January 16, 2018 |

PATH and partners exploring pathway to universal flu vaccine

A universal flu vaccine could help stop the cycle of both seasonal and pandemic influenza
Two lab technicians in protective gear handling eggs.
Lab technicians grow influenza virus for vaccines in chicken eggs. The development of a universal influenza vaccine could end our reliance on seasonal vaccination. Photo: PATH/Matthew Dakin.
  • PATH has ushered a universal influenza vaccine candidate into early stage clinical study.
  • The study relies on chimeric vaccine technology to overcome the ever-mutating virus.
  • PATH is partnering with several research centers including the Icahn School of Medicine at Mount Sinai, Cincinnati Children’s Hospital Medical Center, and Duke Clinical Research Institute to conduct the study.

You’ve heard of the flu shot, but how much do you really know about influenza?

Colloquially, we use the word “flu” whenever someone is feeling poorly; it has come to represent the common cold, stomach ailments, and more. Complicating matters is that many of us go on to suffer colds or other unrelated maladies after getting vaccinated—so it’s hard to understand what we’re being protected from and why the discomfort of vaccination is worth it.

But influenza is not a broad term for illness. It’s a serious disease with serious consequences.

And PATH is committed to tackling it with a vaccine that protects against all influenza.

An enduring threat

Globally, seasonal influenza results in three to five million cases of severe illness and up to 500,000 deaths each year. It spreads from person to person through coughing and sneezing, and it poses a particular risk to the elderly, the chronically ill, pregnant women, infants, and young children—all of whom are more likely to suffer complications or death as a result of infection. People in low-resource countries are also more likely to feel the effects of influenza due to underlying nutritional deficiency, untreated medical issues, and limited access to health care. What’s more, the virus has the potential to cause millions of deaths worldwide if a highly virulent pandemic strain were to emerge. Models estimate that in an influenza pandemic, 96 percent of deaths would happen in low-resource countries.

The most severe influenza pandemic on record, the 1918 “Spanish Flu,” infected up to 50 percent of the world’s population and caused 50 million deaths worldwide—something that could easily happen again, especially in today’s interconnected world.

A better vaccine

Vaccination is our best tool in the fight against influenza. But best doesn’t mean simple. Because influenza viruses are constantly changing into slightly different strains, infection or vaccination one year does not mean immunity the next. As such, influenza vaccines must be updated on an annual basis to keep up with currently circulating strains. Despite in-depth research and monitoring, it is not always possible to predict which strains will circulate, meaning, the flu shot is not always effective from year to year.

PATH is exploring new solutions: a vaccine that covers all strains and lasts across seasons—a universal influenza vaccine.

The development of one could eliminate the need to periodically adjust influenza vaccines to circulating strains, thereby creating a cost-effective and efficient way to protect people around the world.

PATH has partnered with the Icahn School of Medicine at Mount Sinai (ISMMS), Cincinnati Children’s Hospital Medical Center, and Duke Clinical Research Institute to conduct a study into chimeric hemagglutinin vaccine technology that could pave the way for future universal influenza vaccines.

Chimeric hemagglutinin technology—pioneered by ISMMS—hinges on the concept that engineering the structure of the influenza virus’s hemagglutinin (HA) molecule (a protein on the virus’s surface that facilitates entry into respiratory tract cells) can prompt an immune response against the portion of the virus that is similar across strains and across seasons—thereby negating the need for annual vaccination.

The HA molecule is shaped like a mushroom, with two distinctive parts: the head and the stalk. Both portions elicit an antibody response from the human body, but the head more so, a phenomenon referred to as immunodominance. This means that when people are either vaccinated against or infected by influenza, they produce more antibodies against the head region of the HA molecule than against the stalk region. This is troublesome because the head portion is what changes from season to season; the stalk, however, remains the same. Researchers posit that if they can prompt the body to focus its immune response on the stalk, the influenza vaccines will protect against more strains and for a longer amount of time.

To create a chimeric vaccine, the HA head is removed from the stalk of a currently circulating virus and swapped for the head of a virus that doesn’t typically infect humans. Unfamiliar heads are used because the body won’t have existing antibodies the vaccine can build upon, which decreases the immunodominance of the head region. Researchers hope this arrangement will force a stronger immune response against the stalk region, while the head region is relatively ignored.

It is no easy task, but preclinical research has shown this approach is the key to broad and long-lasting immunity against influenza. Despite the challenges facing a universal flu vaccine, solutions now seem within reach. A universal influenza vaccine could revolutionize prevention, access, and affordability, and save hundreds of thousands of lives every year.

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