose and throat. As a result, in-arm influenza vaccines reduce how sick people get and protect against death, but do not reliably prevent infection and have a limited ability to prevent transmission1.
To prevent infection and viral transmission, immunity must be induced in the nose and throat. To induce immunity here, a live-attenuated influenza vaccine (called FluMist) that is administered in the nose has been developed and licensed. Owing to the high degree of attenuation required to ensure safety, however, this vaccine has limited efficacy compared with in-arm vaccinations.
New vaccines that target the nose and throat are therefore needed. However, the immune system here is understudied; researchers do not fully understand how to induce protective immunity in this part of the body. The nose has two key attributes that render it difficult to use as a point of vaccine delivery. It’s designed to quickly remove foreign materials trapped in the mucus layer. And it is naturally tolerant of foreign material — the immune system marshals a response only when it recognizes signals, carried by foreign materials such as viruses, as dangerous.
Action needed
These obstacles are surmountable. Developing a more efficacious influenza vaccine in the United States will require four action points.