Can We Make a Universal Pandemic Vaccine?

A Closer Look at Biden’s $5 Billion “Next Gen Project”: Part II

On April 10, 2023, the White House announced the creation of a $5 billion program in part to create newer, better coronavirus vaccines. Focusing on nasal spray vaccines and universal coronavirus vaccines, the program was called “Project Next Gen.” (Last week I addressed the nasal spray vaccines)

Wouldn’t it be nice to have a vaccine that protects against not only SARS-CoV-2 but all coronaviruses with the potential to cause a pandemic? One that protects against viruses like SARS-1 (which caused a small pandemic in 2003), MERS (which caused a small pandemic in 2012), as well as all the other coronaviruses that are now circulating in bats and other small mammals lurking in caves and forests throughout the world?  How hard could that be? Turns out, very hard.

I offer two cautionary tales: attempts to create a universal influenza vaccine that eliminates the need for yearly vaccination and an HIV vaccine to prevent AIDS.

Every year in the United States, influenza virus causes hundreds of thousands of hospitalizations and tens of thousands of deaths. And every year, the FDA Vaccine Advisory Committee picks the three or four strains of influenza that are likely to enter the country in the coming winter. The Committee is usually right, but not always; sometimes, it fails to pick the right strains. This happened twice during the previous ten years. As a result, more vaccinated people suffered and died from influenza during those two years than would have had the Committee picked the right strains.

The most important influenza virus protein, the one that attaches the virus to cells, is called the hemagglutinin, or HA, protein. The reason that we need a yearly influenza vaccine is that the HA protein (much like the SARS-CoV-2 spike protein) is constantly changing. It changes from year to year. It even changes during the winter season.

Although the HA protein from influenza is always evolving, many regions on the other 10 influenza proteins don’t change much; they remain relatively constant for all influenza strains. In fact, several regions on the HA protein also remain relatively constant. So, wouldn’t it make sense to make a vaccine directed against those conserved regions? The ones that don’t change much. Then we wouldn’t need a yearly vaccine; we would be protected against all influenza strains.

Researchers have been trying to do exactly that for the last 50 years. Unfortunately, we are no closer to a universal influenza vaccine now than we were 50 years ago.

Attempts to make an HIV vaccine, which began in the early 1980s, further demonstrate the difficulties of making a universal coronavirus vaccine. People who are infected with HIV rapidly make antibodies that neutralize the virus; those antibodies work well to eliminate the infecting strain. The problem with HIV is that the virus constantly changes during the infection; antibodies that work at the beginning of the illness don’t work as the illness progresses and the virus continues to evolve. HIV is the ultimate moving target.

The good news is that HIV, like influenza and SARS-CoV-2, has many regions on its 15 proteins that are highly conserved, and these regions don’t change during infection. Companies have now spent billions of dollars trying to make vaccines directed against these highly conserved regions—again, without success.

Our experiences with influenza and HIV vaccines should serve as cautionary tales for a vaccine that prevents all possible strains of coronavirus. But you never know. It is certainly worth trying. And the money provided by Project Next Gen will allow that effort to continue. And, as is true in all scientific endeavors, we might learn something that was completely unexpected.