Universal flu vaccine candidate shows strong results—will it be the holy grail?

A candidate for a universal flu vaccine that could protect people against most strains of influenza has been identified by researchers at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

In a study published in Nature Communications, the authors wrote that the vaccine elicited a strong antibody response to the hemagglutinin (HA) stalk, a structure on the surface of flu viruses. Mice that were administered the vaccine were protected from various flu strains.

Each year, influenza infections cause tens of thousands of deaths in the United States alone, despite the widespread use of seasonal vaccines. Long considered to be one of the “holy grail” vaccines (along with a vaccine to prevent HIV infection), a universal flu vaccine could save countless lives across the world.

The newly described vaccine has the potential to be used in a similar manner as a tetanus vaccine: administered a few times throughout a lifetime for continual protection.  

“This vaccine was able to do something that most other candidate flu vaccines have not been able to do,” said study co-senior author Drew Weissman, MD, PhD, a professor of infectious diseases at Penn. “It was able to elicit protective responses against a conserved region that offers broad protection.”

In most modern viral vaccines, lab-grown viral proteins are used to elicit an immune response that protects people against future exposure. This approach has not had much success against influenza.

Flu virus particles feature mushroom-like HA proteins. Seasonal flu vaccines use these to elicit antibody responses, but the responses are almost entirely directed against the outermost “head” of the HA protein, which mutates rapidly. In addition, flu strains vary from season to season, and each strain may have different HA head structures. The resulting vaccines provide temporary, incomplete protection.

Instead of directly targeting HA proteins, the Penn vaccine uses mRNA molecules that encode HA proteins to elicit an antibody response. When injected, the RNA molecules are taken up by immune system dendritic cells and translated into copies of the HA protein by the protein-making machinery within those cells.

This production of viral proteins within the cell is better at mimicking a real flu infection, and it elicits a powerful protective antibody response.

“If it works in humans even half as well as it does in mice, then the sky’s the limit, “said co-senior author Scott Hensley, PhD, an associate professor of microbiology at Penn. “It could be something that everyone uses in the future to protect themselves from the flu.”

The strong antibody response included antibodies against the lower stalk region of the HA—a favored target for universal flu vaccines—as it does not vary among flu subtypes.

Seasonal vaccines typically do not elicit much of a response to the HA stalk. However, after two administrations of the Penn scientists’ mRNA vaccine 4 weeks apart, they noted a robust anti-stalk response in the mice.

Following immunization, the antibody responses persisted through the 30 weeks of the experiment. At the end of the study, the anti-stalk responses were stronger than at 4 weeks post-immunization. The experiments were also repeated in ferrets and rabbits.

Another vaccine that encoded the H1 subtype kept mice healthy when they were injected with otherwise lethal doses of three flu strains: the same H1 flu virus, a distantly related H1 flu virus, and an H5 strain.

“The next step is to test this in non-human primates and humans,” Dr. Hensley said.

An urgent need

The 1918 Spanish Flu outbreak killed between 50 and 100 million people worldwide, and Michael Osterholm, PhD, MPH, director, Center for Infectious Disease Research and Policy, University of Minnesota, argues that we are more susceptible to a similar pandemic. 

“Today, there are about 7.6 billion people on Earth, more than three times the population in 1918,” he said in an interview published in JAMA. “When we talk about less crowded living conditions today, that is true for part of the world. But for the vast majority of the world, it’s worse.”

Dr. Osterholm, author of the book Deadliest Enemy: Our War Against Killer Germs, also notes that the vaccines during the 2009 influenza pandemic were only 50% to 55% effective, and less than 1% of the world’s population had access to them during the first 6 to 12 months of the outbreak.

While he is optimistic that funding and research is finally being focused on development of a new flu vaccine, he states that the funding is far short of what it ideally should be.

Another barrier

An additional hurdle to implementation of a universal flu vaccine is less about the science and more about public acceptance.

While the current anti-vaccination movement tends to focus on childhood immunizations despite a preponderance of evidence to the contrary, there is an “anti-vax” movement around almost every vaccine created, according to Michael Kinch, PhD, associate vice chancellor and director of the Center for Research Innovation in Business at Washington University in St. Louis, MO, and author of Between Hope and Fear: A History of Vaccines and Human Immunity.

“It's becoming more expensive to develop vaccines and less profitable,” Dr. Kinch said in an interview with NPR. “We haven't developed a novel vaccine in decades. Pharmaceutical companies are abandoning vaccines. The anti-vax movement, I would argue, is stronger than ever. They're highly organized, highly motivated, and well-funded.”